Protocols

Determination of the Optimal Prophylactic Platelet Dose to Prevent Bleeding in Thrombocytopenic Patients (PLADO)
The PLADO study was a randomized trial comparing three doses (lower dose, medium dose, and higher dose) for prophylactic platelet transfusions in patients with thrombocytopenia due to stem cell transplant or chemotherapy.  The primary outcome was the percentage of patients who had at least one day of Grade 2 or higher bleeding according to the WHO scale.  Key secondary outcomes included highest grade of bleeding, total number of platelets transfused, and number of transfusion events.  The trial was completed in January 2008 with 1351 subjects enrolled.  There were no significant differences between treatment arms in the primary endpoint.  Further results will be presented at educational sessions at AABB and ASH, an abstract has been submitted for ASH, and analysis and writing of the primary results manuscript is well underway.

Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (RICH)
The RICH study is a single-arm, Phase II study of rituximab treatment for patients with congenital hemophilia A and high-titer inhibitors to Factor VIII.  Eligible subjects with a history of high-titer inhibitors receive a challenge dose of Factor VIII.  Those whose post-challenge inhibitor titer is at least 5 Bethesda Units are eligible for the treatment phase of the study, which consists of rituximab infusions given weekly for four weeks.  The primary endpoint is the percentage of subjects who have a post-treatment inhibitor titer of < 5 Bethesda Units, and remain at < 5 Bethesda Units after another challenge with Factor VIII.  The planned enrollment target is 43 subjects who receive at least one dose of rituximab.  The study is ongoing.

Heparin Induced Thrombocytopenia Observational Thromboembolism Study (HOT)
The HOT study is an observational study of hospital in-patients diagnosed with isolated Heparin Induced Thrombocytopenia (i.e. diagnosed with HIT, but with no known thrombosis since the initiation of the current round of heparin treatment).  The primary endpoint is the percentage of patients who have a thrombosis at entry into the study, as determined by 4-limb ultrasound (plus abdominal ultrasound for patients less than 7 years of age).  The key secondary endpoints are development of symptomatic thrombosis by the end of the study (day 35 ± 7 days), and thrombosis as detected by ultrasound at the end of the study.  The study began enrollment in February 2008 and is ongoing.

Resolving Infection in Neutropenia with Granulocytes (RING)
The RING study is a randomized trial enrolling patients who are neutropenic following chemotherapy or stem cell transplant, and have a probable or definite bacterial or fungal infection.  One group of patients will be treated with antimicrobial therapy alone, and the other group will be treated with antimicrobial therapy plus GCSF-stimulated granulocyte transfusions.  The primary outcome is the percentage of patients who are alive at 42 days after study entry, AND have had their infection resolve or improve.  The target enrollment is 236.  The study began enrollment in August 2008 and is ongoing.

Study of TTP and Rituximab (STAR)
The STAR study is a randomized trial of rituximab as early treatment for Thrombotic Thrombocytopenic Purpura (TTP).  It will enroll patients who have recently been diagnosed with TTP or recently experienced a relapse, and have not yet had 6 plasma exchanges during this episode of TTP.  One group of patients will be treated with plasma exchange and corticosteroids.  The other group will be treated with plasma exchange, corticosteroids, and four weekly infusions of rituximab.  The primary outcome is the percentage of patients who experience an early treatment response (off plasma exchange by day 22, and remaining off plasma exchange for 30 days).  Key secondary outcomes are the percentage of patients who experience late treatment response, the percentage who relapse, and laboratory outcomes.  The target enrollment is 238. The study is expected to be open for enrollment in September 2008.