PUSHUP: Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Weight Based Starting Dose 1 25 mg/kg starting dose Hydroxyurea |
Drug: Hydroxyurea
Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.
|
| Experimental: PK-guided starting dose Individualized, PK-guided starting dose Hydroxyurea |
Drug: Hydroxyurea
Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events (grade ≥ 3) as assessed by CTCAE v5.0 [From start of study treatment through treatment completion, approximately 24 months.]
To evaluate the safety of hydroxyurea for children with SCA in sub-Saharan Africa with limited laboratory monitoring.
Other Outcome Measures
- Health-Related Quality of Life Questionnaire [From start of study treatment through treatment completion, approximately 24 months.]
To evaluate the utility and validity of two established measures of health-related quality of life (HRQoL) for patients and families affected by SCA in Angola before and after hydroxyurea treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of sickle cell anemia (HbSS or HbS/B0-thalassemia)
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Age 6 months- 12 years of age at enrollment
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Parent or guardian willing and able to provide written or informed consent
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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
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Hydroxyurea use within the past 6 months
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Blood transfusion within the past 6 months (temporary exclusion)
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Pregnancy
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Pre-existing severe hematologic toxicity, as defined by platelet count <50,000, hemoglobin <5 g/dL or absolute neutrophil count <0.75 x 10^9/L (temporary exclusion)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Geral dos Cajueiros | Luanda | Angola |
Sponsors and Collaborators
- Brown University
- National Heart, Lung, and Blood Institute (NHLBI)
- Novartis
Investigators
- Principal Investigator: Patrick T McGann, MD, MS, Rhode Island Hospital and Hasbro Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BrUOG 419
- U01HL157872