Design of the silent cerebral infarct transfusion (SIT) trial.
BACKGROUND
Silent cerebral infarct (SCI) is the most common cause of serious neurological disease in sickle cell anemia (SCA), affecting approximately 22% of children. The goal of this trial is to determine whether blood transfusion therapy will reduce further neurological morbidity in children with SCI, and if so, the magnitude of this benefit.


METHODS
The Silent Cerebral Infarct Transfusion (SIT) Trial includes 29 clinical sites and 3 subsites, a Clinical Coordinating Center, and a Statistical and Data Coordinating Center, to test the following hypothesis: prophylactic blood transfusion therapy in children with SCI will result in at least an 86% reduction in the rate of subsequent overt strokes or new or progressive cerebral infarcts as defined by magnetic resonance imaging (MRI) of the brain. The intervention is blood transfusion versus observation. Two hundred and four participants (102 in each treatment assignment) will ensure 85% power to detect the effect necessary to recommend transfusion therapy (86% reduction), after accounting for 10% drop out and 19% crossover rates. MRI examination of the brain is done at screening, immediately before randomization and study exit. Each randomly assigned participant receives a cognitive test battery at study entry, 12-18 months later, and study exit and an annual neurological examination. Blood is obtained from all screened participants for a biologic repository containing serum and a renewable source of DNA.


CONCLUSIONS
The SIT Trial could lead to a change in standard care practices for children affected with SCA and SCI, with a consequent reduction in neurological morbidity.
Casella
James F
JF
Pediatric Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. jcasella@jhmi.edu
King
Allison A
AA
Barton
Bruce
B
White
Desiree A
DA
Noetzel
Michael J
MJ
Ichord
Rebecca N
RN
Terrill
Cindy
C
Hirtz
Deborah
D
McKinstry
Robert C
RC
Strouse
John J
JJ
Howard
Thomas H
TH
Coates
Thomas D
TD
Minniti
Caterina P
CP
Campbell
Andrew D
AD
Vendt
Bruce A
BA
Lehmann
Harold
H
Debaun
Michael R
MR
D000755:Anemia, Sickle Cell / Q000150:complications*; D001803:Blood Transfusion; D002544:Cerebral Infarction / Q000150:complications* / Q000517:prevention & control / Q000628:therapy*; D002648:Child; D006801:Humans; D008279:Magnetic Resonance Imaging; D012107:Research Design; D020521:Stroke / Q000150:complications / Q000517:prevention & control / Q000628:therapy