Clinical trial NCT00178464: Aspirin Prophylaxis in Sickle Cell Disease
Official title: Aspirin Prophylaxis in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
hemoglobin SS disease
hemoglobin S Beta-0 Thalassemia
silent infarction in sickle cell disease
overt stroke in sickle cell disease
aspirin
transcranial Doppler ultrasound
neurocognitive testing
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: University of Miami
name: Bayer
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2005-09-15
Enrollment: 11
Sex: ALL
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

* 1. Children ages 2 - 7.99 years with a diagnosis of Hb SS or Hb Sß0 thalassemia, documented by hemoglobin electrophoresis and a complete blood count (CBC). 2. Influenza vaccination during the previous year or intended before the upcoming flu season. 3. Evidence of past infection with, or immunization against, varicella. 4. Negative pregnancy tests in girls of childbearing potential. 5. Informed consent signed by the parent or legal guardian.

Exclusion Criteria:

* 1. Prior history of overt stroke or cerebral hemorrhage. 2. Known history of allergic reaction to aspirin. 3. History of Reye's syndrome 4. Diagnosis of G-6-PD deficiency or von Willebrand's disease 5. Prolongation of the bleeding time or abnormal closure time, prothrombin time (PT), or partial thromboplastin time (PTT). 6. Active gastrointestinal (GI) bleeding or a history of GI bleeding. 7. Hepatic disease (AST or ALT \>2x upper limit of normal, Direct bilirubin \> 1.5 mg/dL) or renal disease (creatinine \>2x upper limit of normal or 2 mg/dl, whichever is smaller). The exclusion criteria laboratory study ranges have been specified as greater than 2 times the upper limit of normal. 8. Hypertension (BP \>95% for age and height). 9. Current treatment with chronic transfusion therapy. 10. Evidence of hemorrhage on MRI. 11. A mean TCD velocity \> 200 cm/sec. in the middle cerebral artery (MCA) or internal carotid artery (ICA). 12. Evidence of Moyamoya syndrome on MRA. 13. Evidence of pregnancy. 14. Evidence of an inability to comply with testing procedures. 15. Inability to provide informed consent.

Primary outcomes:
measure: Number of Serious Adverse Events
timeFrame: 12 months
measure: Number of Adverse Events
timeFrame: 12 months
Secondary outcomes:
measure: # 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
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Rochester
name: Norma B. Lerner, MD
role: PRINCIPAL_INVESTIGATOR
References: