START: Aspirin Prophylaxis in Sickle Cell Disease

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT00178464
• Collaborator: University of Miami (Other), Bayer (Industry), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 11
• Arm: 1
• Duration (Months): 56

Study Details

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
• 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: Mar 1, 2005
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Nov 1, 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 [12 months]

   Occurrence of individual serious adverse events and relationship to aspirin

2. Number of Adverse Events [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 [12 months]

Eligibility Criteria

Criteria

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

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

Locations

No locations specified.

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Rochester
• ClinicalTrials.gov Identifier: NCT00178464
• Other Study ID Numbers: 09661; 5R01NS045948-03
• First Posted: Sep 15, 2005
• Last Update Posted: Nov 6, 2017
• Last Verified: Oct 1, 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; Aspirin

Study Results

Participant Flow

Arm/Group Title	Aspirin
Arm/Group Description	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.
Period Title: Overall Study
STARTED	11
COMPLETED	9
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Aspirin
Arm/Group Description	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.
Overall Participants	11
Age (Count of Participants)
<=18 years	11 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 63.6%
Male	4 36.4%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Number of Serious Adverse Events
Description	Occurrence of individual serious adverse events and relationship to aspirin
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Aspirin
Arm/Group Description	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.
Measure Participants	8
No relationship	6
Unlikely	9
Possible	0
Probable	0
Definite	0

2. Secondary Outcome

Title	# 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Primary Outcome

Title	Number of Adverse Events
Description	Occurrence of individual adverse events and relationship to aspirin
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Aspirin
Arm/Group Description	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.
Measure Participants	8
No relationship	8
Unlikely	3
Possible	5
Probable	1
Definite	2

Adverse Events

Arm/Group Title	Aspirin
Arm/Group Description	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.
All Cause Mortality
	Aspirin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aspirin
	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)
Blood and lymphatic system disorders
Severe Anemia resulting in hospitalization	1/11 (9.1%)	1
Splenic Sequestration	1/11 (9.1%)	1
General disorders
Fever resulting in Hospitalization	6/11 (54.5%)	7
Musculoskeletal and connective tissue disorders
Vasoocclusive Crisis Pain resulting in hospitalization	2/11 (18.2%)	6
Fracture resulting in hospitalization	1/11 (9.1%)	1
Nervous system disorders
Abnormal MRA resulting in withdrawal from study.	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia resulting in hospitalization	1/11 (9.1%)	1
Asthma resulting in hospitalization	1/11 (9.1%)	1
Acute Chest Syndrome resulting in hospitalization.	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Aspirin
	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)
Blood and lymphatic system disorders
Bleeding per rectum	1/11 (9.1%)	3
Epistaxis	2/11 (18.2%)	3
Ear and labyrinth disorders
Otitis Media	1/11 (9.1%)	1
Gastrointestinal disorders
Epigastric pain	1/11 (9.1%)	1
Tarry stool	1/11 (9.1%)	1
General disorders
Fever	2/11 (18.2%)	2
Pain	3/11 (27.3%)	3
Allergic reaction	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/11 (9.1%)	1
Upper Respiratory Infection	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Scabies	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.