Realizing Effectiveness Across Continents With Hydroxyurea (REACH)

Cincinnati Children's Hospital Medical Center

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Sickle Cell Disease

Treatments: Drug: Hydroxyurea

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01966731

2013-4221

Details and patient eligibility

About

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.

Full 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

Enrollment: 635 patients

Sex: All

Ages: 1 to 10 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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635 participants in 1 patient group

Hydroxyurea

Experimental group

Description:

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.

Treatment:

Drug: Hydroxyurea