Stroke Prevention in Sickle Cell Anemia (STOP 1)
Condition: Anemia, Sickle Cell; Cerebral Embolism and Thrombosis; Cerebrovascular Disorders; Hematologic Diseases; Hemoglobinopathies
MeSH terms: Cerebrovascular Disorders; Intracranial Embolism; Intracranial Embolism and Thrombosis; Thrombosis; Embolism; Embolism and Thrombosis; Anemia; Hematologic Diseases; Hemoglobinopathies; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 3

Summary: 
      To reduce episodes of first time stroke by 75 percent in children with sickle cell anemia by
      the administration of prophylactic transfusion therapy.
    

Detailed description: 
      BACKGROUND:

      Stroke, occurring in about 10 percent of pediatric patients with sickle cell disease, is one
      of the most devastating complications, with a high recurrence rate after the first episode.
      Several non-randomized studies have shown reduction in stroke recurrence when periodic blood
      transfusions are administered to maintain hemoglobin S under 30 percent. Periodic blood
      transfusions are associated with significant risks of iron overload and other complications
      and must be accompanied by parenteral iron chelation therapy. However, this has become a
      standard of care for prevention of recurrent stroke in SS children. Thus, a randomized trial
      of blood transfusion for secondary prevention would not be feasible because it would be
      considered unethical. Based on various studies, the recurrence rate is reduced from 46 to 67
      percent to approximately 7 percent on transfusion therapy. Because most stroke patients are
      left with some neurological deficit, and face a lifetime of disability, primary prevention
      would have a significant impact on the management of patients. However, because of
      complications of blood transfusions, the hypothesis should be proven by a randomized clinical
      trial.

      A primary prevention trial had not been possible because an acceptable means of detecting
      those children at risk of stroke was not available. The advent of TCD to identify arterial
      abnormalities for the prediction of stroke has provided a means of detection. TCD
      abnormalities have a high specificity (100 percent) and high sensitivity (90 percent) for
      detecting angiographically proven narrowing of arterial diameter. Thus, TCD examination of
      the basal cerebral arteries is predictive of who will develop a stroke.

      DESIGN NARRATIVE:

      Randomized, Phase III, multicenter. Approximately 3,000 children from 12 clinics were
      screened with transcranial Doppler (TCD). A total of 130 were randomized to receive either
      standard supportive care or periodic blood transfusions if they were found to be at high risk
      of stroke on the basis of elevated cerebral blood flow as measured by TCD screening tests.
      Primary endpoints included clinically evident symptoms of cerebral infarction with consistent
      findings on magnetic resonance imaging (MRI), and/or symptomatic intracranial hemorrhage.
      Secondary endpoints included asymptomatic brain lesions detected by MRI in brain areas not
      involved in primary endpoints. Hematologic characteristics of the high risk group were
      analyzed and serum and DNA samples frozen for future analysis. Recruitment ended in October
      1997 with the accrual of 130 subjects. The clinical phase ended in 1999.
    

Intervention name(s): blood transfusion
Intervention type(s): Procedure
Allocation: Randomized
Primary purpose: Prevention