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

Russell E. Ware, William H. Schultz, Nancy Yovetich, Nicole A. Mortier, Ofelia A Alvarez, Lee Hilliard, Rathi V. Iyer, Scott T. Miller, Zora R. Rogers, J. Paul Scott, Myron Waclawiw, Ronald W. Helms

Research output: Contribution to journalArticle

44 Citations (Scopus)

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. Discussion: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1011-1017
Number of pages7
JournalPediatric Blood and Cancer
Volume57
Issue number6
DOIs
StatePublished - Dec 1 2011

Fingerprint

Phase III Clinical Trials
Iron Overload
Hydroxyurea
Sickle Cell Anemia
Randomized Controlled Trials
Stroke
Therapeutics
Phlebotomy
Secondary Prevention
Chelation Therapy
National Heart, Lung, and Blood Institute (U.S.)
Cerebrovascular Disorders
Recurrence
Erythrocyte Transfusion
Complementary Therapies
Random Allocation

Keywords

  • Hydroxyurea
  • Iron overload
  • Stroke

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

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. / Ware, Russell E.; Schultz, William H.; Yovetich, Nancy; Mortier, Nicole A.; Alvarez, Ofelia A; Hilliard, Lee; Iyer, Rathi V.; Miller, Scott T.; Rogers, Zora R.; Scott, J. Paul; Waclawiw, Myron; Helms, Ronald W.

In: Pediatric Blood and Cancer, Vol. 57, No. 6, 01.12.2011, p. 1011-1017.

Research output: Contribution to journalArticle

Ware, RE, Schultz, WH, Yovetich, N, Mortier, NA, Alvarez, OA, Hilliard, L, Iyer, RV, Miller, ST, Rogers, ZR, Scott, JP, Waclawiw, M & Helms, RW 2011, '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', Pediatric Blood and Cancer, vol. 57, no. 6, pp. 1011-1017. https://doi.org/10.1002/pbc.23145
Ware, Russell E. ; Schultz, William H. ; Yovetich, Nancy ; Mortier, Nicole A. ; Alvarez, Ofelia A ; Hilliard, Lee ; Iyer, Rathi V. ; Miller, Scott T. ; Rogers, Zora R. ; Scott, J. Paul ; Waclawiw, Myron ; Helms, Ronald W. / 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. In: Pediatric Blood and Cancer. 2011 ; Vol. 57, No. 6. pp. 1011-1017.
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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. Discussion: 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. Conclusion: 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.",
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AU - Ware, Russell E.

AU - Schultz, William H.

AU - Yovetich, Nancy

AU - Mortier, Nicole A.

AU - Alvarez, Ofelia A

AU - Hilliard, Lee

AU - Iyer, Rathi V.

AU - Miller, Scott T.

AU - Rogers, Zora R.

AU - Scott, J. Paul

AU - Waclawiw, Myron

AU - Helms, Ronald W.

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N2 - 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. Discussion: 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. Conclusion: 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.

AB - 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. Discussion: 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. Conclusion: 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.

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