Trial Outcomes & Findings for Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study (NCT NCT00628498)

NCT ID: NCT00628498

Last Updated: 2017-11-30

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1206 participants

Primary outcome timeframe

Day +100 from HSCT or 100 days from start of chemotherapy

Results posted on

2017-11-30

Participant Flow

Participant milestones

Participant milestones
Measure
Defibrotide
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Overall Study
STARTED
1206
Overall Study
COMPLETED
1154
Overall Study
NOT COMPLETED
52

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Defibrotide
n=1154 Participants
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Age, Continuous
19.32 years
STANDARD_DEVIATION 20.004 • n=5 Participants
Sex: Female, Male
Female
503 Participants
n=5 Participants
Sex: Female, Male
Male
651 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day +100 from HSCT or 100 days from start of chemotherapy

Population: ITT Efficacy Population

Outcome measures

Outcome measures
Measure
Defibrotide
n=571 Participants
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
49.9 Percentage of participants alive
Interval 45.8 to 54.0

Adverse Events

Defibrotide

Serious events: 598 serious events
Other events: 166 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Defibrotide
n=1154 participants at risk
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Blood and lymphatic system disorders
Febrile neutropenia
0.52%
6/1154
Blood and lymphatic system disorders
Coagulopathy
0.43%
5/1154
Blood and lymphatic system disorders
Disseminated intravascular coagulation
0.43%
5/1154
Blood and lymphatic system disorders
Anaemia
0.17%
2/1154
Blood and lymphatic system disorders
Thrombocytopenia
0.17%
2/1154
Blood and lymphatic system disorders
Haemolysis
0.09%
1/1154
Blood and lymphatic system disorders
Haemolytic anaemia
0.09%
1/1154
Blood and lymphatic system disorders
Histiocytosis haematophagic
0.09%
1/1154
Blood and lymphatic system disorders
Pancytopenia
0.09%
1/1154
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
0.09%
1/1154
Cardiac disorders
Cardiac arrest
1.1%
13/1154
Cardiac disorders
Cardio-respiratory arrest
0.78%
9/1154
Cardiac disorders
Atrial flutter
0.69%
8/1154
Cardiac disorders
Pericardial effusion
0.69%
8/1154
Cardiac disorders
Bradycardia
0.52%
6/1154
Cardiac disorders
Atrial fibrillation
0.43%
5/1154
Cardiac disorders
Cardiac failure
0.35%
4/1154
Cardiac disorders
Cardiopulmonary failure
0.26%
3/1154
Cardiac disorders
Sinus bradycardia
0.26%
3/1154
Cardiac disorders
Cardiac tamponade
0.17%
2/1154
Cardiac disorders
Cardiomyopathy
0.17%
2/1154
Cardiac disorders
Acute myocardial infarction
0.09%
1/1154
Cardiac disorders
Atrial thrombosis
0.09%
1/1154
Cardiac disorders
Atrioventricular block complete
0.09%
1/1154
Cardiac disorders
Cardiac failure congestive
0.09%
1/1154
Cardiac disorders
Right ventricular failure
0.09%
1/1154
Cardiac disorders
Torsade de pointes
0.09%
1/1154
Cardiac disorders
Ventricular fibrillation
0.09%
1/1154
Eye disorders
Retinal haemorrhage
0.09%
1/1154
Gastrointestinal disorders
Gastrointestinal haemorrhage
2.9%
33/1154
Gastrointestinal disorders
Diarrhoea
0.78%
9/1154
Gastrointestinal disorders
Gastric haemorrhage
0.69%
8/1154
Gastrointestinal disorders
Ascites
0.61%
7/1154
Gastrointestinal disorders
Peritoneal haemorrhage
0.43%
5/1154
Gastrointestinal disorders
Abdominal pain
0.35%
4/1154
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
0.35%
4/1154
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
0.35%
4/1154
Gastrointestinal disorders
Intra-abdominal haemorrhage
0.26%
3/1154
Gastrointestinal disorders
Mouth haemorrhage
0.26%
3/1154
Gastrointestinal disorders
Pneumatosis intestinalis
0.26%
3/1154
Gastrointestinal disorders
Rectal haemorrhage
0.26%
3/1154
Gastrointestinal disorders
Colitis
0.17%
2/1154
Gastrointestinal disorders
Haematemesis
0.17%
2/1154
Gastrointestinal disorders
Abdominal compartment syndrome
0.09%
1/1154
Gastrointestinal disorders
Abdominal distension
0.09%
1/1154
Gastrointestinal disorders
Diarrhoea haemorrhagic
0.09%
1/1154
Gastrointestinal disorders
Enterocolitis
0.09%
1/1154
Gastrointestinal disorders
Haematochezia
0.09%
1/1154
Gastrointestinal disorders
Intestinal haemorrhage
0.09%
1/1154
Gastrointestinal disorders
Malabsorption
0.09%
1/1154
Gastrointestinal disorders
Nausea
0.09%
1/1154
Gastrointestinal disorders
Oesophageal ulcer haemorrhage
0.09%
1/1154
Gastrointestinal disorders
Pancreatitis
0.09%
1/1154
Gastrointestinal disorders
Retroperitoneal haemorrhage
0.09%
1/1154
Gastrointestinal disorders
Small intestinal haemorrhage
0.09%
1/1154
Gastrointestinal disorders
Vomiting
0.09%
1/1154
General disorders
Multi-organ failure
12.0%
139/1154
General disorders
Pyrexia
0.95%
11/1154
General disorders
Disease progression
0.17%
2/1154
General disorders
Asthenia
0.09%
1/1154
General disorders
Catheter site haemorrhage
0.09%
1/1154
General disorders
Mucosal haemorrhage
0.09%
1/1154
General disorders
Multi-organ disorder
0.09%
1/1154
General disorders
Oedema
0.09%
1/1154
General disorders
Oedema peripheral
0.09%
1/1154
General disorders
Pneumatosis
0.09%
1/1154
Hepatobiliary disorders
Venoocclusive liver disease
7.5%
87/1154
Hepatobiliary disorders
Hepatic failure
1.6%
19/1154
Hepatobiliary disorders
Cholecystitis
0.35%
4/1154
Hepatobiliary disorders
Hepatorenal syndrome
0.26%
3/1154
Hepatobiliary disorders
Hepatic function abnormal
0.17%
2/1154
Hepatobiliary disorders
Acute hepatic failure
0.09%
1/1154
Hepatobiliary disorders
Bile duct obstruction
0.09%
1/1154
Hepatobiliary disorders
Cholecystitis acute
0.09%
1/1154
Hepatobiliary disorders
Hepatic cirrhosis
0.09%
1/1154
Hepatobiliary disorders
Hepatorenal failure
0.09%
1/1154
Hepatobiliary disorders
Hyperbilirubinaemia
0.09%
1/1154
Hepatobiliary disorders
Liver disorder
0.09%
1/1154
Hepatobiliary disorders
Portal vein thrombosis
0.09%
1/1154
Immune system disorders
Graft versus host disease
1.3%
15/1154
Immune system disorders
Acute graft versus host disease
0.52%
6/1154
Immune system disorders
Graft versus host disease in intestine
0.52%
6/1154
Immune system disorders
Graft versus host disease in liver
0.43%
5/1154
Immune system disorders
Graft versus host disease in skin
0.26%
3/1154
Immune system disorders
Acute graft versus host disease in intestine
0.09%
1/1154
Immune system disorders
Acute graft versus host disease in liver
0.09%
1/1154
Immune system disorders
Acute graft versus host disease in skin
0.09%
1/1154
Immune system disorders
Engraftment syndrome
0.09%
1/1154
Injury, poisoning and procedural complications
Sepsis
2.8%
32/1154
Infections and infestations
Infection
1.5%
17/1154
Infections and infestations
Pneumonia
1.2%
14/1154
Infections and infestations
Septic shock
0.69%
8/1154
Infections and infestations
Lung infection
0.61%
7/1154
Infections and infestations
Cytomegalovirus infection
0.43%
5/1154
Infections and infestations
Bacteraemia
0.35%
4/1154
Infections and infestations
Pneumonia cytomegaloviral
0.35%
4/1154
Infections and infestations
BK virus infection
0.26%
3/1154
Infections and infestations
Bacterial sepsis
0.26%
3/1154
Infections and infestations
Device related infection
0.26%
3/1154
Infections and infestations
Pseudomonal bacteraemia
0.26%
3/1154
Infections and infestations
Sepsis syndrome
0.17%
2/1154
Infections and infestations
Staphylococcal bacteraemia
0.17%
2/1154
Infections and infestations
Staphylococcal infection
0.17%
2/1154
Infections and infestations
Urinary tract infection
0.17%
2/1154
Infections and infestations
Abdominal abscess
0.09%
1/1154
Infections and infestations
Abscess
0.09%
1/1154
Infections and infestations
Acid fast bacilli infection
0.09%
1/1154
Infections and infestations
Adenovirus infection
0.09%
1/1154
Infections and infestations
Appendicitis
0.09%
1/1154
Infections and infestations
Aspergillosis
0.09%
1/1154
Infections and infestations
Burkholderia cepacia complex infection
0.09%
1/1154
Infections and infestations
Candida sepsis
0.09%
1/1154
Infections and infestations
Cerebral fungal infection
0.09%
1/1154
Infections and infestations
Citrobacter sepsis
0.09%
1/1154
Infections and infestations
Clostridium difficile infection
0.09%
1/1154
Infections and infestations
Corona virus infection
0.09%
1/1154
Infections and infestations
Enterobacter bacteraemia
0.09%
1/1154
Infections and infestations
Enterobacter infection
0.09%
1/1154
Infections and infestations
Enterococcal bacteraemia
0.09%
1/1154
Infections and infestations
Enterococcal infection
0.09%
1/1154
Infections and infestations
Enterococcal sepsis
0.09%
1/1154
Infections and infestations
Enterocolitis infectious
0.09%
1/1154
Infections and infestations
Fungal infection
0.09%
1/1154
Infections and infestations
Fungal sepsis
0.09%
1/1154
Infections and infestations
Hepatitis viral
0.09%
1/1154
Infections and infestations
Human herpesvirus 6 infection
0.09%
1/1154
Infections and infestations
Lobar pneumonia
0.09%
1/1154
Infections and infestations
Neutropenic infection
0.09%
1/1154
Infections and infestations
Pneumocystis jiroveci pneumonia
0.09%
1/1154
Infections and infestations
Pneumonia parainfluenzae viral
0.09%
1/1154
Infections and infestations
Pneumonia respiratory syncytial viral
0.09%
1/1154
Infections and infestations
Pseudomonal sepsis
0.09%
1/1154
Infections and infestations
Pseudomonas infection
0.09%
1/1154
Infections and infestations
Respiratory syncytial virus infection
0.09%
1/1154
Infections and infestations
Septic embolus
0.09%
1/1154
Infections and infestations
Stenotrophomonas sepsis
0.09%
1/1154
Infections and infestations
Systemic candida
0.09%
1/1154
Infections and infestations
Toxoplasmosis
0.09%
1/1154
Infections and infestations
Varicella
0.09%
1/1154
Infections and infestations
Zygomycosis
0.09%
1/1154
Injury, poisoning and procedural complications
Transplant failure
0.43%
5/1154
Injury, poisoning and procedural complications
Procedural haemorrhage
0.26%
3/1154
Injury, poisoning and procedural complications
Brain herniation
0.17%
2/1154
Injury, poisoning and procedural complications
Engraft failure
0.17%
2/1154
Injury, poisoning and procedural complications
Subdural haematoma
0.17%
2/1154
Injury, poisoning and procedural complications
Endotracheal intubation complication
0.09%
1/1154
Injury, poisoning and procedural complications
Feeding tube complication
0.09%
1/1154
Injury, poisoning and procedural complications
Hepatic haematoma
0.09%
1/1154
Injury, poisoning and procedural complications
Overdose
0.09%
1/1154
Injury, poisoning and procedural complications
Post procedural haemorrhage
0.09%
1/1154
Injury, poisoning and procedural complications
Postoperative thoracic procedure complication
0.09%
1/1154
Injury, poisoning and procedural complications
Procedural complication
0.09%
1/1154
Injury, poisoning and procedural complications
Subdural haemorrhage
0.09%
1/1154
Injury, poisoning and procedural complications
Tracheal haemorrhage
0.09%
1/1154
Injury, poisoning and procedural complications
Transfusion-related acute lung injury
0.09%
1/1154
Investigations
Urine output decreased
0.26%
3/1154
Investigations
Alanine aminotransferase increased
0.17%
2/1154
Investigations
Aspartate aminotransferase increased
0.17%
2/1154
Investigations
Blood bilirubin increased
0.17%
2/1154
Investigations
Transaminases increased
0.17%
2/1154
Investigations
Activated partial thromboplastin time prolonged
0.09%
1/1154
Investigations
Blood creatinine increased
0.09%
1/1154
Investigations
Gamma-glutamyltransferase increased
0.09%
1/1154
Investigations
Human herpes virus 6 serology positive
0.09%
1/1154
Investigations
International normalised ratio increased
0.09%
1/1154
Investigations
Oxygen saturation decreased
0.09%
1/1154
Investigations
Pulse absent
0.09%
1/1154
Investigations
Weight increased
0.09%
1/1154
Metabolism and nutrition disorders
Hypokalaemia
0.52%
6/1154
Metabolism and nutrition disorders
Hypernatraemia
0.43%
5/1154
Metabolism and nutrition disorders
Acidosis
0.26%
3/1154
Metabolism and nutrition disorders
Fluid overload
0.26%
3/1154
Metabolism and nutrition disorders
Hyperkalaemia
0.26%
3/1154
Metabolism and nutrition disorders
Hyperammonaemia
0.17%
2/1154
Metabolism and nutrition disorders
Hyperglycaemia
0.17%
2/1154
Metabolism and nutrition disorders
Metabolic acidosis
0.17%
2/1154
Metabolism and nutrition disorders
Alkalosis
0.09%
1/1154
Metabolism and nutrition disorders
Hypocalcaemia
0.09%
1/1154
Metabolism and nutrition disorders
Hyponatraemia
0.09%
1/1154
Musculoskeletal and connective tissue disorders
Muscular weakness
0.17%
2/1154
Musculoskeletal and connective tissue disorders
Myopathy
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia recurrent
0.35%
4/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Post transplant lymphoproliferative disorder
0.17%
2/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma recurrent
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia recurrent
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myeloid leukaemia
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroblastoma recurrent
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Recurrent cancer
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rhabdomyosarcoma
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sarcoma
0.09%
1/1154
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
T-cell lymphoma recurrent
0.09%
1/1154
Nervous system disorders
Encephalopathy
0.78%
9/1154
Nervous system disorders
Haemorrhage intracranial
0.52%
6/1154
Nervous system disorders
Convulsion
0.43%
5/1154
Nervous system disorders
Cerebral ischaemia
0.26%
3/1154
Nervous system disorders
Hepatic encephalopathy
0.26%
3/1154
Nervous system disorders
Hydrocephalus
0.26%
3/1154
Nervous system disorders
Subarachnoid haemorrhage
0.26%
3/1154
Nervous system disorders
Central nervous system haemorrhage
0.17%
2/1154
Nervous system disorders
Cerebral haemorrhage
0.17%
2/1154
Nervous system disorders
Posterior reversible encephalopathy syndrome
0.17%
2/1154
Nervous system disorders
Autonomic neuropathy
0.09%
1/1154
Nervous system disorders
Brain hypoxia
0.09%
1/1154
Nervous system disorders
Brain injury
0.09%
1/1154
Nervous system disorders
Brain oedema
0.09%
1/1154
Nervous system disorders
Cerebellar haematoma
0.09%
1/1154
Nervous system disorders
Cerebral infarction
0.09%
1/1154
Nervous system disorders
Cerebrovascular accident
0.09%
1/1154
Nervous system disorders
Depressed level of consciousness
0.09%
1/1154
Nervous system disorders
Facial nerve disorder
0.09%
1/1154
Nervous system disorders
Hypertonia
0.09%
1/1154
Nervous system disorders
Intraventricular haemorrhage
0.09%
1/1154
Nervous system disorders
Neuropathy peripheral
0.09%
1/1154
Nervous system disorders
Syncope
0.09%
1/1154
Psychiatric disorders
Confusional state
0.09%
1/1154
Psychiatric disorders
Mental status changes
0.09%
1/1154
Psychiatric disorders
Psychotic disorder
0.09%
1/1154
Renal and urinary disorders
Renal failure
3.9%
45/1154
Renal and urinary disorders
Renal failure acute
1.9%
22/1154
Renal and urinary disorders
Cystitis haemorrhagic
0.52%
6/1154
Renal and urinary disorders
Renal impairment
0.17%
2/1154
Renal and urinary disorders
Azotaemia
0.09%
1/1154
Renal and urinary disorders
Haematuria
0.09%
1/1154
Renal and urinary disorders
Urinary retention
0.09%
1/1154
Renal and urinary disorders
Urogenital haemorrhage
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Respiratory failure
6.9%
80/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
4.9%
57/1154
Respiratory, thoracic and mediastinal disorders
Hypoxia
2.7%
31/1154
Respiratory, thoracic and mediastinal disorders
Respiratory distress
1.9%
22/1154
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
1.4%
16/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
1.1%
13/1154
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.61%
7/1154
Respiratory, thoracic and mediastinal disorders
Idiopathic pneumonia syndrome
0.52%
6/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
0.52%
6/1154
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
0.43%
5/1154
Respiratory, thoracic and mediastinal disorders
Pleural effusion
0.43%
5/1154
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.35%
4/1154
Respiratory, thoracic and mediastinal disorders
Pneumonitis
0.35%
4/1154
Respiratory, thoracic and mediastinal disorders
Apnoea
0.26%
3/1154
Respiratory, thoracic and mediastinal disorders
Lung infiltration
0.26%
3/1154
Respiratory, thoracic and mediastinal disorders
Atelectasis
0.17%
2/1154
Respiratory, thoracic and mediastinal disorders
Diffuse alveolar damage
0.17%
2/1154
Respiratory, thoracic and mediastinal disorders
Haemothorax
0.17%
2/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
0.17%
2/1154
Respiratory, thoracic and mediastinal disorders
Tachypnoea
0.17%
2/1154
Respiratory, thoracic and mediastinal disorders
Alveolar proteinosis
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Bronchial haemorrhage
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Haemoptysis
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Laryngeal stenosis
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pleural haemorrhage
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pneumothorax
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Pulmonary veno-occlusive disease
0.09%
1/1154
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
0.09%
1/1154
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
0.09%
1/1154
Skin and subcutaneous tissue disorders
Rash maculo-papular
0.09%
1/1154
Vascular disorders
Hypotension
4.0%
46/1154
Vascular disorders
Venoocclusive disease
0.78%
9/1154
Vascular disorders
Haemorrhage
0.61%
7/1154
Vascular disorders
Hypertension
0.35%
4/1154
Vascular disorders
Circulatory collapse
0.17%
2/1154
Vascular disorders
Haematoma
0.17%
2/1154
Vascular disorders
Hypovolaemic shock
0.17%
2/1154
Vascular disorders
Capillary leak syndrome
0.09%
1/1154
Vascular disorders
Catheter site haemorrhage
0.09%
1/1154
Vascular disorders
Embolism
0.09%
1/1154
Vascular disorders
Haemorrhagic infarction
0.09%
1/1154
Vascular disorders
Hypertensive crisis
0.09%
1/1154
Vascular disorders
Microangiopathy
0.09%
1/1154
Vascular disorders
Shock
0.09%
1/1154

Other adverse events

Other adverse events
Measure
Defibrotide
n=1154 participants at risk
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Vascular disorders
Hypotension
8.1%
93/1154
Gastrointestinal disorders
Diarrhoea
6.1%
70/1154
Gastrointestinal disorders
Vomiting
5.5%
63/1154

Additional Information

Associate Director, Clinical Trial Disclosure & Transparency

Jazz Pharmaceuticals

Phone: (215) 832-3750

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place