Sickle Cell Disease
Conditions
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
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.
Interventions
DRUGaspirin
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.
Sponsors
University of Miami
Bayer
National Institute of Neurological Disorders and Stroke (NINDS)
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 7 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events | 12 months | Occurrence of individual serious adverse events and relationship to aspirin |
| Number of Adverse Events | 12 months | Occurrence of individual adverse events and relationship to aspirin |
Secondary
| Measure | Time frame |
|---|---|
| # 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 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin 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. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Aspirin |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 11 |
| serious Total, serious adverse events | 8 / 11 |
Outcome results
Primary
Number of Adverse Events
Occurrence of individual adverse events and relationship to aspirin
Time frame: 12 months
Population: Intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aspirin | Number of Adverse Events | Unlikely | 3 events |
| Aspirin | Number of Adverse Events | Possible | 5 events |
| Aspirin | Number of Adverse Events | Probable | 1 events |
| Aspirin | Number of Adverse Events | Definite | 2 events |
| Aspirin | Number of Adverse Events | No relationship | 8 events |
Primary
Number of Serious Adverse Events
Occurrence of individual serious adverse events and relationship to aspirin
Time frame: 12 months
Population: Intention to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aspirin | Number of Serious Adverse Events | No relationship | 6 events |
| Aspirin | Number of Serious Adverse Events | Unlikely | 9 events |
| Aspirin | Number of Serious Adverse Events | Possible | 0 events |
| Aspirin | Number of Serious Adverse Events | Probable | 0 events |
| Aspirin | Number of Serious Adverse Events | Definite | 0 events |
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
Time frame: 12 months