Study 2005-01

Study 2005-01 was a multicentre, open-label, historically controlled phase 3 trial of defibrotide in adults and children with established hepatic veno-occlusive disease (sinusoidal obstruction syndrome) and advanced multi-organ failure after haematopoietic stem-cell transplant. One hundred and two patients received defibrotide at 25 mg per kilogram per day (6.25 mg per kilogram every six hours) for at least 21 days. They were compared with 32 historical controls, chosen by blinded independent reviewers from 6867 medical charts of transplant patients, and baseline characteristics were well balanced. The primary endpoint was survival at day 100 after transplant, using a propensity-adjusted analysis.

Day-100 survival was 38.2 percent with defibrotide and 25 percent in the historical controls (estimated difference 23 percent, 95.1% CI 5.2 to 40.8, P = .0109). Complete response by day 100 was 25.5 percent against 12.5 percent (difference 19 percent, 95.1% CI 3.5 to 34.6, P = .0160). Bleeding and low blood pressure were the related adverse events, and common bleeding events (pulmonary alveolar 11.8 against 15.6 percent, gastrointestinal 7.8 against 9.4 percent) occurred at similar rates in the two groups (Blood 2016). The registry results add day-180 survival of 32.4 against 25.0 percent.

The US label describes the same 102 patients as Study 1, reports their day-100 survival as 38 percent (95% CI 29 to 48) and bases the approval on it. The registry counts 134 participants (102 treated plus 32 controls) and records the study as completed. The FDA approved defibrotide (Defitelio) in March 2016 for hepatic veno-occlusive disease with renal or pulmonary dysfunction after transplant. The trial treats a complication of transplant rather than a cancer, so it carries no cancer ids.