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Clinical Trial
. 2012 Apr 26;119(17):3925-32.
doi: 10.1182/blood-2011-11-392340. Epub 2012 Feb 7.

Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)

Russell E Ware  1 , Ronald W Helms; SWiTCH Investigators
Collaborators, Affiliations
Clinical Trial

Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)

Russell E Ware et al. Blood. .

Abstract

Stroke is a devastating complication of sickle cell anemia (SCA) with high recurrence if untreated. Chronic transfusions reduce recurrent strokes but have associated morbidities including iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to alternative treatment (hydroxyurea/phlebotomy) for children with SCA, stroke, and iron overload. SWiTCH was a noninferiority trial with a composite primary end point, allowing an increased stroke risk but requiring superiority for removing iron. Subjects on standard treatment received monthly transfusions plus daily deferasirox iron chelation. Subjects on alternative treatment received hydroxyurea plus overlap transfusions during dose escalation to maximum tolerated dose (MTD), followed by monthly phlebotomy. Subjects on standard treatment (N = 66) maintained 30% sickle hemoglobin (HbS) and tolerated deferasirox at 28.2 ± 6.0 mg/kg/d. Subjects on alternative treatment (N = 67) initiated hydroxyurea and 60 (90%) reached MTD at 26.2 ± 4.9 mg/kg/d with 29.1% ± 6.7% fetal hemoglobin (HbF). Adjudication documented no strokes on transfusions/chelation but 7 (10%) on hydroxyurea/phlebotomy, still within the noninferiority stroke margin. The National Heart, Lung, and Blood Institute closed SWiTCH after interim analysis revealed equivalent liver iron content, indicating futility for the composite primary end point. Transfusions and chelation remain a better way to manage children with SCA, stroke, and iron overload.

Trial registration: ClinicalTrials.gov NCT00122980.

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Figures

Figure 1
Figure 1
Enrollment, randomization, and follow-up of the SWiTCH study patients.
Figure 2
Figure 2
Laboratory parameters based on intention-to-treat population. (A) Hemoglobin concentration; (B) MCV; (C) percentage of HbS; (D) percentage of HbF; (E) ARC; (F) WBC; (G) ANC; (H) ferritin. Complete blood counts and reticulocytes were obtained locally, while hemoglobin electrophoresis and serum ferritin were measured centrally. The standard treatment arm is indicated by dashes, while the alternative treatment arm is indicated by the solid line. Values are illustrated as medians with 25%-75% whisker plots. All parameters are significantly different (P < .001) between treatment groups except for panel A, which had no difference.
Figure 3
Figure 3
Event-free (Kaplan-Meier) plots of adjudicated neurologic events for the SWiTCH trial, by treatment group. The standard treatment arm is indicated by dashes, while the alternative treatment arm is indicated by the solid line. (A) Stroke with P < .05; (B) TIA with P = NS; (C) stroke, TIA, or death with P = NS.
See this image and copyright information in PMC

Comment in

  • To SWiTCH or not to SWiTCH?
    de Montalembert M. de Montalembert M. Blood. 2012 Apr 26;119(17):3870-1. doi: 10.1182/blood-2012-02-410951. Blood. 2012. PMID: 22538492

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