Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial
Condition: Sickle Cell Anemia; Stroke
MeSH terms: Cerebral Infarction; Anemia, Sickle Cell; Infarction
Study type: Interventional
Phase: Phase 3

Summary: 
      The goal of this study is to determine the effectiveness of blood transfusion therapy for
      prevention of silent cerebral infarct (stroke) in children with sickle cell anemia.
    

Detailed description: 
      Silent cerebral infarct (stroke) is the most common cause of severe cognitive impairments and
      related neurological functions in children with sickle cell anemia. Currently there exists no
      systemic strategy to identify or treat children with silent strokes.

      The primary aim of this trial is to determine the effectiveness of blood transfusion therapy
      for the prevention of silent strokes in children with sickle cell anemia. This trial will
      also determine if blood transfusion therapy will prevent further cerebral injury and if the
      measured benefits of the therapy outweigh the risks associated with it.

      Participants in this multi-center trial will be randomly assigned to one of 2 groups-the
      blood transfusion group or the observation group. Those in the blood transfusion group will
      receive at least monthly blood transfusion therapy. All participants will have history and
      physical examinations every 3 months, and magnetic resonance imaging (MRI) at the beginning
      of their entry into the study and at study exit.

      Advances in the understanding and treatment of silent strokes will likely lead to a decrease
      in the burden associated with cerebral injury in children with sickle cell anemia and change
      the standard care for these children.

      Statistical Analyses: The original statistical analysis plan suggested a simple difference in
      proportions between the proportion of individuals with an endpoint in the transfusion group
      and the proportion of individuals with an endpoint in the usual care group using a
      traditional chi squared test. The data should be analyzed according to an intent to treat
      principal. Because of various logistical concerns in SIT, some individuals were not imaged
      within the 36-month window (30-42 months). We propose using all available information by
      changing the primary analysis from a dichotomous (yes/no) endpoint to a traditional
      epidemiological endpoint of an incidence rate in the group randomized to transfusion to the
      incidence rate in the group randomized to usual care. We will compute the incidence ratio:

      (a/ta)/(b/tb)

      Where "a" is the number of endpoints in the transfusion group, "ta" is the sum of the
      individual times at risk of the individuals randomized to the transfusion group, "b" is the
      number of endpoints in the observation group and "tb" is the sum of the individual times at
      risk of the individuals randomized to the observation group.

      Since the standard statistical test for it being different than 1.0 involves the assumption
      of a Poisson distribution, we will compute an "exact" 95% confidence interval using a
      bootstrap with a large number of replications.
    

Intervention name(s): transfusion therapy
Intervention type(s): Procedure
Intervention description(s): Those in the blood transfusion group will receive at least monthly blood transfusion therapy.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: silent cerebral infarct; silent stroke; sickle cell anemia; stroke; transfusion therapy