{"entity":{"id":"paper-defibrotide-2005-01-blood-2016","kind":"paper","name":"Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure","aka":[],"tldr":"The primary report of Study 2005-01: 38 percent of transplant patients with severe veno-occlusive disease and organ failure were alive at day 100 on defibrotide, against 25 percent of carefully matched historical controls.","summary":"Phase 3 study of defibrotide in patients with established hepatic veno-occlusive disease (sinusoidal obstruction syndrome) and advanced multi-organ failure after haematopoietic stem cell transplantation, a condition with more than 80 percent mortality untreated. Patients (n = 102) given defibrotide 25 mg per kilogram per day were compared with 32 historical controls identified from 6867 medical charts of transplant patients by blinded independent reviewers; baseline characteristics were well balanced.\n\nThe primary endpoint was survival at day +100 post-transplant: observed rates were 38.2 percent in the defibrotide group and 25 percent in the controls (23 percent estimated difference; 95.1% CI 5.2 to 40.8; P = .0109, propensity-adjusted analysis). Observed day +100 complete response rates were 25.5 percent for defibrotide and 12.5 percent for controls (19 percent difference; 95.1% CI 3.5 to 34.6; P = .0160). Related adverse events included haemorrhage or hypotension; common haemorrhagic events (pulmonary alveolar 11.8 and 15.6 percent, gastrointestinal 7.8 and 9.4 percent) were similar between groups.","asOf":"2026-09-24","links":[{"label":"Blood 2016","url":"https://doi.org/10.1182/blood-2015-10-676924"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26825712/"},{"label":"ClinicalTrials.gov NCT00358501","url":"https://clinicaltrials.gov/study/NCT00358501"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["defibrotide"],"companies":["jazz"],"institutions":[],"pathways":[],"terms":["allogeneic-transplant"],"trials":["study-2005-01"],"people":["paul-richardson"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2016,"doi":"10.1182/blood-2015-10-676924","pmid":"26825712","authors":"Richardson PG, Riches ML, Kernan NA, et al.","paperType":"observational","findings":["Day +100 survival 38.2% with defibrotide vs 25% in historical controls; estimated difference 23% (95.1% CI 5.2 to 40.8), P = .0109.","Day +100 complete response 25.5% vs 12.5%; difference 19% (95.1% CI 3.5 to 34.6), P = .0160.","Haemorrhagic adverse events similar between groups: pulmonary alveolar bleeding 11.8% vs 15.6%, gastrointestinal bleeding 7.8% vs 9.4%."],"whatItMeans":"This is the trial behind defibrotide's March 2016 US approval, the only approved treatment for hepatic veno-occlusive disease with organ failure after transplant. The historical-control design was accepted because a randomised trial in a condition this lethal and rare was judged unfeasible; the gain is meaningful but most patients still died.","caveats":["Historically controlled, not randomised; the 32 controls were matched from chart review.","95.1% confidence intervals adjust for an interim analysis.","Absolute survival remained low (38% at day 100)."],"changedPractice":true,"participants":134},"route":"/key-papers/paper-defibrotide-2005-01-blood-2016/","neighbours":{"drug":[{"id":"defibrotide","kind":"drug","name":"Defibrotide","route":"/drugs/defibrotide/"}],"company":[{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"}],"term":[{"id":"allogeneic-transplant","kind":"term","name":"Allogeneic stem cell transplant (allo-SCT)","route":"/terms/allogeneic-transplant/"}],"trial":[{"id":"study-2005-01","kind":"trial","name":"Study 2005-01","route":"/trials/study-2005-01/"}],"person":[{"id":"paul-richardson","kind":"person","name":"Paul G. Richardson","route":"/people/paul-richardson/"}],"journal":[{"id":"blood","kind":"journal","name":"Blood","route":"/journals/blood/"}]}}