Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 246
- 试验地点
- 1
- 主要终点
- Incidence of Clinical Malaria Per Patient Year
研究概览
简要总结
This is a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in children with sickle-cell anemia (SCA) at a single site in Homa Bay, Kenya. The study will enroll 246 children under 10 years of age, randomize participants 1:1:1 to one of three malaria chemoprevention regimens, and follow participants monthly for 12 months in order to record clinical episodes of malaria or SCA-related morbidity. Analyses will compare the efficacy of each regimen to prevent malaria and SCA morbidity.
详细描述
Purpose of the study:
Primary Objective: To compare the efficacy of daily proguanil with monthly sulfadoxine/pyrimethanine-amodiaquine (SP-AQ) and with monthly dihydroartemisinin-piperaquine (DP) on the incidence of falciparum malaria in children with SCA.
Secondary Objective: To compare the efficacy of these malaria chemoprevention strategies on the incidence of major complications of SCA.
Background & significance
Over 240,000 children with sickle cell anemia (SCA) are born in Africa annually. This number will increase to over 350,000 annual births of children with SCA by the year 2050. Without sophisticated medical care, SCA patients in African settings die at young ages: in a Western Kenya cohort of newborns, 25% of SCA children died before their 3rd birthday. Caring effectively for these children will be a major challenge for developing medical and public health systems in Africa including Kenya, and modeling studies suggest that the adequate provision of effective preventive care can substantially reduce the mortality of these children. Preventive care for SCA children must be evidence-based and tailored to the unique epidemiology of comorbidities in African settings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 12 months and less than 10 years at enrollment;
- •Current attendance at or willingness to attend the study SCA clinic at HBCH;
- •Residence in either Homa Bay County or the Rongo or Awendo sub-counties of Migori County;
- •Confirmed hemoglobin genotype of HbSS by electrophoresis, HPLC, or PCR;
- •No immediate, apparent, or reported plans to relocate residence from Homa Bay County or the Rongo or Awendo sub-counties of Migori County in the next 2 years;
- •Ability to take oral medication and be willing to adhere to the medication regimen or caregiver willingness to give the medical regimen as prescribed;
- •Ability and willingness of parent or legally authorized representative (LAR) to give informed consent;
- •Assent of child in those > 7 years.
排除标准
- •Taking routine antimalarial prophylaxis for another indication (including co-trimoxazole for HIV infection);
- •Temperature of ≥ 37.5C at screening or history of objective or subjective fever in the preceding 24 hours during screening;
- •Known allergy or sensitivity to sulfadoxine, pyrimethamine, amodiaquine, proguanil, dihydroartemisinin, piperaquine, artemether, lumefantrine, pencillin (if under 5 years old), or derivatives of these compounds;
- •Known chronic medical condition other than SCA (i.e. malignancy, HIV) requiring frequent medical attention;
- •Currently participating in another clinical research study, or having participated in one in the prior 30 days;
- •Living in the same household as a previously-enrolled study participant;
- •Chronic use of medications known to prolong the QT interval in children (see Appendix J);
- •Fridericia's corrected QT interval (QTcF) interval > 450msec.
研究组 & 干预措施
Proguanil Oral Tablet
Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis
干预措施: Proguanil Oral Tablet (Drug)
Sulfadoxine/Pyrimethanine-Amodiaquine
Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis.
干预措施: Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) (Drug)
Dihydroartemisinin-Piperaquine (DP)
DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis.
干预措施: Dihydroartemisinin-Piperaquine (DP) (Drug)
结局指标
主要结局
Incidence of Clinical Malaria Per Patient Year
时间窗: 12 months
The primary endpoint is the cumulative incidence of clinical malaria expressed as episodes per person-year at risk. Time at risk will begin when study participants are randomized and receive study drug (i.e. begin chemoprevention) and end when participants reach the end of the observation period.
次要结局
- Number of Participants With Severe Malaria(12 months)
- Number of Participants With Severe Anemia(12 months)
- Number of Participants With Hospitalization for Malaria(12 months)
- Number of Participants With Unconfirmed Malaria(12 months)
- Number of Participants With Fatal Malaria(12 months)
- Number of Participants With Painful Events(12 months)
- Number of Participants With Dactylitis(12 months)
- Number of Participants With Transfusions(12 months)
- Number of Participants With Acute Chest Syndrome(12 months)
- Number of Participants With All-cause Hospitalization(12 months)
- All-cause Deaths(12 months)
- Molecular Markers of Malaria Parasite Drug Resistance(12 months)
- Number of Participants With Light Microscopy (LM)-Positive Malaria(12 months)
- Number of Participants With Asymptomatic Parasitization(12 months)