Cerebrovascular Accident Clinical Trial
Official title:
Stroke With Transfusions Changing to Hydroxyurea
The purpose of this study is to compare standard therapy (transfusions and chelation) with alternative therapy (hydroxyurea and phlebotomy) for the prevention of secondary stroke and management of iron overload in children with sickle cell anemia (SCA).
Status | Terminated |
Enrollment | 134 |
Est. completion date | December 2010 |
Est. primary completion date | June 2010 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 5 Years to 18 Years |
Eligibility |
Inclusion Criteria: - Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSĂ0 thalassemia, HbSOArab) - Age range of 5.0-18.9 years, inclusive, at the time of study entry - Initial (primary) completed overt clinical stroke after the age of one year (12 months) with documented infarction on brain computed tomography (CT) or magnetic resonance imaging (MRI) - At least 18 months of chronic monthly erythrocyte transfusions since primary stroke - Transfusional iron overload, defined as a previously documented liver iron concentration (LIC) greater than or equal to 5.0 mg Fe per gram of dry weight liver or serum ferritin greater than or equal to 500 ng/mL on two independent measurements - Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) in the 6 months prior to study entry - Parent or guardian willing and able to provide informed consent with verbal or written assent from the child (less than 18 years of age) or subject willing and able to provide informed consent (older than 18 years of age) - Ability to comply with study-related treatments, evaluations, and follow-up Exclusion Criteria: - Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following: 1. Multiple RBC alloantibodies making cross-matching difficult or impossible 2. RBC autoantibodies making cross-matching difficult or impossible 3. Religious objection to transfusions that preclude their chronic use 4. Non-compliance with transfusions in the 6 months prior to study entry (temporary exclusion) - Inability to take or tolerate daily oral hydroxyurea, due to any of the following: 1. Known allergy to hydroxyurea therapy 2. HIV infection 3. Cancer 4. Pregnant or breastfeeding 5. Previous stem cell transplant or other myelosuppressive therapy - Clinical and laboratory evidence of hypersplenism, due to any of the following: 1. Palpable splenomegaly greater than 5 cm below the left costal margin and 2. Transfusion requirement greater than 250 mL/kg in the 12 months prior to study entry - Abnormal laboratory values at initial evaluation (temporary exclusion): 1. Pre-transfusion hemoglobin concentration less than 7.0 gm/dL 2. White blood cell (WBC) count less than 3.0 x 109/L 3. Absolute neutrophil count (ANC) less than 1.5 x 109/L 4. Platelet count less than 100 x 109/L 5. Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL - Current participation in other therapeutic clinical trials - Current use of other therapeutic agents for SCA (e.g., arginine, decitabine, magnesium) - Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the study physician makes study participation ill-advised - Inability or unwillingness to complete required screening studies, including blood tests, brain MRI/magnetic resonance angiography (MRA), and liver biopsy - A sibling enrolled in SWiTCH |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
United States | Children's Healthcare of Atlanta at Egleston | Atlanta | Georgia |
United States | Children's Healthcare of Atlanta at Grady | Atlanta | Georgia |
United States | Children's Healthcare of Atlanta at Scottish Rite | Atlanta | Georgia |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Boston Children's Hospital | Boston | Massachusetts |
United States | Montefiore Medical Center | Bronx | New York |
United States | State University of New York/Downstate Medical Center | Brooklyn | New York |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Children's Memorial Hospital | Chicago | Illinois |
United States | Cincinnati Children's Hospital | Cincinnati | Ohio |
United States | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas |
United States | Wayne State University, Children's Hospital of Michigan | Detroit | Michigan |
United States | East Carolina University | Greenville | North Carolina |
United States | Baylor College of Medicine | Houston | Texas |
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Nemours Children's Clinic | Jacksonville | Florida |
United States | The Children's Mercy Hospital | Kansas City | Missouri |
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
United States | University of Miami, Jackson Memorial Hospital | Miami | Florida |
United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
United States | Schneider Children's Hospital | New Hyde Park | New York |
United States | Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian | New York | New York |
United States | Eastern Virginia Medical School | Norfolk | Virginia |
United States | Nemours Children's Clinic | Orlando | Florida |
United States | St. Joseph's Children's Hospital | Paterson | New Jersey |
United States | The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
United States | Children's National Medical Center | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
St. Jude Children's Research Hospital | National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Occurrence of an Adjudicated Secondary Stroke During the 30-month Treatment Period | Secondary stroke is the first component of the composite primary endpoint and considers the number of participants with recurrent secondary stroke events during 30 months of treatment. Stroke was defined as any clinical event with brain injury due to vascular disease. All neurological events underwent formal stroke adjudication. | Because the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 30 Months) | Yes |
Primary | Liver Iron Content (LIC) Change-from-baseline | LIC change-from-baseline is the second component of the composite primary endpoint. LIC was measured by quantitative liver biopsy at baseline and at 30 months or exit from the study.LIC values were transformed into Log10 values prior to computing the change from baseline. | Because the study was terminated early, time frame is from beginning of treatment until end of treatment (up to 30 Months) | No |
Secondary | Pediatric Quality of Life (PedsQL) - Parent Report (Change From Baseline) | The PedsQL(TM) Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. It has a Likert 5-points scale (never to almost always) which were transformed to a 0 to 100 scale based on the PedsQL scoring algorithms, higher scores indicating better quality of life characteristics. | Baseline, mid-point (week 64), and study exit after up to 30-month treatment period (due to study termination) | No |
Secondary | Pediatric Quality of Life (PedsQL) - Child Report (Change From Baseline) | The PedsQLTM Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. It has a Likert 5-points scale (never to almost always) which were transformed to a 0 to 100 scale based on the PedsQL scoring algorithms, higher scores indicating better quality of life characteristics. | Baseline, midpoint (week 64), and study exit (up to 30 months of treatment) | No |
Secondary | Barthel Index (Change From Baseline) | The Barthel Index is a measure of activities of daily living (ADL) and assesses the degree of disability in a particular participant. The index records indicators of independence in terms of the disability caused by impairments, such as those that may be sequelae of stroke. The index was used as a record of what the participant did, not as a record of what the participant could do. Barthel scores range from 0 to 100, with higher scores indicating greater independence in daily living activities (caring for oneself). | Baseline and study exit after up to 30-month treatment period (due to study termination) | No |
Secondary | Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)-Excluding Verbal | This test is designed to assess both broad and narrow cognitive abilities in children age 4 years and above as well as to measure major aspects of academic achievement in persons aged 2-90 years. Scaled scores range from 0-100. Higher scores mean better abilities/achievements. | Baseline and study exit after up to 30-month treatment period (due to study termination) | No |
Secondary | Woodcock-Johnson Test of Cognitive Abilities (WJ-C) and Achievement (WJ-III) (Change From Baseline)- Verbal Ability | This test is designed to assess both broad and narrow cognitive abilities in children age 4 years and above as well as to measure major aspects of academic achievement in persons aged 2-90 years. Higher scores mean better abilities/achievements. Scaled scores range from 0-100. | Baseline and study exit after up to 30-month treatment period (due to study termination) | No |
Secondary | Growth and Development - Height (Change From Baseline to Endpoint) | Baseline to end of study participation (up to 136 weeks) | No | |
Secondary | Growth and Development - Weight (Change From Baseline to Endpoint) | baseline to end of study participation (up to 136 weeks) | No |
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