Aspirin Prophylaxis in Sickle Cell Disease (START)

• ClinicalTrials.gov Identifier: NCT00178464
• Recruitment Status: Completed
• First Posted: September 15, 2005
• Results First Posted: January 4, 2012
• Last Update Posted: November 6, 2017
• Sponsor: University of Rochester
• Collaborators: University of Miami; Bayer; National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): University of Rochester

Tracking Information

• First Submitted Date: September 13, 2005
• First Posted Date: September 15, 2005
• Results First Submitted Date: August 9, 2011
• Results First Posted Date: January 4, 2012
• Last Update Posted Date: November 6, 2017
• Study Start Date: March 2005
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2011)

• Number of Serious Adverse Events [ Time Frame: 12 months ]
  Occurrence of individual serious adverse events and relationship to aspirin
• Number of Adverse Events [ Time Frame: 12 months ]
  Occurrence of individual adverse events and relationship to aspirin

• Original Primary Outcome Measures (submitted: September 13, 2005): 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
• Current Secondary Outcome Measures (submitted: November 29, 2011): # 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 [ Time Frame: 12 months ]
• Original Secondary Outcome Measures (submitted: September 13, 2005): # 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
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Aspirin Prophylaxis in Sickle Cell Disease
• Official Title: Aspirin Prophylaxis in Sickle Cell Disease
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

Drug: aspirin

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.

Other Names:

• Acetylsalicyclic Acid
• ASA

Study Arms

Experimental: Aspirin

One-arm study

Intervention: Drug: aspirin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2011): 11
• Original Enrollment (submitted: September 13, 2005): 60
• Actual Study Completion Date: November 2009
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT00178464
• Other Study ID Numbers: 09661; 5R01NS045948-03 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Rochester
• Original Responsible Party: Not Provided
• Current Study Sponsor: University of Rochester
• Original Study Sponsor: Same as current

Collaborators

• University of Miami
• Bayer
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Norma B. Lerner, MD; University of Rochester

• PRS Account: University of Rochester
• Verification Date: October 2017