Study 2005-01
Study 2005-01 showed that defibrotide helped more people survive to day 100 after a stem-cell transplant when blocked liver veins had also led to kidney or lung failure, and it was the main evidence for the US approval of Defitelio.
Overview
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.
- 38.2 vs 25 out of 100 reached this endpoint with Defibrotide compared with Historical control; 13.2 more per 100.
- Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.0109) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- 25.5 vs 12.5 out of 100 had no sign of cancer on scans or tests with Defibrotide compared with Historical control; 13 more per 100.
- Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.0160) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 32.4 vs 25 out of 100 reached this endpoint with Defibrotide compared with Historical control; 7.4 more per 100.
- Roughly one extra person helped for every 14 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Severe hepatic veno-occlusive disease with multi-organ failure after stem-cell transplant: defibrotide in treated patients, compared with historical controls chosen by blinded review. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
134 enrolled.
Propensity-adjusted difference against historical control 23% (95.1% CI 5.2 to 40.8)
SourceDifference against historical control 19% (95.1% CI 3.5 to 34.6), same propensity-adjusted method
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Survival at day 100 after transplantprimary | Defibrotide | 102 | 38.2% | - | 0.0109 | link |
| Historical control | 32 | 25% | ||||
| Complete response by day 100 after transplant | Defibrotide | 102 | 25.5% | - | 0.0160 | link |
| Historical control | 32 | 12.5% | ||||
| Survival at day 180 after transplant | Defibrotide | 102 | 32.4% | - | - | link |
| Historical control | 32 | 25% |
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