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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02851407
Registration number
NCT02851407
Ethics application status
Date submitted
27/07/2016
Date registered
1/08/2016
Date last updated
2/03/2022
Titles & IDs
Public title
Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients
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Scientific title
A Phase 3, Randomized, Adaptive Study Comparing the Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant
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Secondary ID [1]
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15-007
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Veno-occlusive Disease
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Condition category
Condition code
Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Oral and Gastrointestinal
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0
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Defibrotide
Other interventions - Best Supportive Care
Experimental: Defibrotide - Defibrotide is administered intravenously at a dose of 25 mg/kg/day in addition to best supportive care on the day before the first day of the conditioning regimen and will continue (for those patients without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post HSCT
Other: Best Supportive Care - Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and patient need, is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner, or diagnosis of VOD, if applicable
Treatment: Drugs: Defibrotide
Other interventions: Best Supportive Care
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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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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Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
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Assessment method [1]
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VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +30 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +30 post-HSCT.
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Timepoint [1]
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Day +30 Post-HSCT
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Secondary outcome [1]
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Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
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Assessment method [1]
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VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +100 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +100 post-HSCT.
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Timepoint [1]
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Day +100 Post-HSCT
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Secondary outcome [2]
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Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)
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Assessment method [2]
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The number of participants who were diagnosed with VOD based on the Modified Seattle Criteria as per blinded EPAC assessment. The percentage was calculated out of the total number of participants in each arm of the study. The values reported below are the numbers and percentages of participants who experienced VOD by Day +30 post-HSCT.
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Timepoint [2]
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Day +30 Post-HSCT
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Secondary outcome [3]
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Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
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Assessment method [3]
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VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria. An event is defined as a VOD diagnosis or death, whichever, is earlier, up to and including Day +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was based on Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments. The values reported below are participants who did not experience VOD or death by Day +180 post-HSCT.
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Timepoint [3]
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Day +180 Post-HSCT
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Secondary outcome [4]
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Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
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Assessment method [4]
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NRM is defined as death that occurs after HSCT in participants who were noted as having malignant primary disease on the disease history electronic case report form (eCRF) and do not have primary disease relapse post-HSCT.
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Timepoint [4]
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Days +100 and +180 Post-HSCT
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Secondary outcome [5]
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Percentage of Participants With Veno-Occlusive Disease (VOD)-Associated Multi-Organ Dysfunction (MOD) by Days +30 and Days +100 Post-Hematopoietic Stem Cell Transplant (HSCT) in Patients Who Developed VOD
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Assessment method [5]
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VOD-associated MOD is defined for participants as occurring if the investigator answers "Yes" to the question "Has the participant been diagnosed with VOD associated MOD?" in the electronic case report form (eCRF). The values below are the number of participants who received the answer, "Yes."
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Timepoint [5]
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Days +30 and +100 Post-HSCT
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Secondary outcome [6]
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Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
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Assessment method [6]
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The proportion of participants who had resolution of VOD by Day +180 post-HSCT is reported as a percentage.
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Timepoint [6]
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Day +180 Post-HSCT
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Secondary outcome [7]
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Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
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Assessment method [7]
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Time to Resolution of VOD is calculated as follows: Time to Resolution of VOD= [Date of VOD resolution] - [Date of VOD diagnosis by investigator].
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Timepoint [7]
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Day +180 Post-HSCT
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Secondary outcome [8]
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Percentage of Participants With Veno-Occlusive Disease (VOD) After Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) up to Days +100 and +180 Post-HSCT
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Assessment method [8]
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The values shown are the number and percentage of participants with VOD after day +30 post-HSCT and on or before Days +100 and +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was made by Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments.
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Timepoint [8]
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Days +100 and +180 Post-HSCT
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Secondary outcome [9]
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Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age = 16 Years: Mobility
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Assessment method [9]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [9]
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Day +180 Post-HSCT
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Secondary outcome [10]
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Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age = 16 Years: Self-Care
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Assessment method [10]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [10]
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Day +180 Post-HSCT
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Secondary outcome [11]
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Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age = 16 Years: Activity
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Assessment method [11]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [11]
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Day +180 Post-HSCT
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Secondary outcome [12]
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Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age = 16 Years: Pain
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Assessment method [12]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [12]
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Day +180 Post-HSCT
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Secondary outcome [13]
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Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age = 16 Years: Anxiety
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Assessment method [13]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [13]
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0
Day +180 Post-HSCT
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Secondary outcome [14]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 4 and = 7 Years: Mobility
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Assessment method [14]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [14]
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0
Day +180 Post-HSCT
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Secondary outcome [15]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 4 and = 7 Years: Self-Care
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Assessment method [15]
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For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [15]
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0
Day +180 Post-HSCT
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Secondary outcome [16]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 4 and = 7 Years: Activity
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Assessment method [16]
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0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [16]
0
0
Day +180 Post-HSCT
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Secondary outcome [17]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 4 and = 7 Years: Pain
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Assessment method [17]
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0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [17]
0
0
Day +180 Post-HSCT
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Secondary outcome [18]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 4 and = 7 Years: Anxiety
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Assessment method [18]
0
0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [18]
0
0
Day +180 Post-HSCT
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Secondary outcome [19]
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Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 8 and = 15 Years: Mobility
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Assessment method [19]
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0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [19]
0
0
Day +180 Post-HSCT
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Secondary outcome [20]
0
0
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 8 and = 15 Years: Self-Care
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Assessment method [20]
0
0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [20]
0
0
Day +180 Post-HSCT
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Secondary outcome [21]
0
0
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 8 and = 15 Years: Activity
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Assessment method [21]
0
0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [21]
0
0
Day +180 Post-HSCT
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Secondary outcome [22]
0
0
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 8 and = 15 Years: Pain
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Assessment method [22]
0
0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [22]
0
0
Day +180 Post-HSCT
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Secondary outcome [23]
0
0
Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age = 8 and = 15 Years: Anxiety
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Assessment method [23]
0
0
For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
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Timepoint [23]
0
0
Day +180 Post-HSCT
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Secondary outcome [24]
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0
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase
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Assessment method [24]
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0
Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
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Timepoint [24]
0
0
Day +1 and +7 Post-HSCT
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Secondary outcome [25]
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0
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase
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Assessment method [25]
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0
AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Query!
Timepoint [25]
0
0
Day +1 and +7 Post-HSCT
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Secondary outcome [26]
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0
Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase
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Assessment method [26]
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0
Mean systemic clearance after intravenous dosing. Mean clearance is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Query!
Timepoint [26]
0
0
Day +1 and +7 Post-HSCT
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Secondary outcome [27]
0
0
Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase
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Assessment method [27]
0
0
Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis.If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Query!
Timepoint [27]
0
0
Day +1 and +7 Post-HSCT
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Secondary outcome [28]
0
0
Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase
Query!
Assessment method [28]
0
0
Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Query!
Timepoint [28]
0
0
Day +14 Post-VOD Treatment
Query!
Secondary outcome [29]
0
0
Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase
Query!
Assessment method [29]
0
0
AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Query!
Timepoint [29]
0
0
Day +14 Post-VOD Treatment
Query!
Secondary outcome [30]
0
0
Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase
Query!
Assessment method [30]
0
0
Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Query!
Timepoint [30]
0
0
Day +14 Post-VOD Treatment
Query!
Secondary outcome [31]
0
0
Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Prophylaxis Phase
Query!
Assessment method [31]
0
0
The number and percentage of participants with Grade 2-4 acute GvHD in the prophylaxis phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.
Query!
Timepoint [31]
0
0
Days +30, +100, and +180 Post-HSCT
Query!
Secondary outcome [32]
0
0
Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Rescue Phase
Query!
Assessment method [32]
0
0
The number and percentage of participants with Grade 2-4 acute GvHD in the rescue phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.
Query!
Timepoint [32]
0
0
Days +30, +100, and +180 Post-HSCT
Query!
Secondary outcome [33]
0
0
Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Query!
Assessment method [33]
0
0
The values shown are the number and percentages of participants who developed chronic GvHD by Day +180 post-HSCT in the prophylaxis phase and rescue phase.
Query!
Timepoint [33]
0
0
Day +180 Post-HSCT
Query!
Secondary outcome [34]
0
0
Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase
Query!
Assessment method [34]
0
0
Graft failure is defined as participants that after hematopoietic stem cell transplant (HSCT) never reached an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days or a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination. For the subset of participants who developed VOD and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Query!
Timepoint [34]
0
0
Day +180 Post-HSCT
Query!
Secondary outcome [35]
0
0
Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Query!
Assessment method [35]
0
0
The date of neutrophil engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days. The definition of "absolute neutrophil count" includes both segmented neutrophils and "bands," immature neutrophils. The number of participants with neutrophil engraftment was assessed.
Query!
Timepoint [35]
0
0
Day +180 Post-HSCT
Query!
Secondary outcome [36]
0
0
Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Query!
Assessment method [36]
0
0
The date of platelet engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. The number of participants with platelet engraftment was assessed.
Query!
Timepoint [36]
0
0
Day +180 Post-HSCT
Query!
Eligibility
Key inclusion criteria
1. Patient must be above the age of 1 month as of the start date of study treatment.
2. Patient must be scheduled to undergo allogeneic hematopoietic stem cell transplant
(HSCT) (adults or pediatric patients) or autologous HSCT (pediatric patients only) and
be at high risk or very high risk of developing veno-occlusive disease (VOD).
3. Female patients (and female partners of male patients) of childbearing potential who
are sexually active must agree to use a highly effective method of contraception with
their partners during exposure to defibrotide and for 1 week after the last dose of
defibrotide.
4. Adult patients must be able to understand and sign a written informed consent. For
minor patients, the parent/legal guardian or representative must be able to understand
and sign a written informed consent. Assent, when appropriate, will be obtained
according to institutional guidelines.
Query!
Minimum age
1
Month
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
1. Patient has hemodynamic instability within 24 hours before the start of study
treatment.
2. Patient has acute bleeding that is clinically significant within 24 hours before the
start of study treatment.
3. Patient used any medication that increases the risk of bleeding within 24 hours before
the start of study treatment.
4. Patient is using or plans to use an investigational agent for the prevention or
treatment of VOD.
5. Patient, in the opinion of the investigator, may not be able to comply with the safety
monitoring requirements of the study.
6. Patient or parent/legal guardian or representative has a psychiatric illness that
would prevent the patient or parent/legal guardian or representative from giving
informed consent and/or assent.
7. Patient has a serious active disease or co-morbid medical condition, as judged by the
investigator, which would interfere with the conduct of this study.
8. Patient is pregnant or lactating and does not agree to stop breastfeeding.
9. Patient has a known history of hypersensitivity to defibrotide or any of the
excipients.
10. Patient or parent/legal guardian or representative lacks the full mental capacity to
understand and sign a written informed consent.
11. Patient is receiving or plans to receive other investigational therapy during study.
Query!
Study design
Purpose of the study
Prevention
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
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
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
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/09/2016
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
20/10/2020
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
372
Query!
Recruitment in Australia
Recruitment state(s)
SA,VIC
Query!
Recruitment hospital [1]
0
0
Royal Adelaide Hospital - Adelaide
Query!
Recruitment hospital [2]
0
0
Royal Children's Hospital Melbourne - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [2]
0
0
3052 - Melbourne
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
Delaware
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Florida
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Georgia
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Illinois
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Massachusetts
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Michigan
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Missouri
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
New York
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
North Carolina
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Ohio
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Oregon
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Pennsylvania
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
South Carolina
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Tennessee
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Texas
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Utah
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Washington
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Wisconsin
Query!
Country [23]
0
0
Belgium
Query!
State/province [23]
0
0
Bruxelles
Query!
Country [24]
0
0
Belgium
Query!
State/province [24]
0
0
Gent
Query!
Country [25]
0
0
Belgium
Query!
State/province [25]
0
0
Leuven
Query!
Country [26]
0
0
Belgium
Query!
State/province [26]
0
0
Liege
Query!
Country [27]
0
0
Canada
Query!
State/province [27]
0
0
Alberta
Query!
Country [28]
0
0
Canada
Query!
State/province [28]
0
0
Quebec
Query!
Country [29]
0
0
France
Query!
State/province [29]
0
0
Besançon
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Country [30]
0
0
France
Query!
State/province [30]
0
0
Marseille
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Country [31]
0
0
France
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State/province [31]
0
0
Paris
Query!
Country [32]
0
0
France
Query!
State/province [32]
0
0
Poitiers
Query!
Country [33]
0
0
France
Query!
State/province [33]
0
0
Toulouse
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Country [34]
0
0
Germany
Query!
State/province [34]
0
0
Brandenburg
Query!
Country [35]
0
0
Germany
Query!
State/province [35]
0
0
Nordrhein-Westfalen
Query!
Country [36]
0
0
Germany
Query!
State/province [36]
0
0
Sachsen
Query!
Country [37]
0
0
Germany
Query!
State/province [37]
0
0
Hamburg
Query!
Country [38]
0
0
Germany
Query!
State/province [38]
0
0
Regensburg
Query!
Country [39]
0
0
Israel
Query!
State/province [39]
0
0
Haifa
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Country [40]
0
0
Israel
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State/province [40]
0
0
Jerusalem
Query!
Country [41]
0
0
Israel
Query!
State/province [41]
0
0
Peta? Tiqwa
Query!
Country [42]
0
0
Israel
Query!
State/province [42]
0
0
Ramat Gan
Query!
Country [43]
0
0
Israel
Query!
State/province [43]
0
0
Tel Aviv
Query!
Country [44]
0
0
Italy
Query!
State/province [44]
0
0
Ancona
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
Catania
Query!
Country [46]
0
0
Italy
Query!
State/province [46]
0
0
Firenze
Query!
Country [47]
0
0
Italy
Query!
State/province [47]
0
0
Pesaro
Query!
Country [48]
0
0
Italy
Query!
State/province [48]
0
0
Roma
Query!
Country [49]
0
0
Japan
Query!
State/province [49]
0
0
Anjo
Query!
Country [50]
0
0
Japan
Query!
State/province [50]
0
0
Fukuoka
Query!
Country [51]
0
0
Japan
Query!
State/province [51]
0
0
Fukushima
Query!
Country [52]
0
0
Japan
Query!
State/province [52]
0
0
Hyogo
Query!
Country [53]
0
0
Japan
Query!
State/province [53]
0
0
Kanagawa
Query!
Country [54]
0
0
Japan
Query!
State/province [54]
0
0
Kumamoto
Query!
Country [55]
0
0
Japan
Query!
State/province [55]
0
0
Nagoya
Query!
Country [56]
0
0
Japan
Query!
State/province [56]
0
0
Nishinomiya
Query!
Country [57]
0
0
Japan
Query!
State/province [57]
0
0
Osaka
Query!
Country [58]
0
0
Japan
Query!
State/province [58]
0
0
Sapporo
Query!
Country [59]
0
0
Japan
Query!
State/province [59]
0
0
Tokyo
Query!
Country [60]
0
0
Korea, Republic of
Query!
State/province [60]
0
0
Seoul
Query!
Country [61]
0
0
New Zealand
Query!
State/province [61]
0
0
Auckland
Query!
Country [62]
0
0
Spain
Query!
State/province [62]
0
0
Barcelona
Query!
Country [63]
0
0
Spain
Query!
State/province [63]
0
0
Cordoba
Query!
Country [64]
0
0
Spain
Query!
State/province [64]
0
0
Esplugues de Llobregat
Query!
Country [65]
0
0
Spain
Query!
State/province [65]
0
0
Madrid
Query!
Country [66]
0
0
Spain
Query!
State/province [66]
0
0
Malaga
Query!
Country [67]
0
0
Spain
Query!
State/province [67]
0
0
Murcia
Query!
Country [68]
0
0
Spain
Query!
State/province [68]
0
0
Salamanca
Query!
Country [69]
0
0
Spain
Query!
State/province [69]
0
0
Sevilla
Query!
Country [70]
0
0
Turkey
Query!
State/province [70]
0
0
Konyaalti
Query!
Country [71]
0
0
Turkey
Query!
State/province [71]
0
0
Talas
Query!
Country [72]
0
0
Turkey
Query!
State/province [72]
0
0
Ankara
Query!
Country [73]
0
0
Turkey
Query!
State/province [73]
0
0
Antalya
Query!
Country [74]
0
0
Turkey
Query!
State/province [74]
0
0
Bornova
Query!
Country [75]
0
0
Turkey
Query!
State/province [75]
0
0
Istanbul
Query!
Country [76]
0
0
Turkey
Query!
State/province [76]
0
0
Seyhan
Query!
Country [77]
0
0
United Kingdom
Query!
State/province [77]
0
0
Birmingham
Query!
Country [78]
0
0
United Kingdom
Query!
State/province [78]
0
0
Glasgow
Query!
Country [79]
0
0
United Kingdom
Query!
State/province [79]
0
0
Leeds
Query!
Country [80]
0
0
United Kingdom
Query!
State/province [80]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Jazz Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This study is to compare the efficacy and safety of defibrotide prophylaxis in addition to
best supportive care versus best supportive care alone in the prevention of hepatic veno-
occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem cell
transplant who are at high risk or very high risk of developing VOD.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02851407
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Jazz Pharmaceuticals
Query!
Address
0
0
Jazz Pharmaceuticals
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/NCT02851407
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