Realizing Effectiveness Across Continents With Hydroxyurea (REACH) (REACH)

June 12, 2026 updated by: Children's Hospital Medical Center, Cincinnati

REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA (REACH): A PHASE I/II PILOT STUDY OF HYDROXYUREA FOR CHILDREN WITH SICKLE CELL ANEMIA

REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for for pediatric patients with sickle cell anemia (SCA). The short-term goal is to obtain critical pilot data regarding the feasibility, safety, and benefit of hydroxyurea for children with SCA in multiple distinct research settings in Africa. Based on that information, the longer-term goal is to make hydroxyurea more widely available for children with SCA in Africa, particularly those identified with SCA through expanded newborn screening programs.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

STUDY OBJECTIVES

  1. 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)
  2. To monitor the safety of hydroxyurea therapy, specifically documenting hematological toxicities (cytopenias) and serious infections (bacterial and malarial)
  3. 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)
  4. To explore the pharmacokinetic and genetic basis for any observed inter-patient variability in the clinical or laboratory response to hydroxyurea.
  5. To evaluate the economic cost of providing hydroxyurea therapy in the REACH study sites.
  6. To investigate the effects of hydroxyurea dose escalation on laboratory and clinical parameters

Study Type

Interventional

Enrollment (Actual)

635

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Angola
      • Luanda, Angola
        • Hospital Pediátrico David Bernardino
  • Democratic Republic of the Congo
      • Kinshasa, Democratic Republic of the Congo
        • Centre Hospitalier Monkole
  • Kenya
      • Kilifi, Kenya
        • KEMRI/Wellcome Trust Research
  • Uganda
      • Mbale, Uganda
        • Ministry of Health Mbale Regional Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 10 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear)
  2. Age range of 1.00-9.99 years, inclusive, at the time of enrollment
  3. Weight at least 10.0 kg at the time of enrollment
  4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements
  5. Willingness to comply with all study-related treatments, evaluations, and follow-up

Exclusion Criteria

  1. Known medical condition making participation ill-advised, (e.g., acute or chronic infectious disease, HIV, or malignancy)
  2. Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or height for age >3 z-scores below the median WHO growth standards, as defined in Appendix I)

  3. Pre-existing severe hematological toxicity (temporary exclusions)

    1. Anemia: Hb <4.0 gm/dL
    2. Anemia: Hb <6.0 gm/dL with ARC <100 x 109/L
    3. Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 gm/dL
    4. Thrombocytopenia: Platelets <80 x 109/L
    5. Neutropenia: ANC <1.0 x 109/L
  4. Blood transfusion within 60 days before enrollment (temporary exclusion)
  5. Hydroxyurea use within 6 months before enrollment (temporary exclusion)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hydroxyurea
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.
Drug: Hydroxyurea
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.
Other Names:
  • Hydrea
  • Droxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Dose Limiting Toxic Events
Time Frame: 3 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 of the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Hydroxyurea
Time Frame: Assessed every 4 ± 1 weeks up to 204 months
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.
Assessed every 4 ± 1 weeks up to 204 months
Medication Adherence and the Ability for Families to Adhere to Monthly Clinic Visits Are Important Feasibility Outcomes
Time Frame: Assessed every 4 ± 1 weeks up to 204 months
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
Assessed every 4 ± 1 weeks up to 204 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Russell Ware, MD, PhD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Actual)

July 1, 2018

Study Completion (Estimated)

August 1, 2033

Study Registration Dates

First Submitted

October 4, 2013

First Submitted That Met QC Criteria

October 17, 2013

First Posted (Estimated)

October 22, 2013

Study Record Updates

Last Update Posted (Actual)

June 30, 2026

Last Update Submitted That Met QC Criteria

June 12, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-4221

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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