title: Stroke With Transfusions Changing to Hydroxyurea (SWiTCH): a phase III randomized clinical trial for treatment of children with sickle cell anemia, stroke, and iron overload.
abstract: BACKGROUND
  Stroke occurs in 5-10% of children with sickle cell anemia (SCA) and has a high (>50%) risk of recurrence without therapy. Chronic monthly erythrocyte transfusions effectively prevent recurrent stroke, but their long-term use is limited by serious side effects, including iron overload. An alternative to transfusion for secondary stroke prevention in SCA is needed, especially one that also improves the management of iron overload.
  
  
  METHODS
  Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) is an NHLBI-sponsored Phase III multicenter randomized controlled clinical trial for children with SCA, stroke, and iron overload (NCT00122980). The primary goal of SWiTCH is to compare 30 months of alternative therapy (hydroxyurea and phlebotomy) with standard therapy (transfusions and chelation) for the prevention of secondary stroke and reduction of transfusional iron overload.
  
  
  CONCLUSIONS
  SWiTCH has several distinctive study features including novel methodological and design components: (1) composite primary endpoint including both stroke recurrence rate and iron burden; (2) non-inferiority design with an "acceptable" increased stroke risk; (3) transfusion goals based on current academic community practices; (4) special oversight for the enrollment and randomization process; (5) overlap treatment period within the alternative treatment arm; (6) masking of the overall trial Principal Investigator to treatment results; (7) inclusive independent stroke adjudication process for all suspected new neurological events; and (8) periodic therapeutic phlebotomy program to alleviate iron overload.
  
  
  CONCLUSIONS
  Investigation of alternative treatments in SWiTCH could lead to changes in the management of cerebrovascular disease for selected patients with SCA, stroke, and iron overload.
authors.affiliation: St. Jude Children's Research Hospital, Baylor College of Medicine, Houston, TX 77030, USA. reware@bcm.edu
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: William H
authors.initials: WH
authors.lastname: Schultz
authors.forename: Nancy
authors.initials: N
authors.lastname: Yovetich
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mortier
authors.forename: Ofelia
authors.initials: O
authors.lastname: Alvarez
authors.forename: Lee
authors.initials: L
authors.lastname: Hilliard
authors.forename: Rathi V
authors.initials: RV
authors.lastname: Iyer
authors.forename: Scott T
authors.initials: ST
authors.lastname: Miller
authors.forename: Zora R
authors.initials: ZR
authors.lastname: Rogers
authors.forename: J Paul
authors.initials: JP
authors.lastname: Scott
authors.forename: Myron
authors.initials: M
authors.lastname: Waclawiw
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Helms
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000628:therapy*; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D019190:Iron Overload / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D055815:Young Adult
chemical_list: D006918:Hydroxyurea