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NCT Number: NCT05285917

Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa

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.

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Key information

Conditions

Sickle Cell Anemia in Children Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Sickle Cell Disease

Age range

6 month–12 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Geral dos Cajueiros

Luanda, Angola

Location status: Recruiting

Location contact

Eugenia Alberto Mateus, MSN

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Hydroxyurea

Drug

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

Other names: Hydrea, Droxia

Primary outcomes

  1. 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.

    These events will primarily include vaso-occlusive painful events, acute chest syndrome, stroke, acute splenic sequestration, and death. Data regarding adverse events, including severity grade and relatedness to SCA will be determined on site by the local investigator. All events will be centrally adjudicated by a blinded hematologist who is not a primary study investigator (Medical Safety Monitor) for inclusion in this endpoint.

  2. 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.

    The clinical event rate with limited laboratory monitoring will be compared to the 3-months prior to hydroxyurea therapy.

Secondary outcomes

  1. Hematologic response at 12 months

    Time frame: From start of study treatment through first 12 months of treatment.

    As measured by %HbF, proportion of participants in each arm with HbF ≥ 30%, hemoglobin, absolute reticulocyte count, absolute neutrophil count, platelet count, and mean corpuscular volume), hematologic laboratory toxicities (dose limiting toxicities defined a priori), hospitalizations, death, and all adverse events grade ≥ 3 (SCA and non-SCA related) as assessed by CTCAE v5.0.

Other outcomes

  1. Health-Related Quality of Life Questionnaires

    Time frame: 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. we will evaluate the Pediatric Quality of Life Sickle Cell Disease (PedsQL SCD) module for children ≥ 2 years of age and the PedsQL™ Family Impact Module for families of all enrolled participants. We will also utilize the International Sickle Cell World Assessment Survey (SWAY). These tools are available in the Portuguese language; for consistency and to account for the likely low literacy rate in the population, all surveys will be administered verbally to participants by study staff, recorded on paper or via tablet. We will compare results before and after hydroxyurea treatment. We will compare results to each other and to the published literature from other SCA populations.

Study contacts

Contact information is provided by the study sponsor or research team.

BrUOG

CONTACT

[email protected]

401-863-3000

Sponsors and collaborators

Lead sponsor

Brown University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)
  • Novartis

Registry information

Official study title

BrUOG 419 - Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSHUP)

Acronym: PUSHUP

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Mar 18, 2022
Registry last updated
Apr 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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