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

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00628498
• Collaborator: (none)
• Enrollment: 1,206
• Locations: 125
• Arm: 1
• Duration (Months): 105
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Single arm, open-label study to provide Defibrotide to patients diagnosed with VOD. Defibrotide is no longer available though the Emergency Use IND mechanism (also known as compassionate use, or single patient named use). This protocol is the only mechanism by which Defibrotide can be made available to patients in the U.S.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Veno-Occlusive Disease	Drug: Defibrotide; Drug: Defibrotide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1206 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Defibrotide Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours

Drug: Defibrotide; Defibrotide is a single-stranded polydeoxyribonucleotide derived from porcine intestinal mucosa by controlled depolymerisation. Defibrotide has a complex mechanism of action with antithrombotic, anti-ischemic, anti-inflammatory, anti-adhesive and thrombolytic properties but no significant systemic anti-coagulant effects. Defibrotide is dose intravenously as a 2-hour infusion every 6 hours at a dose of 25 mg/kg/day. Recommended duration of therapy is 21 days.; Drug: Defibrotide

Outcome Measures

Primary Outcome Measures

1. Survival by Day+100 Post Stem Cell Transplant or Chemotherapy [Day +100 from HSCT or 100 days from start of chemotherapy]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Entry criteria include the following:

1. Clinical diagnosis of VOD, made by Baltimore Criteria, Modified Seattle Criteria, or biopsy proven:

1.1 Baltimore Criteria- Bilirubin ≥2 mg/dL and at least 2 of the following clinical findings:

• Ascites (radiographic or physical exam)

• Weight gain of ≥5% compared to the day of conditioning-- if this value is not available, the weight on the date of admission to the SCT unit may be used)

• Hepatomegaly; increased over baseline.

1.2 Modified Seattle Criteria: At least two of the following

• Bilirubin ≥2 mg/dL

• Ascites (radiographic or physical exam) and/or weight gain ≥5% above baseline weight (defined as weight on the first day of conditioning- if this value is not available, the weight on the date of admission to the SCT unit may be used)

• hepatomegaly increased over baseline

1.3 Patients that do not meet the Baltimore Criteria or Modified Seattle Criteria and have biopsy proven VOD are eligible.

1. Patient must also provide written informed consent.

Exclusion Criteria:

• Use of any medication which increases the risk of hemorrhage is disallowed. Use of heparin or other anticoagulants is disallowed within 12 hours unless being used for routine central venous line management, fibrinolytic instillation for central venous line occlusion, intermittent dialysis or ultrafiltration of CVVH.

• Clinically significant uncontrolled acute bleeding, defined as hemorrhage requiring > 15 cc/kg of packed red blood cells (e.g., a pediatric patient weighing 20 kg and requiring > 300cc of packed red blood cells/24 hours, or an adult patient weighing 70 kg and requiring >3 units of packed red blood cells/24 hours) to replace blood loss, OR bleeding from a site which in the Investigator's opinion constitutes a potential life-threatening source (e.g. pulmonary hemorrhage or CNS bleeding), irrespective of amount of blood loss, at any point from the date of SCT through the date of severe VOD diagnosis.

• Hemodynamic instability as defined by a requirement for multiple pressors, or inability to maintain mean arterial pressure (for children: to maintain mean arterial pressure within 1 standard deviation of age-adjusted levels) with single pressor support.

• Woman who are pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Mayo Clinic Cancer Center	Phoenix	Arizona	United States	85054
4	Arizona Oncology	Scottsdale	Arizona	United States	85258
5	University Medical Center	Tucson	Arizona	United States	85724
6	University of Arkansas for Medical Services	Little Rock	Arkansas	United States	72205
7	City of Hope Medical Center	Duarte	California	United States	91010
8	The University of California, San Diego	La Jolla	California	United States	92037
9	Loma Linda University	Loma Linda	California	United States	92354
10	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
11	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
12	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609
13	Children's Hospital of Orange County (CHOC)	Orange	California	United States	92868
14	Sutter Institute for Medical Research	Sacramento	California	United States	95816
15	University of California Davis Health System	Sacramento	California	United States	95817
16	Rady's Children's Hospital - San Diego	San Diego	California	United States	92123
17	University of California San Francisco Medical Center	San Francisco	California	United States	94143
18	Stanford University Medical Center	Stanford	California	United States	94305
19	Children's Hospital Colorado	Aurora	Colorado	United States	80045
20	US Oncology - Denver	Denver	Colorado	United States	80218
21	Yale - New Haven Hospital	New Haven	Connecticut	United States	06520
22	Nemours-Al duPont Hospital for Children	Wilmington	Delaware	United States	19803
23	Georgetown University Hospital	Washington	District of Columbia	United States	20007
24	Children's National Medical Center	Washington	District of Columbia	United States	20010
25	UF Health Shands Hospital	Gainesville	Florida	United States	32610
26	Jackson Memorial- University of Miami Health System- Pediatrics	Miami	Florida	United States	33136
27	Nicklaus Children's Hospital (Miami Children's Hospital)	Miami	Florida	United States	33155
28	Florida Hospital	Orlando	Florida	United States	42803
29	All Children's Hospital Specialty Physicians	Saint Petersburg	Florida	United States	33701
30	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
31	Childrens Healthcare of Atlanta	Atlanta	Georgia	United States	30322
32	Emory University Hospital	Atlanta	Georgia	United States	30322
33	Northside Hospital	Atlanta	Georgia	United States	30342
34	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
35	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
36	Northwest Memorial Hospital	Chicago	Illinois	United States	60611
37	Rush University Medical Center	Chicago	Illinois	United States	60612
38	Pediatric Hematology/Oncology MC4060 - University of Chicago	Chicago	Illinois	United States	60637
39	Cardinal Bernardin Cancer-Loyola University Medical Center	Maywood	Illinois	United States	60153
40	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
41	Indiana Blood and Marrow Transplantation Clinical Lab LLC/St. Francis Hospital	Indianapolis	Indiana	United States	46237
42	University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
43	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
44	Pediatric Blood and Cancer Disorders Clinic	Louisville	Kentucky	United States	40202
45	University of Louisville Research Foundation	Louisville	Kentucky	United States	40202
46	Tulane University Hospital & Clinic (Tuhc) - Tulane Cancer Center Comprehensive Clinic (Tcccc)	New Orleans	Louisiana	United States	70112
47	Children's Hospital	New Orleans	Louisiana	United States	70118
48	University of Maryland - Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
49	Johns Hopkins University	Baltimore	Maryland	United States	21287
50	National Institutes of Health	Bethesda	Maryland	United States	20892
51	Tufts Medical Center	Boston	Massachusetts	United States	02111
52	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
53	Boston Children's Hospital DFCI/CHB-Pediatrics	Boston	Massachusetts	United States	02115
54	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
55	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
56	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
57	Wayne State University/Children's Hospital of Michigan	Detroit	Michigan	United States	48201
58	Henry Ford Hospital	Detroit	Michigan	United States	48202
59	Helen DeVos Children's Hospital - Spectrum Health	Grand Rapids	Michigan	United States	49503
60	Children's Hospitals and Clinics of Minnesota and Minneapolis	Minneapolis	Minnesota	United States	55404
61	University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455
62	Mayo Clinic	Rochester	Minnesota	United States	55905
63	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
64	Children's Mercy Hospital and Clinics - Infectious Diseases	Kansas City	Missouri	United States	64108
65	Cardinal Glennon Children's Medical Center/St. Louis University Department of Pediatrics	Saint Louis	Missouri	United States	63104
66	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
67	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
68	Hackensack University Medical Center - Joseph M. Sanzari Childrens Hospital	Hackensack	New Jersey	United States	07601
69	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
70	Presbyterian Hospital	Albuquerque	New Mexico	United States	87106
71	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
72	Steven and Alexandra Cohen Children's Medical Center	New Hyde Park	New York	United States	11040
73	New York University School of Medicine	New York	New York	United States	10016
74	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
75	Mount Sinai Hospital - BMT Program	New York	New York	United States	10029
76	Mount Sinai Medical Center	New York	New York	United States	10029
77	Morgan Stanley Children's Hospital - Columbia University Medical Center	New York	New York	United States	10032
78	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York	United States	10065
79	University of Rochester Medical Center, Strong Memorial Hospital	Rochester	New York	United States	14642
80	Stony Brook University Hospital	Stony Brook	New York	United States	11794
81	Montefiore Medical Center	The Bronx	New York	United States	10467
82	New York Medical College	Valhalla	New York	United States	10595
83	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
84	Levine Children's Hospital	Charlotte	North Carolina	United States	28203
85	Duke University Medical Center	Durham	North Carolina	United States	27710
86	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
87	Children's Hospital Medical	Akron	Ohio	United States	44308
88	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
89	The Jewish Hospital	Cincinnati	Ohio	United States	45236
90	Case Western Reserve University (Cwru) - University Hospitals of Cleveland (Uhc)	Cleveland	Ohio	United States	44106
91	Robert J Tomsich Pathology & Laboratory Medicine Institute	Cleveland	Ohio	United States	44195
92	Nationwide Children's Hospital - Ohio State University College of Medicine (OSUCOM)	Columbus	Ohio	United States	43205
93	The Ohio State University, James Cancer Hospital	Columbus	Ohio	United States	43210
94	The University of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States	73104
95	Doernbecher Children's Hospital - Oregon Health and Science University	Portland	Oregon	United States	97239
96	Oregon Health and Science University	Portland	Oregon	United States	97239
97	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
98	Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
99	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
100	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15219
101	West Penn Allegheny Health System	Pittsburgh	Pennsylvania	United States	15224
102	Medical University of South Carolina	Charleston	South Carolina	United States	29425
103	Greenville Health System Cancer Institute	Greenville	South Carolina	United States	29605
104	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
105	Methodist University Hospital	Memphis	Tennessee	United States	38104
106	St. Jude Children's Research Hospital - Department of Bone Marrow Transplantation and Cellular Therapy	Memphis	Tennessee	United States	38105
107	The Children's Hospital at TriStar Centennial	Nashville	Tennessee	United States	37203
108	Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37232
109	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
110	San Antonio Military Medical Center	Fort Sam Houston	Texas	United States	78234
111	Cook Children's Health Care Hospital	Fort Worth	Texas	United States	76104
112	Baylor College of Medicine	Houston	Texas	United States	77030
113	Texas Children's Hospital	Houston	Texas	United States	77030
114	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
115	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
116	Methodist Healthcare System of San Antonio	San Antonio	Texas	United States	78229
117	University of Utah	Salt Lake City	Utah	United States	84132
118	University of Virginia Health System	Charlottesville	Virginia	United States	22908
119	Children's Hospital of the King's Daughter	Norfolk	Virginia	United States	23507
120	Virginia Commonwealth University	Richmond	Virginia	United States	23298
121	Fred Hutchinson Cancer Research Center/Seattle Children Hospital	Seattle	Washington	United States	98109
122	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
123	Mary Babb Randolph Cancer Center - West Virginia University Hospital	Morgantown	West Virginia	United States	26505
124	University of Wisconsin, American Family Children's Hospital, Medical School	Madison	Wisconsin	United States	53792
125	Medical College of Wisconsin/ Children's Hospitalof Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Study Chair: William Tappe, M.D., Jazz Pharmaceuticals
• Principal Investigator: Paul Richardson, M.D., Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00628498
• Other Study ID Numbers: P2006-05
• First Posted: Mar 5, 2008
• Last Update Posted: Nov 30, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Jazz Pharmaceuticals: VOD
• Additional relevant MeSH terms: Hepatic Veno-Occlusive Disease; Defibrotide

Study Results

Participant Flow

Arm/Group Title	Defibrotide
Arm/Group Description	Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Period Title: Overall Study
STARTED	1206
COMPLETED	1154
NOT COMPLETED	52

Baseline Characteristics

Arm/Group Title	Defibrotide
Arm/Group Description	Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Overall Participants	1154
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.32 (20.004)
Sex: Female, Male (Count of Participants)
Female	503 43.6%
Male	651 56.4%

Outcome Measures

1. Primary Outcome

Title	Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
Time Frame	Day +100 from HSCT or 100 days from start of chemotherapy

Outcome Measure Data

Analysis Population Description

ITT Efficacy Population

Arm/Group Title	Defibrotide
Arm/Group Description	Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Measure Participants	571
Number (95% Confidence Interval) [Percentage of participants alive]	49.9 4.3%

Adverse Events

Arm/Group Title	Defibrotide
Arm/Group Description	Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
All Cause Mortality
	Defibrotide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Defibrotide
	Affected / at Risk (%)	# Events
Total	598/1154 (51.8%)
Blood and lymphatic system disorders
Febrile neutropenia	6/1154 (0.5%)
Coagulopathy	5/1154 (0.4%)
Disseminated intravascular coagulation	5/1154 (0.4%)
Anaemia	2/1154 (0.2%)
Thrombocytopenia	2/1154 (0.2%)
Haemolysis	1/1154 (0.1%)
Haemolytic anaemia	1/1154 (0.1%)
Histiocytosis haematophagic	1/1154 (0.1%)
Pancytopenia	1/1154 (0.1%)
Thrombotic thrombocytopenic purpura	1/1154 (0.1%)
Cardiac disorders
Cardiac arrest	13/1154 (1.1%)
Cardio-respiratory arrest	9/1154 (0.8%)
Atrial flutter	8/1154 (0.7%)
Pericardial effusion	8/1154 (0.7%)
Bradycardia	6/1154 (0.5%)
Atrial fibrillation	5/1154 (0.4%)
Cardiac failure	4/1154 (0.3%)
Cardiopulmonary failure	3/1154 (0.3%)
Sinus bradycardia	3/1154 (0.3%)
Cardiac tamponade	2/1154 (0.2%)
Cardiomyopathy	2/1154 (0.2%)
Acute myocardial infarction	1/1154 (0.1%)
Atrial thrombosis	1/1154 (0.1%)
Atrioventricular block complete	1/1154 (0.1%)
Cardiac failure congestive	1/1154 (0.1%)
Right ventricular failure	1/1154 (0.1%)
Torsade de pointes	1/1154 (0.1%)
Ventricular fibrillation	1/1154 (0.1%)
Eye disorders
Retinal haemorrhage	1/1154 (0.1%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	33/1154 (2.9%)
Diarrhoea	9/1154 (0.8%)
Gastric haemorrhage	8/1154 (0.7%)
Ascites	7/1154 (0.6%)
Peritoneal haemorrhage	5/1154 (0.4%)
Abdominal pain	4/1154 (0.3%)
Lower gastrointestinal haemorrhage	4/1154 (0.3%)
Upper gastrointestinal haemorrhage	4/1154 (0.3%)
Intra-abdominal haemorrhage	3/1154 (0.3%)
Mouth haemorrhage	3/1154 (0.3%)
Pneumatosis intestinalis	3/1154 (0.3%)
Rectal haemorrhage	3/1154 (0.3%)
Colitis	2/1154 (0.2%)
Haematemesis	2/1154 (0.2%)
Abdominal compartment syndrome	1/1154 (0.1%)
Abdominal distension	1/1154 (0.1%)
Diarrhoea haemorrhagic	1/1154 (0.1%)
Enterocolitis	1/1154 (0.1%)
Haematochezia	1/1154 (0.1%)
Intestinal haemorrhage	1/1154 (0.1%)
Malabsorption	1/1154 (0.1%)
Nausea	1/1154 (0.1%)
Oesophageal ulcer haemorrhage	1/1154 (0.1%)
Pancreatitis	1/1154 (0.1%)
Retroperitoneal haemorrhage	1/1154 (0.1%)
Small intestinal haemorrhage	1/1154 (0.1%)
Vomiting	1/1154 (0.1%)
General disorders
Multi-organ failure	139/1154 (12%)
Pyrexia	11/1154 (1%)
Disease progression	2/1154 (0.2%)
Asthenia	1/1154 (0.1%)
Catheter site haemorrhage	1/1154 (0.1%)
Mucosal haemorrhage	1/1154 (0.1%)
Multi-organ disorder	1/1154 (0.1%)
Oedema	1/1154 (0.1%)
Oedema peripheral	1/1154 (0.1%)
Pneumatosis	1/1154 (0.1%)
Hepatobiliary disorders
Venoocclusive liver disease	87/1154 (7.5%)
Hepatic failure	19/1154 (1.6%)
Cholecystitis	4/1154 (0.3%)
Hepatorenal syndrome	3/1154 (0.3%)
Hepatic function abnormal	2/1154 (0.2%)
Acute hepatic failure	1/1154 (0.1%)
Bile duct obstruction	1/1154 (0.1%)
Cholecystitis acute	1/1154 (0.1%)
Hepatic cirrhosis	1/1154 (0.1%)
Hepatorenal failure	1/1154 (0.1%)
Hyperbilirubinaemia	1/1154 (0.1%)
Liver disorder	1/1154 (0.1%)
Portal vein thrombosis	1/1154 (0.1%)
Immune system disorders
Graft versus host disease	15/1154 (1.3%)
Acute graft versus host disease	6/1154 (0.5%)
Graft versus host disease in intestine	6/1154 (0.5%)
Graft versus host disease in liver	5/1154 (0.4%)
Graft versus host disease in skin	3/1154 (0.3%)
Acute graft versus host disease in intestine	1/1154 (0.1%)
Acute graft versus host disease in liver	1/1154 (0.1%)
Acute graft versus host disease in skin	1/1154 (0.1%)
Engraftment syndrome	1/1154 (0.1%)
Infections and infestations
Infection	17/1154 (1.5%)
Pneumonia	14/1154 (1.2%)
Septic shock	8/1154 (0.7%)
Lung infection	7/1154 (0.6%)
Cytomegalovirus infection	5/1154 (0.4%)
Bacteraemia	4/1154 (0.3%)
Pneumonia cytomegaloviral	4/1154 (0.3%)
BK virus infection	3/1154 (0.3%)
Bacterial sepsis	3/1154 (0.3%)
Device related infection	3/1154 (0.3%)
Pseudomonal bacteraemia	3/1154 (0.3%)
Sepsis syndrome	2/1154 (0.2%)
Staphylococcal bacteraemia	2/1154 (0.2%)
Staphylococcal infection	2/1154 (0.2%)
Urinary tract infection	2/1154 (0.2%)
Abdominal abscess	1/1154 (0.1%)
Abscess	1/1154 (0.1%)
Acid fast bacilli infection	1/1154 (0.1%)
Adenovirus infection	1/1154 (0.1%)
Appendicitis	1/1154 (0.1%)
Aspergillosis	1/1154 (0.1%)
Burkholderia cepacia complex infection	1/1154 (0.1%)
Candida sepsis	1/1154 (0.1%)
Cerebral fungal infection	1/1154 (0.1%)
Citrobacter sepsis	1/1154 (0.1%)
Clostridium difficile infection	1/1154 (0.1%)
Corona virus infection	1/1154 (0.1%)
Enterobacter bacteraemia	1/1154 (0.1%)
Enterobacter infection	1/1154 (0.1%)
Enterococcal bacteraemia	1/1154 (0.1%)
Enterococcal infection	1/1154 (0.1%)
Enterococcal sepsis	1/1154 (0.1%)
Enterocolitis infectious	1/1154 (0.1%)
Fungal infection	1/1154 (0.1%)
Fungal sepsis	1/1154 (0.1%)
Hepatitis viral	1/1154 (0.1%)
Human herpesvirus 6 infection	1/1154 (0.1%)
Lobar pneumonia	1/1154 (0.1%)
Neutropenic infection	1/1154 (0.1%)
Pneumocystis jiroveci pneumonia	1/1154 (0.1%)
Pneumonia parainfluenzae viral	1/1154 (0.1%)
Pneumonia respiratory syncytial viral	1/1154 (0.1%)
Pseudomonal sepsis	1/1154 (0.1%)
Pseudomonas infection	1/1154 (0.1%)
Respiratory syncytial virus infection	1/1154 (0.1%)
Septic embolus	1/1154 (0.1%)
Stenotrophomonas sepsis	1/1154 (0.1%)
Systemic candida	1/1154 (0.1%)
Toxoplasmosis	1/1154 (0.1%)
Varicella	1/1154 (0.1%)
Zygomycosis	1/1154 (0.1%)
Injury, poisoning and procedural complications
Sepsis	32/1154 (2.8%)
Transplant failure	5/1154 (0.4%)
Procedural haemorrhage	3/1154 (0.3%)
Brain herniation	2/1154 (0.2%)
Engraft failure	2/1154 (0.2%)
Subdural haematoma	2/1154 (0.2%)
Endotracheal intubation complication	1/1154 (0.1%)
Feeding tube complication	1/1154 (0.1%)
Hepatic haematoma	1/1154 (0.1%)
Overdose	1/1154 (0.1%)
Post procedural haemorrhage	1/1154 (0.1%)
Postoperative thoracic procedure complication	1/1154 (0.1%)
Procedural complication	1/1154 (0.1%)
Subdural haemorrhage	1/1154 (0.1%)
Tracheal haemorrhage	1/1154 (0.1%)
Transfusion-related acute lung injury	1/1154 (0.1%)
Investigations
Urine output decreased	3/1154 (0.3%)
Alanine aminotransferase increased	2/1154 (0.2%)
Aspartate aminotransferase increased	2/1154 (0.2%)
Blood bilirubin increased	2/1154 (0.2%)
Transaminases increased	2/1154 (0.2%)
Activated partial thromboplastin time prolonged	1/1154 (0.1%)
Blood creatinine increased	1/1154 (0.1%)
Gamma-glutamyltransferase increased	1/1154 (0.1%)
Human herpes virus 6 serology positive	1/1154 (0.1%)
International normalised ratio increased	1/1154 (0.1%)
Oxygen saturation decreased	1/1154 (0.1%)
Pulse absent	1/1154 (0.1%)
Weight increased	1/1154 (0.1%)
Metabolism and nutrition disorders
Hypokalaemia	6/1154 (0.5%)
Hypernatraemia	5/1154 (0.4%)
Acidosis	3/1154 (0.3%)
Fluid overload	3/1154 (0.3%)
Hyperkalaemia	3/1154 (0.3%)
Hyperammonaemia	2/1154 (0.2%)
Hyperglycaemia	2/1154 (0.2%)
Metabolic acidosis	2/1154 (0.2%)
Alkalosis	1/1154 (0.1%)
Hypocalcaemia	1/1154 (0.1%)
Hyponatraemia	1/1154 (0.1%)
Musculoskeletal and connective tissue disorders
Muscular weakness	2/1154 (0.2%)
Myopathy	1/1154 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia recurrent	4/1154 (0.3%)
Post transplant lymphoproliferative disorder	2/1154 (0.2%)
Acute lymphocytic leukaemia	1/1154 (0.1%)
Acute lymphocytic leukaemia recurrent	1/1154 (0.1%)
Acute myeloid leukaemia	1/1154 (0.1%)
Burkitt's lymphoma	1/1154 (0.1%)
Burkitt's lymphoma recurrent	1/1154 (0.1%)
Leukaemia recurrent	1/1154 (0.1%)
Mantle cell lymphoma	1/1154 (0.1%)
Myeloid leukaemia	1/1154 (0.1%)
Neuroblastoma recurrent	1/1154 (0.1%)
Recurrent cancer	1/1154 (0.1%)
Rhabdomyosarcoma	1/1154 (0.1%)
Sarcoma	1/1154 (0.1%)
T-cell lymphoma recurrent	1/1154 (0.1%)
Nervous system disorders
Encephalopathy	9/1154 (0.8%)
Haemorrhage intracranial	6/1154 (0.5%)
Convulsion	5/1154 (0.4%)
Cerebral ischaemia	3/1154 (0.3%)
Hepatic encephalopathy	3/1154 (0.3%)
Hydrocephalus	3/1154 (0.3%)
Subarachnoid haemorrhage	3/1154 (0.3%)
Central nervous system haemorrhage	2/1154 (0.2%)
Cerebral haemorrhage	2/1154 (0.2%)
Posterior reversible encephalopathy syndrome	2/1154 (0.2%)
Autonomic neuropathy	1/1154 (0.1%)
Brain hypoxia	1/1154 (0.1%)
Brain injury	1/1154 (0.1%)
Brain oedema	1/1154 (0.1%)
Cerebellar haematoma	1/1154 (0.1%)
Cerebral infarction	1/1154 (0.1%)
Cerebrovascular accident	1/1154 (0.1%)
Depressed level of consciousness	1/1154 (0.1%)
Facial nerve disorder	1/1154 (0.1%)
Hypertonia	1/1154 (0.1%)
Intraventricular haemorrhage	1/1154 (0.1%)
Neuropathy peripheral	1/1154 (0.1%)
Syncope	1/1154 (0.1%)
Psychiatric disorders
Confusional state	1/1154 (0.1%)
Mental status changes	1/1154 (0.1%)
Psychotic disorder	1/1154 (0.1%)
Renal and urinary disorders
Renal failure	45/1154 (3.9%)
Renal failure acute	22/1154 (1.9%)
Cystitis haemorrhagic	6/1154 (0.5%)
Renal impairment	2/1154 (0.2%)
Azotaemia	1/1154 (0.1%)
Haematuria	1/1154 (0.1%)
Urinary retention	1/1154 (0.1%)
Urogenital haemorrhage	1/1154 (0.1%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	80/1154 (6.9%)
Pulmonary haemorrhage	57/1154 (4.9%)
Hypoxia	31/1154 (2.7%)
Respiratory distress	22/1154 (1.9%)
Acute respiratory distress syndrome	16/1154 (1.4%)
Pulmonary alveolar haemorrhage	13/1154 (1.1%)
Epistaxis	7/1154 (0.6%)
Idiopathic pneumonia syndrome	6/1154 (0.5%)
Pulmonary oedema	6/1154 (0.5%)
Acute respiratory failure	5/1154 (0.4%)
Pleural effusion	5/1154 (0.4%)
Dyspnoea	4/1154 (0.3%)
Pneumonitis	4/1154 (0.3%)
Apnoea	3/1154 (0.3%)
Lung infiltration	3/1154 (0.3%)
Atelectasis	2/1154 (0.2%)
Diffuse alveolar damage	2/1154 (0.2%)
Haemothorax	2/1154 (0.2%)
Pulmonary hypertension	2/1154 (0.2%)
Tachypnoea	2/1154 (0.2%)
Alveolar proteinosis	1/1154 (0.1%)
Bronchial haemorrhage	1/1154 (0.1%)
Haemoptysis	1/1154 (0.1%)
Interstitial lung disease	1/1154 (0.1%)
Laryngeal stenosis	1/1154 (0.1%)
Pleural haemorrhage	1/1154 (0.1%)
Pneumonia aspiration	1/1154 (0.1%)
Pneumothorax	1/1154 (0.1%)
Pulmonary embolism	1/1154 (0.1%)
Pulmonary fibrosis	1/1154 (0.1%)
Pulmonary veno-occlusive disease	1/1154 (0.1%)
Respiratory arrest	1/1154 (0.1%)
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous	1/1154 (0.1%)
Rash maculo-papular	1/1154 (0.1%)
Vascular disorders
Hypotension	46/1154 (4%)
Venoocclusive disease	9/1154 (0.8%)
Haemorrhage	7/1154 (0.6%)
Hypertension	4/1154 (0.3%)
Circulatory collapse	2/1154 (0.2%)
Haematoma	2/1154 (0.2%)
Hypovolaemic shock	2/1154 (0.2%)
Capillary leak syndrome	1/1154 (0.1%)
Catheter site haemorrhage	1/1154 (0.1%)
Embolism	1/1154 (0.1%)
Haemorrhagic infarction	1/1154 (0.1%)
Hypertensive crisis	1/1154 (0.1%)
Microangiopathy	1/1154 (0.1%)
Shock	1/1154 (0.1%)
Other (Not Including Serious) Adverse Events
	Defibrotide
	Affected / at Risk (%)	# Events
Total	166/1154 (14.4%)
Gastrointestinal disorders
Diarrhoea	70/1154 (6.1%)
Vomiting	63/1154 (5.5%)
Vascular disorders
Hypotension	93/1154 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.