Novel Use Of Hydroxyurea in an African Region With Malaria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Number of Malaria Episodes
研究概览
简要总结
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.
详细描述
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:
- Determine the incidence of malaria in children with sickle cell anemia treated with hydroxyurea vs. placebo
- Establish the frequency of hematologic toxicities and adverse events in children with sickle cell anemia treated with hydroxyurea vs. placebo
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Months 至 47 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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:
- •Hb <4.0 g/dL
- •Hb <6.0 g/dL AND ARC <100 x 10E9/L
- •Hb <7.0 g/dL AND ARC <80 x 10E9/L
- •Platelets <80 x 10E9/L
- •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
研究组 & 干预措施
Hydroxyurea
Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months
干预措施: Hydroxyurea (Drug)
Placebo
Fixed dose 20 ± 2.5 mg/kg/day, administered once a day in tablet form (100mg or scored 1000mg) for twelve months
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Malaria Episodes
时间窗: 12 months
Malaria is defined as the presence of P. falciparum or P. malariae on the peripheral smear of any child brought in for medical evaluation of fever. P. vivax, P. ovale and P. knowlesi are not known to be present in this region, but if a child is seen with suspected infection with any of these malaria parasites, this will also be recorded as a case of malaria. Incidence will be reported in the number of cases per 100 patient years.
次要结局
未报告次要终点
研究者
Chandy John
Professor of Pediatrics, Medicine, Microbiology and Immunology
Indiana University