Stroke prevention in sickle cell disease (stop): Final results

The STOP Trial was a randomized controlled trial to determine if chronic blood transfusion reduced first time stroke in children with Hb SS. Over 2,000 patients were screened with transcranial Doppier (TCD). Sixty-three were randomized to transfusion (goal: to reduce HbS to < 30%) and 67 to standard care between January 1995 and October 1996. The trial was halted in September 1997, after demonstration of a large beneficial treatment effect. Patients were offered transfusion and follow-up through the end of the study in June 2000. The status of 129 were known at close-out. Two died of causes unrelated to stroke. Fourteen patients (excluding one with stroke at randomization) not receiving transfusion had stroke while a total of 3 children had stroke while on transfusion for an average of 28 months. One other had a recurrent stroke despite being on transfusion. Forty-eight of the original 63 randomized to transfusion continued, one crossover restarted chronic transfusion on a clinical basis, and 43 of these 49 were on treatment at study closeout. Of the 67 randomized to standard care, 42 were being transfused; 13 for stroke, one for leg ulcers, and 28 who chose treatment to prevent stroke as of 06/30/00. For the 104 enrolled in the follow-up phase without stroke, TCD and MRI findings at last testing (mid-late 1999) were: 19 (18.27%) abnormal, 34 (32.69%) conditional, 41 (39.42%) normal and 10 (9.62%) inadequate. Close-out MRI showed that 46 (46.46%) had silent infarcts vs. 37% at baseline. There were 10 patients (out of 39 with an évaluable final MRA) with moderate or severe lesions on MRA. A total of 4,536 transfusions were delivered in this study (on and off protocol). No HIV or new Hepatitis C infections were detected. A total of 72 patients received chelation during the study. The STOP Trial demonstrated that: TCD can predict stroke, and the risk is sustained for at least 2-3 years after abnormal exam: transfusion lowers risk of stroke, but is not accepted by all patients, and is associated with complications, especially iron overload. A second trial will examine the duration of transfusion needed to achieve primary stroke prevention in this setting.