Chapter 7 164 Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease: Final Results From the International Compassionate Use Program Setup The expanded access program was a multicenter, multinational program, including both group access programs as well as single-patient emergency requests. Data collection was not driven by a protocol, but physicians were asked to complete prospective structured data collection forms at baseline, and outcome (survival) data. Physicians were responsible for obtaining appropriate approval from ethics committee and obtaining patient consent. The program was conducted from December 1998 to March 2009. The study was funded by the sponsor, Jazz Pharmaceuticals, including support for medical writing and manuscript editing. Patients The expanded access program was open to patients with hepatic veno-occlusive disease (VOD) after receiving a hematopoietic stem cell transplant. VOD is also known as sinusoidal obstruction syndrome (SOS) and may typically present with multiorgan failure. In total, 1129 patients from 311 sites participated in the expanded access program. Forty-three percent of all patients were under 18 years of age. The analysis population comprised of all patients from which forms were voluntarily returned by physicians, N=710. Patients had a median age of 25 years (range, 0.2–70.0). Intervention Patients received defibrotide, an oligonucleotide. At the start of the expanded access program, patients were dosed 10 mg/kg/day, but as soon as data the phase II study became available, the dose was amended to 25 mg/kg/day. Treatment duration was freely determined by the treating physician, with a minimum recommended treatment duration of 14 days. Outcome Patients received defibrotide for a median of 15 days (range 1-119). Fifty-one percent of all patients experienced at least one serious adverse event. The primary efficacy outcome was 100-day survival status after date of stem cell transplant. The overall survival estimate in this expanded access program at 100-days was 54% (95% 50.2, 58.0). Comparison/interpretation by the authors Although patients may have been different from trial patients, as ‘The study included a heterogeneous population of patients with VOD/SOS, in part because of the real-world nature of the program and in part of differences in inclusion criteria in different regions’, the authors note that ‘The day +100 survival and safety profiles in this study are notably consistent with those reported in other defibrotide studies’, and in detail discuss similarities across outcomes even in identified subgroups.
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