Realizing Effectiveness Across Continents With Hydroxyurea (REACH) (REACH)
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|ClinicalTrials.gov Identifier: NCT01966731|
Recruitment Status : Active, not recruiting
First Posted : October 22, 2013
Last Update Posted : August 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Drug: Hydroxyurea||Phase 1 Phase 2|
- To assess the feasibility of conducting a prospective research study using hydroxyurea therapy for SCA in sub-Saharan Africa (including adherence to monthly clinic visits and laboratory assessments, and medication compliance)
- To monitor the safety of hydroxyurea therapy, specifically documenting hematological toxicities (cytopenias) and serious infections (bacterial and malarial)
- To evaluate the benefits of hydroxyurea therapy, using both laboratory (e.g., fetal hemoglobin, hemoglobin, white blood cell count) and clinical parameters (e.g., pain, hospitalization, growth)
- To investigate the effects of hydroxyurea dose escalation on laboratory and clinical parameters
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||635 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Realizing Effectiveness Across Continents With Hydroxyurea (REACH): A Phase I/II Pilot Study Of Hydroxyurea For Children With Sickle Cell Anemia|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||August 2033|
|Estimated Study Completion Date :||August 2033|
After patient enrollment, a two-month pre-hydroxyurea evaluation phase will be used to perform baseline evaluations including nutritional and infectious assessments, and to provide supplements or treatments as deemed necessary. After the pre-hydroxyurea evaluation and supplementation phase, hydroxyurea dosing will be administered as a single daily dose, using capsules provided as a monthly supply in 200mg, 300mg, 400mg, or 500mg sizes.
Hydroxyurea will begin at 15-20 mg/kg PO daily. Six months of treatment will be given at the fixed dose, followed by another six months with dose escalation (2.5-5.0 mg/kg increments every 8 weeks) as tolerated to 20-30 mg/kg/day or MTD. The dose escalation phase will continue through the 12-month evaluation, after which hydroxyurea will continue in maintenance phase until the common treatment termination date. The daily dose will be calculated using available capsule sizes and a goal of 15-20 (17.5 ± 2.5) mg/kg/day based on weight. After 6 months of treatment, hydroxyurea will be titrated according to myelosuppression, and will be increased to 20-30 mg/kg/day or the maximum tolerated dose (MTD). Hydroxyurea dose escalation will occur in 5.0 ± 2.5 mg/kg/day increments.
- Safety [ Time Frame: 48 months ]An expected toxicity rate of 20% and acceptable toxicity rate of 30% were used for statistical calculations. After 53 participants at each site complete 3 months of therapy, if ≤15 participants have hematologic toxicity there is no early evidence against safety. If ≥15 of the initial participants experience toxicity, this is early evidence against safety. Future participants will begin at a lower dose of hydroxyurea (10 ± 2.5 mg/kg), with another 53 participants recruited for the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.
- Efficacy [ Time Frame: 4 Weeks (plus or minues one week) ]The efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values. Additional measures of laboratory efficacy will include changes in Hb, MCV, WBC, ANC, ARC, and bilirubin. Clinical events such as vaso-occlusive pain will be captured as secondary outcomes.
- Feasibility [ Time Frame: 4 Weeks (plus or minus one week) ]Hydroxyurea treatment will be dispensed only 35 days at a time, requiring a clinic visit every 4 ± 1 weeks. Medication adherence and the ability for families to adhere to monthly clinic visits are important feasibility outcomes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01966731
|Hospital Pediátrico David Bernardino|
|Congo, The Democratic Republic of the|
|Centre Hospitalier Monkole|
|Kinshasa, Congo, The Democratic Republic of the|
|KEMRI/Wellcome Trust Research|
|Ministry of Health Mbale Regional Hospital|
|Principal Investigator:||Russell Ware, MD, PhD||Children's Hospital Medical Center, Cincinnati|