Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age6-12
SponsorBrown University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Hydroxyurea
DrugHydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.
Treatment groups
400 Participants
are divided into 2 treatment groupsGroup A: Weight Based Starting DoseActive comparator 1 intervention
Group B: PK-guided starting doseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0
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.
Time frame
From start of study treatment through first 12 months of treatment.2
Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0
The clinical event rate with limited laboratory monitoring will be compared to the 3-months prior to hydroxyurea therapy.
Time frame
From start of study treatment through treatment completion, approximately 24 months.Secondary outcomes
1
Hematologic response at 12 months
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.
Time frame
From start of study treatment through first 12 months of treatment.Other outcomes
1
Health-Related Quality of Life Questionnaires
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.
Time frame
From start of study treatment through treatment completion, approximately 24 months.Sponsors and contacts
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Brown University
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Novartis
Collaborator
Source ClinicalTrials.gov