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Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00122980 |
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).
Condition | Intervention | Phase |
---|---|---|
Hemochromatosis Cerebrovascular Accident Anemia, Sickle Cell Hematologic Diseases |
Procedure: Red Cell Transfusions Procedure: Iron Chelation Drug: Hydroxyurea Procedure: Phlebotomy |
Phase III |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Open Label, Parallel Assignment, Efficacy Study |
Official Title: | Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) |
Estimated Enrollment: | 130 |
Study Start Date: | August 2005 |
Estimated Study Completion Date: | July 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1: Active Comparator
Hydroxyurea and phlebotomy
|
Drug: Hydroxyurea
Hydroxyurea
Procedure: Phlebotomy
Phlebotomy
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2: Active Comparator
Transfusion and chelation
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Procedure: Red Cell Transfusions
Red Blood Cell Transfusions
Procedure: Iron Chelation
Iron Chelation Therapy
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BACKGROUND:
Stroke occurs in 10% of children with SCA and has a very high risk of recurrence without therapy. Affected children receive chronic erythrocyte transfusions to prevent a secondary stroke, which are effective but have limited long-term utility due to transmission of infectious agents, erythrocyte alloantibody and autoantibody formation, and iron overload. Transfusion acquired iron overload can cause chronic organ damage with hepatic fibrosis and cirrhosis, poor growth and development, cardiac arrhythmias, and early sudden death in young patients with SCA and stroke. An alternative to transfusions for secondary stroke prevention that also addresses the issue of transfusion acquired iron overload is clearly needed. Hydroxyurea can prevent acute vaso-occlusive events in SCA, but its utility for cerebrovascular disease and for the prevention of secondary stroke in SCA is not proven. Pilot data indicate hydroxyurea can prevent stroke recurrence in children with SCA; after transfusions are discontinued, serial phlebotomy reduces iron burden.
DESIGN NARRATIVE:
This is a Phase III randomized clinical trial for children with SCA. The hypothesis is that hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence rate and significantly reduce the hepatic iron burden. The primary aim 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. Additional aims include comparisons of growth and development, frequency of non-stroke neurological and other sickle-related events, and quality of life. The use of hydroxyurea for secondary stroke prevention, coupled with removal of excess iron by phlebotomy, would represent a significant improvement in the management of individuals with SCA and stroke. If hydroxyurea is effective for the prevention of secondary stroke, it may also be beneficial for other children with SCA and cerebrovascular disease, including those at risk for primary stroke.
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. The impetus for this trial is the fact that long-term transfusion and chelation therapy in children is difficult, is frequently unsuccessful, and is often complicated by severe symptomatic iron overload, particularly of the heart, lungs, and liver.
Ages Eligible for Study: | 5 Years to 18 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following:
Inability to take or tolerate daily oral hydroxyurea, due to any of the following:
Clinical and laboratory evidence of hypersplenism, due to any of the following:
Abnormal laboratory values at initial evaluation (temporary exclusion):
Contact: William Schultz, PA-C | 901-595-2923 | william.schultz@stjude.org |
Contact: Russell E. Ware, MD, PhD | 901-595-4238 | russell.ware@stjude.org |
Principal Investigator: | Russell E. Ware, MD, PhD | St. Jude Children's Research Hospital |
Principal Investigator: | Ronald W. Helms, PhD | Rho Incorporated |
Responsible Party: | St. Jude Children's Research Hospital ( Russell E. Ware, MD, PhD ) |
Study ID Numbers: | 227, U01 HL78787 |
Study First Received: | July 20, 2005 |
Last Updated: | August 7, 2008 |
ClinicalTrials.gov Identifier: | NCT00122980 |
Health Authority: | United States: Data Safety Monitoring Board, NHLBI; United States: Food and Drug Administration |
Blood Diseases |
Cerebral Infarction Hydroxyurea Hemochromatosis, type 3 Iron Metabolism Disorders Brain Diseases Cerebrovascular Disorders Metabolism, Inborn Errors Brain Ischemia Hemoglobinopathy Anemia, Sickle Cell Metabolic Diseases Hematologic Diseases Stroke Anemia |
Vascular Diseases Anemia, Hemolytic Central Nervous System Diseases Ischemia Anemia, Hemolytic, Congenital Genetic Diseases, Inborn Hemoglobinopathies Hemochromatosis Iron Overload Brain Infarction Infarction Metabolic disorder Iron |
Antisickling Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Hematologic Agents Nervous System Diseases |
Enzyme Inhibitors Cardiovascular Diseases Metal Metabolism, Inborn Errors Nucleic Acid Synthesis Inhibitors Pharmacologic Actions |