Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)

Brown University

Status and phase: Enrolling; Phase 3

Conditions: Sickle Cell Anemia in Children; Sickle Cell Disease

Treatments: Drug: Hydroxyurea

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05285917

BrUOG 419

U01HL157872 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 6 months to 12 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Weight Based Starting Dose

Active Comparator group

Description:

25 mg/kg starting dose Hydroxyurea

Treatment:

Drug: Hydroxyurea

PK-guided starting dose

Experimental group

Description:

Individualized, PK-guided starting dose Hydroxyurea

Treatment:

Drug: Hydroxyurea