Novel Use Of Hydroxyurea in an African Region With Malaria

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-30

Study Completion Date

2017-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Multiple studies have shown that hydroxyurea has clinical efficacy in preventing acute painful episodes and reducing the need for blood transfusions in children with sickle cell anemia (SCA), but no study has been conducted in malaria endemic regions of sub-Saharan Africa, the areas with the most children with SCA.

The primary goal of this study is to investigate the safety and efficacy of hydroxyurea for children with SCA in a malaria endemic region within sub-Saharan Africa.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Optimizing Hydroxyurea Therapy in Children With SCA In Malaria Endemic Areas

NCT03128515

Sickle Cell Anemia Sickle Cell Disease Malaria

COMPLETED PHASE3

Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

NCT00305175

Sickle Cell Disease

COMPLETED

Hydroxyurea to Prevent Brain Injury in Sickle Cell Disease

NCT01389024

Sickle Cell Disease Stroke

COMPLETED PHASE2

Moderate Dose Hydroxyurea for Secondary Stroke Prevention in Children With Sickle Cell Disease in Sub-Saharan Africa

NCT02675790

Sickle Cell Disease Sickle Cell Anemia Stroke

COMPLETED PHASE3

Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa

NCT05285917

Sickle Cell Anemia in Children Sickle Cell Disease

RECRUITING PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The risk of malaria and hematologic toxicities from hydroxyurea in children with SCA living in malaria endemic regions is unknown.

Some changes associated with hydroxyurea treatment (increased nitric oxide and HbF) would be expected to protect against malaria, but the data on hydroxyurea-related endothelial changes thought to be important in malaria pathogenesis (e.g. intracellular adhesion molecule (ICAM)-1, von Willebrand factor (VWF), tumor necrosis factor (TNF)-α) is unclear, with some studies suggesting that these factors might be increased with hydroxyurea and others suggesting no difference or a decrease.

The specific aims of this study are as follows:

1. Determine the incidence of malaria in children with sickle cell anemia treated with hydroxyurea vs. placebo
2. Establish the frequency of hematologic toxicities and adverse events in children with sickle cell anemia treated with hydroxyurea vs. placebo
3. Define the relationship between hydroxyurea treatment and fetal hemoglobin (HbF), soluble ICAM-1 (sICAM-1) and nitric oxide (NO) levels, and between levels of these factors and risk of subsequent malaria.

Two hundred children from the Mulago Hospital Sickle Cell Clinic (MHSCC) in Kampala, Uganda will be randomized to receive either hydroxyurea (100) or placebo (100) at a fixed dose of 20 ± 2.5 mg/kg/day. The primary study endpoints will be evaluated after twelve months of study treatment. After twelve months of study treatment, children will enter a follow-up phase during which they can receive an additional twelve months of open-label hydroxyurea treatment if they/their parents wish to do so after consultation with local physicians at the MHSCC.

The working hypotheses of this research study are:

1. The incidence of malaria is not greater in children with SCA treated with hydroxyurea than those treated with placebo
2. Children with SCA treated with hydroxyurea will have more medication-related hematologic toxicities, such as neutropenia, but no increase in SCA-related adverse events (e.g. pain crises, hospitalizations, requirement for blood transfusion) compared to children treated with placebo
3. Hydroxyurea will increase HbF and plasma NO levels and decrease plasma sICAM-1 levels; HbF and plasma NO levels will inversely correlate, and plasma sICAM-1 levels will positively correlate, with subsequent malaria incidence

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Sickle Cell Anemia Sickle Cell Disease Malaria

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hydroxyurea

Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months

Group Type EXPERIMENTAL

Hydroxyurea

Intervention Type DRUG

Placebo

Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Hydroxyurea

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Siklos Hydroxycarbamide

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Pediatric subjects with documented sickle cell anemia (HbSS supported by hemoglobin electrophoresis or by peripheral blood smear showing sickled red blood cells)
* Age range of 1.00-3.99 years, inclusive, at the time of enrollment
* Weight at least 5.0 kg at the time of enrollment
* Willingness to comply with all study-related treatments, evaluations, and follow up

Exclusion Criteria

* Known chronic medical condition (e.g., HIV, malignancy, active clinical tuberculosis)
* Severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or weight-for-length/height \> 3 z-scores below the median WHO growth standards)
* Pre-existing severe hematological toxicity:

1. Hb \<4.0 g/dL
2. Hb \<6.0 g/dL AND ARC \<100 x 10E9/L
3. Hb \<7.0 g/dL AND ARC \<80 x 10E9/L
4. Platelets \<80 x 10E9/L
5. ANC \<1.0 x 10E9/L
* Alanine transaminase (ALT) or creatinine \>2 times the upper limit of normal for age
* Blood transfusion within 30 days prior to enrollment

Minimum Eligible Age

12 Months

Maximum Eligible Age

47 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No