Jazz Pharmaceuticals plc announced that the first patient has been enrolled in a Phase 3 clinical trial comparing the efficacy and safety of defibrotide versus best supportive care (BSC) in the prevention of hepatic veno-occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem cell transplant (HSCT) who are at high risk or at very high risk of developing VOD. The defibrotide clinical trial will be conducted across approximately 100 medical centers in the United States (U.S.), Canada, Asia Pacific and countries in the European Union (EU). The Phase 3 trial is a randomized, open-label, multi-center trial with an adaptive design comparing the efficacy of defibrotide vs. BSC in the prevention of hepatic VOD. The trial is expected to enroll approximately 400 adult and pediatric patients undergoing HSCT who are at high risk or very high risk of developing VOD. High (or very high) risk patients are identified due to the clinical regimen required to prepare them for HSCT, as well as their prior medical history and concomitant disease. The adaptive design allows for an interim analysis with pre-defined stopping points for early success or failure as well as the option to increase enrollment if needed to preserve the statistical power of the trial. Defibrotide has orphan drug designation from the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the prevention of hepatic VOD. In the U.S. Defitelio® (defibrotide sodium) injection 80mg/mL received U.S.FDA marketing approval on March 30, 2016 for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication. Defitelio is contraindicated in patients currently taking anticoagulants or fibrinolytics and in patients who are allergic to Defitelio or any of its ingredients. Defitelio may increase the risk of bleeding and should be withheld or stopped if significant bleeding occurs. Patients should be monitored for allergic reactions, especially if there is a history of previous exposure to Defitelio. The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds. HSCT is an aggressive, potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, and congenital immunodeficiency and autoimmune disorders.  VOD is a rare complication of HSCT, which occurs in approximately 9-14% of HSCT patients.  Hepatic VOD, also known as SOS, is an early and life-threatening complication affecting the sinusoidal endothelial cells of the liver, which can typically occur within the first 21 days following HSCT.  Hepatic VOD progresses to multi-organ dysfunction in approximately 30-50% of cases.  VOD with multi-organ dysfunction (MOD) is associated with an overall mortality (death) rate of 84%.  MOD is characterized by the presence of renal or pulmonary dysfunction.  VOD is often characterized by sudden weight gain, hepatomegaly (abnormally enlarged liver), and elevated bilirubin.