Realizing Effectiveness Across Continents With Hydroxyurea (REACH)

NCT01966731 | Active Not Recruiting Phase 1 Results DMC

• 1 other identifier: 2013-4221
• Study Type: interventional
• Target: 635
• Locations: 4 countries
• Sites: 4

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Africa

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Dose Limiting Toxic Events

  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 Outcomes (2)

• Efficacy of Hydroxyurea

  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

  Assessed every 4 ± 1 weeks up to 204 months

Study Arms (1)

Hydroxyurea

EXPERIMENTAL

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

Interventions

Hydroxyurea DRUG

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.

Also known as: Hydrea, Droxia

Hydroxyurea

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Known medical condition making participation ill-advised, (e.g., acute or chronic infectious disease, HIV, or malignancy)
• 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)
• Anemia: Hb \<4.0 gm/dL
• Anemia: Hb \<6.0 gm/dL with ARC \<100 x 109/L
• Reticulocytopenia: ARC \<80 x 109/L with Hb \<7.0 gm/dL
• Thrombocytopenia: Platelets \<80 x 109/L
• Neutropenia: ANC \<1.0 x 109/L

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (4)

Hospital Pediátrico David Bernardino

Luanda, Angola

Location

Centre Hospitalier Monkole

Kinshasa, Democratic Republic of the Congo

Location

KEMRI/Wellcome Trust Research

Kilifi, Kenya

Location

Ministry of Health Mbale Regional Hospital

Mbale, Uganda

Location

Related Publications (5)

• Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.

  PMID: 41026975 DERIVED

• Aygun B, Lane A, Smart LR, Santos B, Tshilolo L, Williams TN, Olupot-Olupot P, Stuber SE, Tomlinson G, Latham T, Ware RE; REACH Investigators. Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2024 Jun;11(6):e425-e435. doi: 10.1016/S2352-3026(24)00078-4. Epub 2024 Apr 30.

  PMID: 38701812 DERIVED

• Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A, Aygun B, Stuber SE, Latham TS, McGann PT, Ware RE; REACH Investigators. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2019 Jan 10;380(2):121-131. doi: 10.1056/NEJMoa1813598. Epub 2018 Dec 1.

  PMID: 30501550 DERIVED

• McGann PT, Williams TN, Olupot-Olupot P, Tomlinson GA, Lane A, Luis Reis da Fonseca J, Kitenge R, Mochamah G, Wabwire H, Stuber S, Howard TA, McElhinney K, Aygun B, Latham T, Santos B, Tshilolo L, Ware RE; REACH Investigators. Realizing effectiveness across continents with hydroxyurea: Enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa. Am J Hematol. 2018 Aug;93(4):537-545. doi: 10.1002/ajh.25034. Epub 2018 Jan 27.

  PMID: 29318647 DERIVED

• McGann PT, Tshilolo L, Santos B, Tomlinson GA, Stuber S, Latham T, Aygun B, Obaro SK, Olupot-Olupot P, Williams TN, Odame I, Ware RE; REACH Investigators. Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub-Saharan Africa: Rationale and Design of the REACH Trial. Pediatr Blood Cancer. 2016 Jan;63(1):98-104. doi: 10.1002/pbc.25705. Epub 2015 Aug 14.

  PMID: 26275071 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Results Point of Contact

• Title: Russell Ware, MD, PhD
• Organization: Cincinnati Children's Hospital Medical Center

russell.ware@cchmc.org

(513) 803-1108

Study Officials

• Russell Ware, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After enrollment, a two-month screening phase was used to perform baseline evaluations including nutritional and infectious assessments, along with supplements and treatments as deemed necessary by local guidelines (e.g., penicillin, pneumococcal immunization, Vitamin A and albendazole/mebendazole treatment per WHO recommendations, malaria prophylaxis, and iron/folate supplementation)

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 22, 2013
• Study Start: June 1, 2014
• Primary Completion: July 1, 2018
• Study Completion (Estimated): August 1, 2033
• Last Updated: May 14, 2025
• Results First Posted: November 9, 2020

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AN (1); UG (1); DE (1); KE (1)