Clinical trial NCT05285917: Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
Official title: BrUOG 419 - Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Anemia in Children
Sickle Cell Disease
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Novartis
First posted: 2022-03-18
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0
timeFrame: From start of study treatment through first 12 months of treatment.
measure: Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0
timeFrame: From start of study treatment through treatment completion, approximately 24 months.
Secondary outcomes:
measure: Hematologic response at 12 months
timeFrame: From start of study treatment through first 12 months of treatment.
Other outcomes:
measure: Health-Related Quality of Life Questionnaires
timeFrame: From start of study treatment through treatment completion, approximately 24 months.
Locations:
city: Luanda
country: Angola
facility: Hospital Geral dos Cajueiros
Study officials:
affiliation: Rhode Island Hospital and Hasbro Children's Hospital
name: Patrick T McGann, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: