Aspirin Prophylaxis in Sickle Cell Disease "START"

Completed

Phase 1 Results

Trial Description

Neurologic complications secondary to cerebrovascular damage are prevalent in children with sickle cell disease. These patients experience both clinically overt cerebrovascular accidents and "silent infarctions" demonstrated by magnetic resonance imaging (MRI). They are also at risk for neurocognitive abnormalities.We hypothesize that daily, low-dose aspirin therapy will safely diminish the incidence and progression of cognitive deficits as well as the predisposition to overt and silent stroke in children with homozygous sickle cell disease (Hgb SS) or hemoglobin S Beta Zero Thalassemia (Hgb SB-0 Thal). In order to optimize the design of a future trial to test this hypothesis, we propose a pilot study to test the safety and tolerability of aspirin in young children with sickle cell disease.

Detailed Description

The trial's primary objective is to evaluate the safety and tolerability of daily low-dose aspirin in children with sickle cell disease. The secondary objectives are to assess (1) The feasibility of recruiting children with Hgb SS and Hgb S Beta-0 Thalassemia to an aspirin trial, (2) The level of compliance with aspirin administration in the proposed patient population, (3) The most useful assessments in a battery of age-appropriate neurocognitive tests, (4) The feasibility of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) studies and the utility of classification systems for use in group comparisons, (5) Preliminary data regarding trends in transcranial Doppler (TCD) ultrasound velocities over time and the validity of using trends for group comparisons, (6) Preliminary data regarding the effect of aspirin therapy on the incidence of cognitive deficit, imaging changes, overt stroke, painful crises, and acute chest syndrome. Subjects will include children between the ages of 2 and 7.99 years with documented Hgb SS or Hgb S Beta-0 Thalassemia who are followed at Golisano Children's Hospital at Strong and the University of Miami. All subjects will receive daily aspirin (about 2.5 - 5.1 mg/kg daily). Subjects will receive therapy for 12 months. There will be careful laboratory and clinical monitoring every 3-6 months and more frequently if needed. Pre and post treatment clinical complications, neurocognitive testing, MRI, MRA, and TCD studies will be assessed.

Conditions

Interventions

  • Aspirin Drug
    Other Names: Aspirin at bedtime
    Intervention Desc: 81 mg flavored chewable tablets. Subjects between the ages of 2.0 and 4.99 years will receive half of an 81 mg aspirin tablet each day. Those older than 5.0 years will receive a daily 81 mg aspirin tablet. The subject will receive the study drug for a period of 12 months.
    ARM 1: Kind: Experimental
    Label: Aspirin
    Description: One-arm study

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Single Group Assignment

Patient Involvement

Subjects will be randomized to one of two treatment groups, daily aspirin (about 2.5 - 5.1 mg/kg daily) or placebo. Subjects will receive therapy for 18 months. There will be careful laboratory and clinical monitoring every 3 months and more frequently if needed. Group comparisons regarding pre and post treatment clinical complications, neurocognitive testing, MRI, MRA, and TCD studies will be made.

Outcomes

Type Measure Time Frame Safety Issue
Primary Ability to complete the trial on the originally assigned dosage of study medication with or without dosage modification or suspension; occurrence of individual adverse events, intracranial hemorrhage &/or Reyes syndrome.
Secondary Number of subjects recruited over time, screening failures, withdrawl rates; compliance (pill counts & labs); changes in performance on neurocognitive tests; changes in MRI/MRA; changes in TCD; incidences of stroke, acute chest crises, and pain crises.
Primary Ability to complete the trial on the originally assigned dosage of study medication with or without dosage modification or suspension; Occurrence of individual adverse events, intracranial hemorrhage &/or Reyes syndrome 12 months Yes
Secondary # of subjects recruited over time, screening failures, withdrawal rates;Compliance (pill counts & labs);Changes in performance on neurocognitive tests; Changes in MRI/MRA; Changes in TCD;Incidences of stroke, acute chest crises, and pain crises 12 months Yes
Primary Number of Serious Adverse Events 12 months Yes
Primary Number of Adverse Events 12 months Yes

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