# Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

Source: https://onco.cc/key-papers/paper-defibrotide-2005-01-blood-2016/  
OnCo record `paper-defibrotide-2005-01-blood-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Blood
- Year: 2016
- DOI: 10.1182/blood-2015-10-676924
- Authors: Richardson PG, Riches ML, Kernan NA, et al.
- 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%.
- What it means: 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).

## Sources

- Blood 2016: https://doi.org/10.1182/blood-2015-10-676924
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26825712/
- ClinicalTrials.gov NCT00358501: https://clinicaltrials.gov/study/NCT00358501

## Connected records

- drugs: [Defibrotide](https://onco.cc/drugs/defibrotide/)
- companies: [Jazz Pharmaceuticals](https://onco.cc/companies/jazz/)
- terms: [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/)
- trials: [Study 2005-01](https://onco.cc/trials/study-2005-01/)
- people: [Paul G. Richardson](https://onco.cc/people/paul-richardson/)
- journals: [Blood](https://onco.cc/journals/blood/)

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