STROKE PREVENTION TRIAL IN SICKLE-CELL-ANEMIA

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Preve ntion of first stroke, however, would be preferable because even one s troke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subseq uent stroke risk. By combining TCD screening and a potentially effecti ve treatment, first stroke may be prevented. The Stroke Prevention Tri al in Sickle Cell Anemia (STOP) is the first stroke prevention trial i n Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickl e hemoglobin to 30% or less with periodic blood transfusions will redu ce first-time stroke by at least 70% compared to standard care. Primar y endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiograph y (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoint s will be asymptomatic brain lesions detected by MRI in brain areas no t involved in primary endpoints. The design calls for a 6-month start- up interval, 18 months of TCD screening and randomization, and observa tion for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and b linded adjudication of endpoints. The sample size (60 per treatment gr oup) is based on prospective data relating TCD velocity to risk of str oke. A time-averaged mean velocity of greater than or equal to 200 cm/ sec is associated with a 46% risk of cerebral infarction over 39 month s. The sample size is sufficient to detect 70% reduction in the primar y endpoint at 90% power. This trial will determine if transfusion is e ffective in the primary prevention of stroke. Secondary aims may furth er the understanding of the effects of transfusion on the brain and gu ide future research into cerebrovascular disease in Hb SS. (C) Elsevie r Science Inc. 1998.