Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea "TWiTCH"

Terminated

Phase 3 Results N/A

Trial Description

The primary goal of the Phase III TWiTCH trial is to compare 24 months of alternative therapy (hydroxyurea) to standard therapy (transfusions) for pediatric subjects with sickle cell anemia and abnormally high (≥200 cm/sec) Transcranial Doppler (TCD) velocities, who currently receive chronic transfusions to reduce the risk of primary stroke. For the alternative treatment regimen (hydroxyurea) to be declared non-inferior to the standard treatment regimen (transfusions), after adjusting for baseline differences, the hydroxyurea-treated group must have a mean TCD velocity similar to that observed with transfusion prophylaxis.

Detailed Description

Despite the clear results of the STOP and the follow-up STOP II trials, the use of chronic erythrocyte transfusions for primary stroke prevention in children with Sickle Cell Anemia (SCA) remains controversial for many practicing hematologists, as well as for patients and families. Transfusions have proven clinical efficacy in preventing first stroke in children with SCA and abnormal TCD velocities, but their indefinite use may still be difficult to justifY.
The risk of transfusion acquired iron overload is now recognized as a serious consequence of chronic erythrocyte transfusions in children with SCA. After one to two years of monthly transfusions, virtually every patient will have excess hepatic iron deposition that warrants intervention with chelation therapy. The effectiveness of iron chelation has not yet been realized, despite the availability of the oral chelator deferasirox (Exjade®), due to its lack of palatability and increasing recognition of serious drug-related toxicities including renal and hepatic dysfunction. Simply put, indefinite erythrocyte transfusions cannot be viewed as adequate and acceptable long-term therapy for primary stroke prevention in SCA. There is an urgent need to develop an equivalent effective alternative therapy for the prevention of primary stroke in children with SCA, specifically one that better manages iron overload and improves quality of life.

Trial Stopped: The study was stopped early due to successfully meeting the primary endpoint

Conditions

Interventions

  • Hydroxyurea (Hydrea® and Droxia® Other names Return to top Hydroxycarbamide )Drug
    Intervention Desc: Capsules (300 mg, 400 mg, or 500 mg) taken once daily liquid formulation (100 mg/mL)
    ARM 1: Kind: Experimental
    Label: Treatment Arm
    Description: Hydroxyurea will be provided as capsules or liquid

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary TCD Mean Velocity at 24 months on the index side 30 months Yes
Secondary TCD time-averaged mean velocity on the non-index side 30 months Yes
Secondary Primary stroke events 30 months Yes
Secondary Non-stroke neurological events 30 months Yes
Secondary Hepatic iron overload 30 months Yes
Secondary Effects on Quality of Life 30 months No
Secondary Functional status 30 months No
Secondary Neuropsychological decline 30 months No
Secondary Growth and development 30 months No
Secondary Transfusion events 30 months Yes
Secondary Hydroxyurea toxicities 30 Months Yes
Secondary Phlebotomy complications 30 months Yes
Secondary Liver MRI complications 30 months Yes
Secondary Safety endpoints of adverse events and clinical laboratory values 30 Months Yes

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