Status:
TERMINATED
Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea
Lead Sponsor:
Children's Hospital Medical Center, Cincinnati
Collaborating Sponsors:
National Heart, Lung, and Blood Institute (NHLBI)
Boston Children's Hospital
Conditions:
Sickle Cell Anemia
Eligibility:
All Genders
4-15 years
Phase:
PHASE3
Brief Summary
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 abnorm...
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 cont...
Eligibility Criteria
Inclusion
- Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia,HbSOArab)
- Age range of 4.0-15.99 years, inclusive, at the time of enrollment
- Documented index (pre-treatment) abnormally high TCD Velocity by Transcranial Doppler ultrasonography. An abnormally high index TCD is defined as TCD V greater than or equal to 200 cm/sec, or abnormally high TCDi V greater than or equal to185cm/sec, or TCD maximum V greater than or equal to 250 cm/sec.
- At least 12 months of chronic monthly erythrocyte transfusions since the index abnormal TCD examination
- Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) for the past 6 months before enrollment
- Parent or guardian willing and able to provide informed consent with verbal or written assent from the child
- Ability to comply with study related treatments, evaluations, and follow-up
Exclusion
- Completed overt clinical stroke or TIA
- Inability to obtain TCD velocities due to anatomical abnormalities such as a) Inadequate bone windows b) Previous revascularization procedures (e.g., EDAS)
- Known severe vasculopathy or moya-moya disease on brain MRA
- Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following: a) Multiple RBC alloantibodies making cross-matching difficult or impossible b) RBC autoantibodies making cross-matching difficult or impossible c) Religious objection to transfusions that preclude their chronic use d) Non-compliance with transfusions over the past 6 months before enrollment (temporary exclusion)
- Inability to take or tolerate daily oral hydroxyurea, including a) Known allergy to hydroxyurea therapy b) Positive serology to HIV infection c) Malignancy d) Current lactation e) Previous stem cell transplant or other myelosuppressive therapy
- Clinical and laboratory evidence of hypersplenism (temporary exclusions): a) Palpable splenomegaly greater than 5cm below the left costal margin AND b) Transfusion requirement greater than 250 mL/kg over the previous 12 months
- Abnormal laboratory values at initial evaluation (temporary exclusions): a) Pre-transfusion hemoglobin concentration less than 8.0 gm/dL b) WBC count less than 3.0 x 10\^9/L c) Absolute neutrophil count (ANC) less than 1.5 x 10\^9/L d) Platelet count less than 100 x 10\^9/L e) Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL
- Current participation in other therapeutic clinical trials
- Current use of other therapeutic agents for sickle cell disease (e.g., arginine, decitabine, magnesium). Subjects must have been off hydroxyurea for at least 3- months prior to enrollment.
- Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the CI makes participation ill-advised.
- Inability or unwillingness to complete required screening and exit studies, including TCD ultrasonography, brain MRI/MRA, liver MRI and blood tests.
- A sibling enrolled in TWiTCH
- Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active (male OR female).
Key Trial Info
Start Date :
August 1 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 1 2015
Estimated Enrollment :
159 Patients enrolled
Trial Details
Trial ID
NCT01425307
Start Date
August 1 2011
End Date
November 1 2015
Last Update
July 22 2020
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