SWiTCH
Stroke With Transfusions Changing to Hydroxyurea
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Status:
This study is ongoing, but not recruiting participants.
Purpose:
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).
Interventions:
Chelation therapy
Chelation therapy is the administration of chelating agents to remove heavy metals from the body.
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Hydroxyurea
Hydroxyurea treats sickle cell anemia by changing red blood cells so that they are less likely to bend in an abnormal shape.
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Phlebotomy
Removal of blood for treatment reasons.
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Transfusion
Blood exchange for stroke prophylaxis in sickle cell anemia
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Location(s):
United States
Year Started:
2005
Design:
Interventional, Randomized, Efficacy Study, Parallel Assignment, Open Label, Prevention.
Inclusion Criteria
Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 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:
Multiple RBC alloantibodies making cross-matching difficult or impossible
RBC autoantibodies making cross-matching difficult or impossible
Religious objection to transfusions that preclude their chronic use
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:
Known allergy to hydroxyurea therapy
HIV infection
Cancer
Pregnant or breastfeeding
Previous stem cell transplant or other myelosuppressive therapy
Clinical and laboratory evidence of hypersplenism, due to any of the following:
Palpable splenomegaly greater than 5 cm below the left costal margin and
Transfusion requirement greater than 250 mL/kg in the 12 months prior to study entry
Abnormal laboratory values at initial evaluation (temporary exclusion):
Pre-transfusion hemoglobin concentration less than 7.0 gm/dL
White blood cell (WBC) count less than 3.0 x 109/L
Absolute neutrophil count (ANC) less than 1.5 x 109/L
Platelet count less than 100 x 109/L
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
Patient Involvement:
The trial includes approximately 130 children (5.0-18.9 years of age with 65 subjects per treatment arm) with SCA who have had symptomatic cerebral infarctions and have been treated with red cell transfusions for at least 18 months. After completing baseline screening studies, half the participants will be switched to a therapeutic program of hydroxyurea and phlebotomy. Half of the participants will remain on transfusion and chelation. The composite primary endpoint in this study is to compare two modalities of treatment for the prevention of secondary stroke and management of iron overload.
Primary Outcome:
Secondary stroke
Secondary Outcome:
Comparisons of growth and development; frequency of non-stroke neurological and other sickle-related events; quality of life; neurocognitive decline; transfusion-, chelation-, hydroxyurea-, phlebotomy- and liver biopsy-related complications.
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Source of Information:
ClinicalTrials.gov
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Web Links and Publications:
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This information last updated on: 6/16/2010
Reviewed on: 06/08/2010.
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