Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01227967
Registration number
NCT01227967
Ethics application status
Date submitted
22/10/2010
Date registered
25/10/2010
Date last updated
4/02/2019
Titles & IDs
Public title
Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
Query!
Scientific title
A Randomized Double-Blind Phase 2 Study Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications
Query!
Secondary ID [1]
0
0
10-I-0210
Query!
Secondary ID [2]
0
0
10-I-0210
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
IRC003
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Influenza
0
0
Query!
Condition category
Condition code
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Amantadine, Ribavirin, Oseltamivir
Treatment: Drugs - Oseltamivir
Experimental: Combination Therapy - Amantadine, Ribavirin, Oseltamivir
Active Comparator: Oseltamivir monotherapy - Oseltamivir
Treatment: Drugs: Amantadine, Ribavirin, Oseltamivir
Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.
Treatment: Drugs: Oseltamivir
Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs
Query!
Assessment method [1]
0
0
The central laboratory performed a qualitative PCR test on the NP sample from Day 0 in order to confirm influenza infection and to determine the influenza type and subtype. For participants with a positive influenza test result at Day 0 from this qualitative PCR testing, the laboratory then performed qPCR testing of subsequent samples to quantify viral shedding.
Query!
Timepoint [1]
0
0
At Day 3
Query!
Secondary outcome [1]
0
0
Number of Participants by Virus Detection Status
Query!
Assessment method [1]
0
0
Number of participants who had undetectable values (less than the limit of detection [LOD]), who had values between the LOD and the lower limit of quantification (LLOQ), and who had values =LLOQ
Query!
Timepoint [1]
0
0
At Day 0, 3 and 7.
Query!
Secondary outcome [2]
0
0
qPCR Viral Shedding
Query!
Assessment method [2]
0
0
Median, 25% and 75% percentile of the value of viral shedding (Results <LOD were imputed as the LOD value, and Results >= LOD, <LLOQ were imputed as the LLOQ value.)
Query!
Timepoint [2]
0
0
At Day 0, 3 and 7
Query!
Secondary outcome [3]
0
0
Number of Participants Shedding Virus
Query!
Assessment method [3]
0
0
Number of participants with undetectable viral load at both Day 3 and Day 7; detectable at Day 3 and undetectable at Day 7; detectable at Day 7 (irrespective of whether or not detectable at Day 3).
Query!
Timepoint [3]
0
0
At day 3 and 7.
Query!
Secondary outcome [4]
0
0
Time to Alleviation of Influenza Clinical Symptoms.
Query!
Assessment method [4]
0
0
The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Duration of clinical symptoms is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1 (mild). A measurement is considered to be the 8AM or 8PM assessment during Days 0 to 7 (so two measurements are obtained per day) and then the daily assessment thereafter. Time will then be calculated in half-days through to Day 7. If a subject's first two assessments on (baseline assessment and first subsequent diary card assessment) satisfy this criterion, then the duration will be set to zero. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms evaluated.
Query!
Timepoint [4]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [5]
0
0
Time to Absence of Fever
Query!
Assessment method [5]
0
0
Fever was considered present based on the diary cards if a subject reported a maximal temperature =38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Otherwise, fever was considered not present during the period since the diary card was previously completed, except that the evaluation was considered missing if either the temperature or the antipyretic drug use entry was not completed on the diary card. The duration of fever was defined as the time from Day 0 to the first of two successive assessments (through to Day 7) or to the first assessment (Day 8 onwards) at which no fever was present according to this definition.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with fever evaluated.
Query!
Timepoint [5]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [6]
0
0
Time to Resolution of All Symptoms AND Fever
Query!
Assessment method [6]
0
0
The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Fever was considered present based on the diary cards if a subject reported a maximal temperature =38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Time to resolution of all clinical symptoms and fever is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1(mild) and no fever >=38.0 C or antipyretic drug is reported. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms and fever evaluated.
Query!
Timepoint [6]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [7]
0
0
Time to Feeling as Good as Before the Onset of the Influenza Illness
Query!
Assessment method [7]
0
0
Time to feeling as good as before influenza is defined as time to the first of two successive 'yes' responses to the question of 'feeling as good as you did before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered.
Query!
Timepoint [7]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [8]
0
0
Time to Return to Pre-influenza Function
Query!
Assessment method [8]
0
0
Time to return to pre-influenza function is defined as the time from Day 0 to the first of two successive 'Yes' answers to the global assessment question 'Are you functioning as well as you were before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered.
Query!
Timepoint [8]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [9]
0
0
Time to Return of Physical Function to Pre-illness Leve
Query!
Assessment method [9]
0
0
Time to return of physical function to pre-illness level was defined as the time from Day 0 to the first of two successive measurements at which the physical function score equals or is better than the pre-illness score (obtained by recall at enrollment).For subjects who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with physical function evaluated.
Query!
Timepoint [9]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [10]
0
0
Percentage of Participants With Clinical Failure at Day 5
Query!
Assessment method [10]
0
0
Clinical failure at Day 5 is defined as the need for continued (non-study) antiviral use after Day 5.
Query!
Timepoint [10]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [11]
0
0
Percentage of Participants Who Develop Bronchitis, Pneumonia, or Other Complications of Influenza After Day 0.
Query!
Assessment method [11]
0
0
Participants were assessed for the signs/symptoms suggestive of one of the following complications: Sinusitis, Otitis Media ,Bronchitis / Bronchiolitis, Pneumonia and antibiotic use for reason other than above.
Query!
Timepoint [11]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [12]
0
0
Percentage of Participants Who Required New or Increased Use of Supplemental Oxygen
Query!
Assessment method [12]
0
0
Percentage of participants who required new or increased use of supplemental oxygen
Query!
Timepoint [12]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [13]
0
0
Percentage of Participants Who Required Hospitalization.
Query!
Assessment method [13]
0
0
The percentage of participants hospitalized by 28 days was estimated from the Kaplan-Meier curves.
Query!
Timepoint [13]
0
0
From treatment initiation to Day 28
Query!
Secondary outcome [14]
0
0
28-day Mortality
Query!
Assessment method [14]
0
0
Number of deaths
Query!
Timepoint [14]
0
0
From treatment initiation to Day 28
Query!
Eligibility
Key inclusion criteria
- INCLUSION CRITERIA:
Enrollment (Screening)
1. Signed informed consent prior to initiation of any study procedures
2. Presence of an underlying medical condition(s) that might increase risk of
complications from influenza
3. History of an influenza-like illness defined as:
- One or more respiratory symptom (cough, sore throat, or nasal symptoms) AND
- Either
- Fever (subjective or documented >38 degrees C) OR
- 1 or more constitutional symptom (headache, malaise, myalgia, sweats/chills or
fatigue)
4. Onset of illness no more than 96 hours before screening defined as when the subject
experienced at least one respiratory symptom, constitutional symptom, or fever
5. Willingness to have samples stored
Randomization
1. Signed informed consent
2. Presence of a medical condition(s) that had been associated with increased risk of
complications from influenza
- Age 65 years of age or older
- Asthma
- Neurological and neuro-developmental conditions (including disorders of the
brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy
[seizure disorders], stroke, moderate to severe developmental delay, muscular
dystrophy, or spinal cord injury) [though still able to provide informed consent
per inclusion criteria #1]
- Chronic lung disease (such as COPD and cystic fibrosis)
- Heart disease (such as congenital heart disease, congestive heart failure, and
coronary artery disease)
- Blood disorders (excluding genetic causes of anemia, as noted in the exclusion
criteria)
- Endocrine disorders (such as diabetes mellitus)
- Kidney disorders
- Liver disorders
- Metabolic disorders (such as inherited metabolic disorders and mitochondrial
disorders)
- Weakened immune system due to disease or medication (such as people with
HIV/AIDS, or cancer, chronic steroids or other medications causing immune
suppression)
- BMI = 40(kg/m²)
3. Onset of illness no more than 96 hours before screening defined as when the subject
experienced at least one respiratory symptom, constitutional symptom, or fever
4. Positive test for influenza (either rapid antigen or PCR)
- Results from influenza testing obtained for clinical indications within 12 hours
before screening/enrollment may be used if available. Randomization may proceed in
cases of discrepant results (one positive and one negative)
5. One of the following to avoid pregnancy:
- Females who were able to become pregnant (i.e., are not postmenopausal, have not
undergone surgical sterilization, and are sexually active with men) must agree to
use at least 2 effective forms of contraception from the date of informed consent
through 6 months after the last dose of study drug. At least one of the methods
of contraception should be a barrier method
- Males who had not undergone surgical sterilization and are sexually active with
women must agree to use condoms plus have a partner use at least one additional
effective form of contraception from the date of informed consent through 6
months after the last dose of study drug
6. Willingness to have samples stored
EXCLUSION CRITERIA:
(for Enrollment or Randomization)
1. Women who were pregnant or breast-feeding, and men whose female partner(s) was
pregnant
2. Inability to take oral medication or a history of gastrointestinal malabsorption that
would preclude the use of oral medication.
3. Hemoglobin < 10 g/dL
4. WBC < 1.5 times 10(9)/L
5. Neutrophils < 0.75 x 10(9)/L
6. Platelets < 50 x 10(9)/L
7. History of genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or
autoimmune hemolytic anemia
8. Received more than 2 doses of any antiviral influenza medications since onset of
influenza symptoms
9. Received stavudine (d4T), didanosine (ddI), zidovudine (AZT), or azathioprine within
30 days prior to study entry
10. Creatinine clearance less than 60 mL/min (estimated by the Cockcroft-Gault equation
using serum creatinine)
11. History of autoimmune hepatitis
12. Uncompensated liver disease (defined as AST > 3 times site upper limit of normal
(ULN), ALT > 3 times ULN, or Direct Bilirubin > 2 times ULN)
13. Clinical signs of end-stage liver disease including jaundice, coagulopathy, portal
hypertension, esophageal varices, ascites, peripheral edema, gastrointestinal
bleeding, or encephalopathy
14. Chronic liver disease categorized as Child-Pugh class C (Child-Pugh score 10-15)
15. Known hypersensitivity to rimantadine, amantadine, ribavirin, oseltamivir, peramivir,
or zanamivir
16. Received live attenuated virus vaccine (influenza or other) within 3 weeks prior to
study entry
17. Use of any investigational drug within 30 days or 5 half-lives (whichever was longer)
prior to study entry
18. Participation in other research protocols that would require more than 100 mL of blood
to be drawn in any 4-week period that overlaps with this study.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
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 analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
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
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/09/2010
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
30/03/2017
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
881
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Query!
Recruitment hospital [1]
0
0
Holdsworth House Med Practice - Darlinghurst
Query!
Recruitment hospital [2]
0
0
Taylor Square Private Clinic - Darlinghurst
Query!
Recruitment hospital [3]
0
0
Westmead Hospital - Westmead
Query!
Recruitment hospital [4]
0
0
Royal Brisbane - Herston
Query!
Recruitment hospital [5]
0
0
Northside Clinic - Fitzroy North
Query!
Recruitment hospital [6]
0
0
The Alfred Hospital - Melbourne
Query!
Recruitment hospital [7]
0
0
Royal Melbourne Hospital - Parkville
Query!
Recruitment postcode(s) [1]
0
0
2010 - Darlinghurst
Query!
Recruitment postcode(s) [2]
0
0
- Westmead
Query!
Recruitment postcode(s) [3]
0
0
4029 - Herston
Query!
Recruitment postcode(s) [4]
0
0
3068 - Fitzroy North
Query!
Recruitment postcode(s) [5]
0
0
3004 - Melbourne
Query!
Recruitment postcode(s) [6]
0
0
3052 - Parkville
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Arizona
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
California
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Colorado
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Illinois
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Iowa
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Kentucky
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Louisiana
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Maryland
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Massachusetts
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Michigan
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Missouri
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Nebraska
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
New Jersey
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
New York
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
North Carolina
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Ohio
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Pennsylvania
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
South Dakota
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Tennessee
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Texas
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Virginia
Query!
Country [24]
0
0
Argentina
Query!
State/province [24]
0
0
Buenos Aires
Query!
Country [25]
0
0
Argentina
Query!
State/province [25]
0
0
Provincia De Buenos Aires
Query!
Country [26]
0
0
Argentina
Query!
State/province [26]
0
0
Cordoba
Query!
Country [27]
0
0
Argentina
Query!
State/province [27]
0
0
Santa Fe
Query!
Country [28]
0
0
Mexico
Query!
State/province [28]
0
0
México City
Query!
Country [29]
0
0
Mexico
Query!
State/province [29]
0
0
Tlalpan
Query!
Country [30]
0
0
Thailand
Query!
State/province [30]
0
0
Bangkok
Query!
Country [31]
0
0
Thailand
Query!
State/province [31]
0
0
Khon Kaen
Query!
Country [32]
0
0
Thailand
Query!
State/province [32]
0
0
Nonthaburi
Query!
Funding & Sponsors
Primary sponsor type
Government body
Query!
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
Seasonal influenza is responsible for many hospitalizations and deaths each year, despite
effective antiviral treatments. Some individuals have medical conditions such as heart or
lung diseases that make them particularly at risk of severe influenza infections that may
result in hospitalization or death. Oseltamivir (Tamiflu) is used most often to treat flu,
but there are still many hospitalizations, complications, and deaths even with treatment.
This study evaluated the use of combination antivirals (amantadine, oseltamivir, and
ribavirin) compared to oseltamivir alone in the treatment of influenza in an at-risk
population.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01227967
Query!
Trial related presentations / publications
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
Monto AS. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006 Jan;12(1):55-60. doi: 10.3201/eid1201.051068.
Moscona A. Oseltamivir resistance--disabling our influenza defenses. N Engl J Med. 2005 Dec 22;353(25):2633-6. doi: 10.1056/NEJMp058291. No abstract available.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
John Beigel, MD
Query!
Address
0
0
Leidos Biomedical Research, Inc. in support of Clinical Research Section, LIR, NIAID, Natinal Institutes of Health
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01227967
Download to PDF