Stroke prevention trial in sickle cell anemia

Area of Science:

• Pediatric Neurology
• Hematology
• Vascular Medicine

Background:

• Stroke is a significant cause of morbidity in children with Sickle Cell Disease (Hb SS).
• While chronic blood transfusions reduce stroke recurrence, primary prevention of a first stroke is essential to prevent irreversible brain injury.
• Transcranial Doppler (TCD) ultrasound identifies children at high risk for stroke based on blood flow velocity.

Purpose of the Study:

• To evaluate the effectiveness of periodic blood transfusions in reducing the risk of first-time stroke in children with Hb SS.
• To determine if reducing sickle hemoglobin levels to ≤30% via transfusion can decrease stroke incidence by at least 70% compared to standard care.
• To assess the impact of transfusions on asymptomatic brain lesions detected by MRI/MRA.

Main Methods:

• The multi-center Stroke Prevention Trial in Sickle Cell Anemia (STOP) randomized children with Hb SS to receive either blood transfusions or standard care.
• Screening involved standardized Transcranial Doppler (TCD) ultrasound and Magnetic Resonance Imaging/Angiography (MRI/MRA) protocols.
• Primary endpoints included clinically evident cerebral infarction or intracranial hemorrhage, with blinded adjudication.

Main Results:

• A time-averaged mean velocity of ≥200 cm/sec on TCD is associated with a 46% risk of cerebral infarction over 39 months.
• The study is powered to detect a 70% reduction in the primary endpoint with 90% power.
• Standardized TCD and MRI/MRA protocols with blinded interpretation and endpoint adjudication are key trial features.

Conclusions:

• This trial aims to establish whether blood transfusions are effective in the primary prevention of stroke in children with Hb SS.
• Findings will inform future research into cerebrovascular disease and optimize treatment strategies for Hb SS.
• The study's design addresses the critical need for primary stroke prevention in this vulnerable pediatric population.