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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01231620
Registration number
NCT01231620
Ethics application status
Date submitted
28/10/2010
Date registered
1/11/2010
Titles & IDs
Public title
A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza
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Scientific title
A Phase III International, Randomized, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of 300 mg or 600 mg of Intravenous Zanamivir Twice Daily Compared to 75 mg of Oral Oseltamivir Twice Daily in the Treatment of Hospitalized Adults and Adolescents With Influenza
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Secondary ID [1]
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114373
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Universal Trial Number (UTN)
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Trial acronym
ZORO
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Influenza, Human
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Zanamivir
Treatment: Drugs - Placebo to match zanamivir
Treatment: Drugs - Oseltamivir
Treatment: Drugs - Placebo to match oseltamivir
Experimental: Intravenous (IV) Zanamivir 300mg Twice Daily - 300mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Experimental: Intravenous (IV) Zanamivir 600mg Twice Daily - 600mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Active comparator: Oral Oseltamivir 75mg Twice Daily - 75mg oral oseltamivir twice daily plus intravenous placebo zanamivir twice daily
Treatment: Drugs: Zanamivir
Zanamivir aqueous solution, 10 mg/mL, will be provided as a single use, sterile clear, colorless preparation in 20 mL clear glass vials.
Treatment: Drugs: Placebo to match zanamivir
Placebo to match IV zanamivir will be provided as a normal saline solution of a matched volume.
Treatment: Drugs: Oseltamivir
Oseltamivir will be provided as over-encapsulated 75 mg capsules.
Treatment: Drugs: Placebo to match oseltamivir
Placebo to match oral oseltamivir will be provided as capsules with a common excipient of appropriate quality.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Time to Clinical Response (TTCR) in Participants With Confirmed Influenza
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Assessment method [1]
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Clinical response is defined as the resolution of at least 4 of the 5 vital signs (temperature, oxygen saturation, respiratory status, heart rate, systolic blood pressure) within the respective resolution criteria, maintained for at least 24 hours, or hospital discharge, whichever occurred first. This analysis was performed for Influenza positive population, for those with symptom onset less than or equal to (\<=) 4 days, and for those on mechanical (mech) ventilation or in intensive care unit (ICU). 99 days is censored time for the participants who did not achieve TTCR.
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Timepoint [1]
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Up to 42 days
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Secondary outcome [1]
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Percentage of Participants With Respiratory Improvement
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Assessment method [1]
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Respiratory Status (RS) is a component of TTCR. Response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), a need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate of =\<24 breaths/minute (without supplemental oxygen). Data are presented as the percentage of participants achieving respiratory improvement.
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Timepoint [1]
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Up to 42 days
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Secondary outcome [2]
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Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit
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Assessment method [2]
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The number of participants who died on or before Day 14, Day 28, and the End of Study Visit were summarized.
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Timepoint [2]
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On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days)
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Secondary outcome [3]
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Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score
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Assessment method [3]
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The Katz ADL scores were collected for bathing, dressing, toileting, transferring, continence, and feeding activities and were assessed once daily during the treatment period/hospitalization and once at each post-treatment Clinic Visit. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline is defined as the difference at each time point (Day 5/6, and Day 10/11, and last day S/R if treatment was extended beyond 5 days) and the end of the study (post-treatment \[PT\] +28 Days) compared to Baseline.
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Timepoint [3]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [4]
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Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score
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Assessment method [4]
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Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. Median time to return to pre-morbid functional status was assessed via the Katz ADL score (bathing, dressing, toileting, transferring, continence, and feeding activities). For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent.
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Timepoint [4]
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Up to 42 days
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Secondary outcome [5]
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Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study
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Assessment method [5]
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Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. The number of participants who returned to their pre-morbid functional status at the end of the study assessed per the Katz ADL score (bathing, dressing, toileting, transferring, continence and feeding activities) is summarized.
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Timepoint [5]
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Up to 42 days
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Secondary outcome [6]
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Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale
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Assessment method [6]
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Median time to return to pre-morbid level of activity was assessed once daily during treatment/hospitalization and once at each post-treatment assessment and was measured using the 3- point scale (bed rest, limited ambulation, or unrestricted).
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Timepoint [6]
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Up to 42 days
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Secondary outcome [7]
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Number of Participants With the Indicated Clinical Symptoms of Influenza
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Assessment method [7]
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Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient hospitalization and once at each post-treatment assessment.
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Timepoint [7]
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Up to 42 days
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Secondary outcome [8]
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Median Time of Duration of Clinical Symptoms of Influenza
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Assessment method [8]
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Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient/hospitalization and once at each post-treatment assessment.
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Timepoint [8]
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Up to 42 days
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Secondary outcome [9]
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Number of Participants With Complications of Influenza and Associated Antibiotic Use
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Assessment method [9]
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The number of participants with complications of influenza and associated antibiotic use were summarized
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Timepoint [9]
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Up to 42 days
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Secondary outcome [10]
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Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
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Assessment method [10]
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Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD), no supplemental oxygen (O2) or ventilation support, Respiratory support at "any time (AT) on study" and at Baseline (Day 1) are summarized. Data for the "any time (AT) on study" time point was reported.
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Timepoint [10]
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Up to 42 days
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Secondary outcome [11]
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Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
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Assessment method [11]
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Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitalization and once at each post-treatment clinic visit.
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Timepoint [11]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [12]
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Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay
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Assessment method [12]
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Hospital duration and ICU duration was assessed from the first day of dosing. Hospital duration was calculated as the discharge date minus the admission date + 1. Hospital duration while on study was the earlier of discharge, completion, or withdrawal minus the later of the admission date or the study start date + 1. ICU duration-Modified was calculated as the original ICU duration minus ICU days prior to Study Day 1.
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Timepoint [12]
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Day 1 to the end of the study (assessed up to 42 days)
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Secondary outcome [13]
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Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure
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Assessment method [13]
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The absence of fever is defined as a non-axillary temperature recording \<=36.6 degrees Celsius axillary, \<= 37.2 degrees Celsius oral or \<= 37.7 degrees Celsius core. Respiratory Status (RS) response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), or the need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate =\<24 breaths/minute (without supplemental oxygen). Oxygen saturation response criteria: \>=95% (without supplemental oxygen). Heart rate response criteria: =\<100 beats/minute. Systolic blood pressure response criteria: \>=90 millimeters of mercury. Vital signs were assessed three times daily during the treatment period/hospitalization. Vital signs were assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit.
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Timepoint [13]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [14]
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Median Time to Virologic Improvement
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Assessment method [14]
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Virologic improvement is defined as a 2 log drop in viral load or sustained undetectable viral ribonucleic acid (RNA) (on two successive occasions) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples. Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Days 6, 8, 10 and on the last day of randomized treatment. For participants who utilized the Switch (S)/Rescue (R) option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Nasopharyngeal swabs were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16, and +28 day assessment.
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Timepoint [14]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [15]
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Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline
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Assessment method [15]
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Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day1, S/R Day3, S/R Day5, or S/R Day6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16 and +28Day assessment. Viral load was measured by Quantitative Virus Culture, log10 50% Tissue Culture Infectious Dose (TCID50)/milliliter (mL). Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus Baseline value .
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Timepoint [15]
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Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
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Secondary outcome [16]
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Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline
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Assessment method [16]
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Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the post-treatment +2, +5, +9, +16 and +28 day assessment. Viral load as measured by PCR. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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Timepoint [16]
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Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
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Secondary outcome [17]
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Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate)
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Assessment method [17]
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Lower respiratory samples included BAL and endotracheal aspirates. Endotracheal aspirates were requested in participants (par.) who were intubated. Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment \[trt\]). Endotracheal aspirates were collected in participants who were intubated. If trt was continued beyond Day 5, additional samples were taken on Trt Day 6, Day 8, Day 10, and/or the day of the last dose of randomized trt, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R trt. If the par. was symptomatic and hospitalized, samples were taken on the Post-Trt +2, +5, +9, +16 assessment days, and at the Post-Trt \[PT\]+28 Day assessment. Assessment of samples was done by quantitative RT-PCR and viral culture.
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Timepoint [17]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [18]
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Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples)
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Assessment method [18]
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Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples, where available) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment). Endotracheal aspirates were collected in participants who were intubated. If treatment was continued beyond Day 5, additional samples were taken on Treatment Day 6, Day 8, Day 10, and/or the day of the last dose of randomized treatment, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R treatment. If the participant was symptomatic and hospitalized, samples were taken on the Post-treatment+2, +5, +9, +16 assessment days, and at the Post-Treatment +28 Day. Assessment of samples was done by quantitative RT-PCR.
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Timepoint [18]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [19]
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Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples
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Assessment method [19]
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Nasopharyngeal swabs and endotracheal /BAL samples were collected for viral susceptibility analysis. Susceptibility analyses consisted of phenotyping and genotyping. Resistance mutations were detected by genotyping. Viral susceptibility to zanamivir and oral oseltamivir at Baseline and throughout treatment determined by NA and HA (gene of influenza A and B viruses) sequence analysis and NA enzyme inhibition. Number of participants with viral mutation events are summarized, this includes all resistance mutations (substitutions) i.e. those present at Baseline and those that emerged during treatment.
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Timepoint [19]
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Baseline (Day 1) and up to 42 days
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Secondary outcome [20]
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Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
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Assessment method [20]
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An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. All AEs were assessed by the Investigator as related or not related to the study treatment.
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Timepoint [20]
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Up to 42 days
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Secondary outcome [21]
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Number of Participants With Any Severe or Grade 3/4 AE
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Assessment method [21]
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An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of AEs. Grade 3=severe; Grade 4=potentially life threatening.
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Timepoint [21]
0
0
Up to 42 days
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Secondary outcome [22]
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Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
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Assessment method [22]
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An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
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Timepoint [22]
0
0
Up to 42 days
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Secondary outcome [23]
0
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Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
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Assessment method [23]
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0
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
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Timepoint [23]
0
0
Up to 42 days
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Secondary outcome [24]
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Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
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Assessment method [24]
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0
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assessed by the Investigator as related or not related to the study treatment.
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Timepoint [24]
0
0
Up to 42 days
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Secondary outcome [25]
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Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days
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Assessment method [25]
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Samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), switch/rescue (S/R) Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino tranferase (AST), total bilirubin, calcium, creatine kinase, chloride, carbon dioxide content (CO2), creatinine, potassium, magnesium, sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range are summarized.
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Timepoint [25]
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0
Baseline (Day 1) and up to 42 days
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Secondary outcome [26]
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Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days
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Assessment method [26]
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Blood samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), S/R Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC) count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range for the indicated hematology parameters is summarized. Baseline is defined as the pre-dose value collected on Study Day 1.
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Timepoint [26]
0
0
Baseline (Day 1) and up to 42 days
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Secondary outcome [27]
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Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities
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Assessment method [27]
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A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatine kinase, chloride, CO2/bicarbonate, creatinine, potassium, magnesium and sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
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Timepoint [27]
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0
Baseline (Day 1) and up to 42 days
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Secondary outcome [28]
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0
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
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Assessment method [28]
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A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
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Timepoint [28]
0
0
Baseline (Day 1) and up to 42 days
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Secondary outcome [29]
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0
Median Quantity of Oxygen Delivery Measured at Baseline (Day 1) and During the Study
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Assessment method [29]
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Oxygen delivery were assessed three times daily at Baseline (Day 1) and during the treatment period/hospitalization (ideally at least 6 hours apart) and once daily during inpatient/hospitalization and once at Post +5 days, +16 days, and +28 days clinic visits. The median quantity of oxygen delivery during the study was not summarized since the data was not collected in a way to accurately calculate values. Baseline is defined as the pre-dose value collected on Study Day 1.
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Timepoint [29]
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0
Baseline (Day 1) and during the study
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Secondary outcome [30]
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0
Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4
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Assessment method [30]
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On Baseline/Day 1, a 12-lead ECG was obtained within approximately 24 hours prior to dosing. The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. In the original protocol ECGs were also done on Day 4, however, amendment 2 removed this requirement and therefore not all participants had Day 4 ECGs.
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Timepoint [30]
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0
Baseline (Day 1) and Day 4
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Secondary outcome [31]
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0
Serum Concentration of IV Zanamivir
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Assessment method [31]
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Pharmacokinetic samples were collected at four time points to characterize peak concentration (end of infusion; C\[EOI\]) after the first dose on Day 1 and on Day 4 to characterize the pre-dose concentration (C\[0\]), the peak concentration C(EOI), and the trough concentration at 11-12 hours post-dose (C\[12\]) of zanamavir. Data was summarized by Creatinine clearance (CL) Category. The dose on Day 1 is the initial dose (unadjusted) and the dose on Day 4 is the maintenance dose.
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Timepoint [31]
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0
Day 1 and Day 4
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Eligibility
Key inclusion criteria
* Male or female aged 16 years; a female is eligible to enter and participate in the study if she is:
1. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or,
2. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to use protocol specified methods of birth control while on study.
* Vital signs criteria defined as 3 or more of the following at Baseline:
1. Presence of fever [oral temperature of 38°C or equivalent] at Baseline. However, this requirement is waived if the subject has a history of fever within in the 24 hours prior to Baseline; or, if the subject reported symptoms of feverishness at some time during the 48 hours prior to Baseline.
AND at least 2 out of the following 4:
2. Oxygen saturation <95% on room air by trans-cutaneous method or need for any supplemental oxygenation or ventilatory support, or increase in oxygen supplementation requirement of =2 litres for subjects with chronic oxygen dependency. For those subjects with a history of chronic hypoxia (without supplemental oxygen), an oxygen saturation of at least 3% below the patient's historical baseline oxygen saturation will satisfy this criterion.
3. Respiration rate >24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived.
4. Heart rate >100 beats per minute.
5. Systolic blood pressure <90 mmHg.
* Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting.
* Clinical symptoms of influenza with positive influenza diagnostic test result or strong suspicion of influenza illness based on clinical symptoms and local surveillance information.
* Subjects willing and able to give written informed consent to participate in the study and to adhere to the procedures stated in the protocol, or legally acceptable representative willing and able to give written informed consent on behalf of the subject for minors, unconscious adults and those incapable of consenting themselves due to their medical condition, or included as permitted by local regulatory authorities, IRB/IECs or local laws.
* Severity of any medical illness that, in the Investigator's judgement, justifies hospitalization of the subject for treatment and supportive care
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Query!
Minimum age
16
Years
Query!
Query!
Maximum age
No limit
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Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy in the period from onset of symptoms and prior to enrolment.
* Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline.
* Subjects who are considered to require concurrent therapy with another influenza antiviral medication.
* Subjects who are known or suspected to be hypersensitive to any component of the study medications.
* Subjects with creatinine clearance =10 mL/min who are not being treated with continuous renal replacement therapy (CRRT).
* Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline
* Subjects who require routine/intermittent hemodialysis or continuous peritoneal dialysis (due to inability to provide appropriate dosing schedule for oseltamivir) at Baseline. CRRT modalities are allowed.
* Liver toxicity criteria based on local laboratory results obtained within 24 hours of Baseline:
1. ALT or AST 3xULN and bilirubin 2xULN
2. ALT 5xULN
* Underlying chronic liver disease with evidence of severe liver impairment.
* History of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject.
* Females who are pregnant or are breastfeeding.
* Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline.
* French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Query!
Query!
Query!
Intervention assignment
Parallel
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Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
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Date of first participant enrolment
Anticipated
Query!
Actual
15/01/2011
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Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
18/03/2015
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
626
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Query!
Recruitment hospital [1]
0
0
GSK Investigational Site - Westmead
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Recruitment hospital [2]
0
0
GSK Investigational Site - Herston
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Recruitment hospital [3]
0
0
GSK Investigational Site - Adelaide
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Recruitment hospital [4]
0
0
GSK Investigational Site - Bedford Park
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Recruitment hospital [5]
0
0
GSK Investigational Site - Clayton
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Recruitment hospital [6]
0
0
GSK Investigational Site - Heidelberg
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Recruitment hospital [7]
0
0
GSK Investigational Site - Melbourne
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Recruitment hospital [8]
0
0
GSK Investigational Site - Perth
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Recruitment postcode(s) [1]
0
0
2145 - Westmead
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Recruitment postcode(s) [2]
0
0
4029 - Herston
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Recruitment postcode(s) [3]
0
0
5000 - Adelaide
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Recruitment postcode(s) [4]
0
0
5043 - Bedford Park
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Recruitment postcode(s) [5]
0
0
3168 - Clayton
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Recruitment postcode(s) [6]
0
0
3084 - Heidelberg
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Recruitment postcode(s) [7]
0
0
3004 - Melbourne
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Recruitment postcode(s) [8]
0
0
3050 - Melbourne
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Recruitment postcode(s) [9]
0
0
6000 - Perth
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Recruitment outside Australia
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0
0
United States of America
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0
0
Alabama
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0
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Arizona
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United States of America
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California
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Colorado
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Connecticut
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Florida
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Idaho
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United States of America
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Illinois
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Iowa
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Kansas
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Kentucky
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Massachusetts
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Michigan
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Missouri
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Nevada
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Wisconsin
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Belgium
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Brussel
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Belgium
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Bruxelles
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Belgium
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Leuven
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Belgium
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Liege
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Brazil
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Rio de Janeiro
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Brazil
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São Paulo
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Alberta
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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China
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Hainan
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China
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Hunan
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China
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Jiangxi
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China
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Jilin
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China
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Shaanxi
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China
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Zhejiang
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China
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Beijing
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China
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Chengdu
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China
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Chongqing
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China
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Guangzhou
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China
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Hangzhou
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China
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Shanghai
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China
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Tianjin
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Colombia
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Bogotá
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Czechia
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0
Brno - Bohunice
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Czechia
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Brno
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0
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Czechia
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Hradec Kralove
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0
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Czechia
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Praha 8
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0
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Denmark
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Aarhus N
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0
0
Denmark
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Hvidovre
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0
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Denmark
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Odense C
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France
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Dijon Cedex
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France
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Limoges cedex
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France
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Nîmes cedex 9
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0
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France
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0
Orléans cedex 2
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0
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France
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0
Poitiers Cedex
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0
0
France
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0
0
Tours cedex 9
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0
0
Germany
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0
Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Saarland
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Greece
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Chaidari
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Greece
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Goudi, Athens
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Hong Kong
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Kwun Tong
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Hong Kong
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Shatin
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Hong Kong
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Tuen Mun
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Hungary
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Debrecen
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Hungary
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Kaposvár
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Hungary
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Miskolc
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Hungary
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Szombathely
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Hungary
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Székesfehérvár
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India
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Bangalore
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India
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Civil Lines
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India
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Lucknow
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India
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Pune
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India
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Trivandrum
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Korea, Republic of
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Guro Gu
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Gyeonggi
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Kangwon-do
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Seoul
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Mexico
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Estado De México
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Mexico
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Jalisco
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Mexico
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Nuevo León
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Mexico
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Aguascalientes
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Mexico
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Chihuahua
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Netherlands
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Nijmegen
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Auckland
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Christchurch
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Hamilton
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New Zealand
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Hastings
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New Zealand
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Newtown
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Norway
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Bergen
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Norway
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Trondheim
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Poland
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Chorzow
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Poland
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Debica
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Trzebnica
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Poland
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Warszawa
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Russian Federation
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Barnaul
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Smolensk
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Slovakia
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Bratislava
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Slovakia
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Martin
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South Africa
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Mpumalanga
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South Africa
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Bellville
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South Africa
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Die Wilgers
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South Africa
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Les Marais
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South Africa
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Panorama
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South Africa
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Worcester
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Spain
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Alicante
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Spain
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Badalona
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Spain
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Barcelona
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Granada
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Spain
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L'Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Murcia
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Oviedo
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Spain
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Pama de Mallorca
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Taipei
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Thailand
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Bangkok
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United Kingdom
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Bristol
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United Kingdom
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Cardiff
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United Kingdom
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Liverpool
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United Kingdom
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to test the safety and efficacy of zanamivir given intravenously and how well it works at two different doses in hospitalized adolescents and adults with flu. Zanamivir will be compared with oseltamivir, which is used for treating flu.
Query!
Trial website
https://clinicaltrials.gov/study/NCT01231620
Query!
Trial related presentations / publications
Marty FM, Vidal-Puigserver J, Clark C, Gupta SK, Merino E, Garot D, Chapman MJ, Jacobs F, Rodriguez-Noriega E, Husa P, Shortino D, Watson HA, Yates PJ, Peppercorn AF. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med. 2017 Feb;5(2):135-146. doi: 10.1016/S2213-2600(16)30435-0. Epub 2017 Jan 14.
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Public notes
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Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
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Address
0
0
GlaxoSmithKline
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
Query!
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01231620