Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa

NCT ID: NCT05285917

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-15
• Study Completion Date: 2027-09-01

Brief Summary

Sickle cell anemia (SCA) is among the world's most common and devastating blood disorders, affecting more than 300,000 newborns per year. Most infants with SCA are born in the low-resource settings of sub- Saharan Africa, where an estimated 50-90% will die before 5 years of age due to lack of early diagnosis and appropriate care. Hydroxyurea is a safe and effective once-daily oral medication that has become the standard of care for the treatment of children with SCA in high-resource settings. There is now a growing body of evidence to support the safety and clinical benefits of hydroxyurea for the treatment of SCA in sub-Saharan Africa. The requirement for frequent laboratory monitoring, uncertainties about appropriate, most effective dosing, and the concern for hematologic laboratory toxicities, however, will continue to limit widespread hydroxyurea utilization and real-world effectiveness. The investigators have recently developed and prospectively evaluated an individualized, pharmacokinetics-guided hydroxyurea dosing strategy for children with SCA that has demonstrated optimal clinical and laboratory benefits with minimal toxicity. In this research study, the investigators aim to extend this precision medicine approach to Africa.

Detailed Description

The Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP) trial is a prospective, randomized clinical trial of hydroxyurea for 400 children with SCA in Luanda, Angola. The study will prospectively evaluate the safety and efficacy of hydroxyurea with limited laboratory monitoring and will bring precision medicine to children with SCA using several novel features including measurement of hydroxyurea using a battery-powered HPLC machine and individualized dose calculations using an automated computer-based algorithm. The objective of this study is to establish evidence-based guidelines for hydroxyurea in sub-Saharan Africa, including appropriate dosing and laboratory monitoring strategy with the goal of allowing for widespread use of hydroxyurea across sub-Saharan Africa, regardless of clinical or laboratory resources.

Conditions

Sickle Cell Anemia in Children; Sickle Cell Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Weight Based Starting Dose

25 mg/kg starting dose Hydroxyurea

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.

PK-guided starting dose

Individualized, PK-guided starting dose Hydroxyurea

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.

Interventions

Hydroxyurea

Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.

Intervention Type: DRUG

Other Intervention Names

Hydrea; Droxia

Eligibility Criteria

Inclusion Criteria

• Diagnosis of sickle cell anemia (HbSS or HbS/B0-thalassemia)
• Age 6 months- 12 years of age at enrollment
• Parent or guardian willing and able to provide written or informed consent
• Weight ≥ 7.5 kg (temporary exclusion)

Exclusion Criteria

• Splenomegaly with evidence of hypersplenism as defined by platelet count <150,000, hemoglobin <5 g/dL or absolute neutrophil count <1.0 x10^9/L
• Hydroxyurea use within the past 6 months
• Blood transfusion within the past 6 months (temporary exclusion)
• Pregnancy
• Pre-existing severe hematologic toxicity, as defined by platelet count <80,000, hemoglobin <4 regardless of ANC; hemoglobin <6 AND ARC <100; hemoglobin <7 AND ARC <80 x10^9/L (temporary exclusion)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Brown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick T McGann, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Rhode Island Hospital and Hasbro Children's Hospital

Locations

Hospital Geral dos Cajueiros

Luanda, , Angola

Site Status: RECRUITING

Countries

Angola

Central Contacts

BrUOG

Role: CONTACT

BrUOG@brown.edu

401-863-3000

Facility Contacts

Eugenia Alberto Mateus, MSN

Role: primary

Other Identifiers

U01HL157872

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BrUOG 419

Identifier Type: -

Identifier Source: org_study_id