Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Hydroxyurea.
- Who it may be relevant to
- Registry conditions: Sickle Cell Anemia in Children, Sickle Cell Disease. Basic parameters: 6 months — 12 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Angola
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
BrUOG 419 - Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)
Overview
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.
Interventions
- Drug Hydroxyurea
Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.
Primary outcome measures
- Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0 [Time frame: From start of study treatment through first 12 months of treatment.]
- Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0 [Time frame: From start of study treatment through treatment completion, approximately 24 months.]
Secondary outcome measures (1)
- Hematologic response at 12 months [Time frame: From start of study treatment through first 12 months of treatment.]
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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Angola · 1 center
- Hospital Geral dos Cajueiros — Luanda
Identifiers
NCT: NCT05285917 · BrUOG 419 · U01HL157872