Realizing Effectiveness Across Continents With Hydroxyurea

NCT ID: NCT06171217

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 810 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-27
• Study Completion Date: 2033-10-04

Brief Summary

REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. 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.

Detailed Description

REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. 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. In the REACH prospective trial, the Original Cohort will receive long-term treatment while for the New Cohort, treatment will continue at least 4 years using PK-guided dosing after an initial 3-month screening period.

Conditions

Sickle Cell Disease; Children

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Original Cohort

The original REACH cohort continuing study treatment per the protocol schedule of evaluations.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

Hydroxyurea, approximately 20-30 mg/kg/day, with modifications for toxicity or for mild marrow suppression

New Cohort

Newly enrolled REACH participants consent, 3 months screening, and treatment per the protocol schedule of evaluations

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

Hydroxyurea 15-35 mg/kg/day based on PK-guided dosing, with modifications for toxicity for mild marrow suppression

Interventions

Hydroxyurea

Hydroxyurea, approximately 20-30 mg/kg/day, with modifications for toxicity or for mild marrow suppression

Intervention Type: DRUG

Hydroxyurea

Hydroxyurea 15-35 mg/kg/day based on PK-guided dosing, with modifications for toxicity for mild marrow suppression

Intervention Type: DRUG

Eligibility 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. In the Original Cohort, age range of 1.00-9.99 years, inclusive, at the time of enrollment (now age 5.5 - 17.5 years); age range 3.0-10.0 years for the New Cohort

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.

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

1. Anemia: Hb <4.0 g/dL

2. Anemia: Hb <6.0 g/dL with ARC <100 x 109/L

3. Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 g/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. In the Original Cohort, hydroxyurea use within 6 months before enrollment (temporary exclusion). In the New Cohort, the children should be hydroxyurea naïve, without any prior treatment exposure.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Russell Ware, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Hospital Pediátrico David Bernardino

Luanda, , Angola

Centre Hospitalier Monkole

Kinshasa, , Democratic Republic of the Congo

KEMRI/Wellcome Trust Research

Kilifi, , Kenya

Mbale Regional Hospital

Mbale, , Uganda

Countries

Angola; Democratic Republic of the Congo; Kenya; Uganda

Other Identifiers

U01HL133883

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013-4221b

Identifier Type: -

Identifier Source: org_study_id