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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Disease	Drug: aspirin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Aspirin Prophylaxis in Sickle Cell Disease
• Study Start Date: March 2005
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: November 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Aspirin; One-arm study	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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. # 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 ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 7 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Sponsors and Collaborators

University of Rochester

University of Miami

Bayer

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

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

More Information

• Responsible Party: University of Rochester
• ClinicalTrials.gov Identifier: NCT00178464
• Other Study ID Numbers: 09661; 5R01NS045948-03 ( U.S. NIH Grant/Contract )
• First Posted: September 15, 2005
• Results First Posted: January 4, 2012
• Last Update Posted: November 6, 2017
• Last Verified: October 2017

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

Keywords provided by University of Rochester:

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

Additional relevant MeSH terms:

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics