Therapeutic Efficacy and Safety of Artemether-Lumefantrine Plus Primaquine for Uncomplicated Plasmodium Falciparum Malaria and Chloroquine Plus Primaquine for Uncomplicated Plasmodium Vivax Malaria in Ethiopia: A Multi-center, Open-label Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,200
- 试验地点
- 1
- 主要终点
- Early Treatment Failure
研究概览
简要总结
Background: The WHO recommends monitoring the efficacy of antimalarial drugs at least once every two years after implementation. The Ethiopian Public Health Institute (EPHI), the research arm for the Ministry of Health (MOH), has been studying the safety and efficacy of antimalarial drugs for the past two decades. The national malaria diagnosis and treatment guideline of Ethiopia states first-line treatment for uncomplicated Plasmodium falciparum (P. falciparum) infection is artemether-lumefantrine (AL) with a single dose of primaquine (PQ) and for uncomplicated P. vivax infection chloroquine (CQ) with 14 days of PQ. This study aimed to evaluate the therapeutic efficacy of AL plus a single low dose of PQ for uncomplicated P. falciparum malaria and CQ plus 14 days of PQ for uncomplicated P. vivax malaria in six sentinel sites of Ethiopia.
Methods: This study will be conducted from October 2026 to June 2027 in six sentinel sites. A minimum of 100 patients each with uncomplicated P. falciparum or P. vivax malaria aged 6 months and above, will be enrolled at each of the six study sites and followed for 28 days for P. falciparum and 42 days for P. vivax for adequate clinical and parasitological response. Patients with microscopically confirmed P. falciparum mono-infection will be assigned to receive AL + PQ, and those with microscopically confirmed P. vivax mono-infection will be assigned to receive CQ + PQ. Clinical, parasitological, and hematologic parameters will be monitored for P. falciparum and P. vivax infections for up to a 28/42-day follow-up period and used to evaluate drug efficacy. Kaplan-Meier method survival analysis and pertinent descriptive analysis will be conducted using STATA considering P < 0.05 as statistically significant. Results from this research will be presented in text narration, tables and figures.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 6 months.
- •Microscopically confirmed uncomplicated P. falciparum mono-infection with an asexual parasite density of 1000-100,000 parasites/µL, or an uncomplicated P. vivax mono-infection with an asexual parasite density of 250-100,000 parasites/µL.
- •Presence of fever (axillary temperature ≥37.5°C) or a history of fever during the preceding 24 hours.
- •Residence within 20 km of the enrolling health facility (or within the defined study catchment area) and willingness to remain in the area for the duration of follow-up.
- •Body weight ≥5.0 kg.
- •Hemoglobin (Hb) concentration ≥ 8 g/dL.
- •Ability to swallow oral medication.
- •Ability and willingness (or that of a parent/legal guardian for children) to comply with the study protocol and scheduled follow-up visits.
- •Provision of written informed consent by the participant or a parent/legal guardian for minors. Where applicable, assent will be obtained from older children in accordance with national ethical requirements.
- •Willingness of women of reproductive age (12-49 years) to take a pregnancy test
排除标准
- •1. Presence of signs or symptoms of severe malaria or danger signs suggestive of severe malaria, as defined by the WHO (Annex I).
- •2. Severe malnutrition, defined as any of the following: weight-for-height or weight-for-age according to national/WHO criteria, bilateral pitting edema of nutritional origin, or mid-upper arm circumference (MUAC) <11.5 cm for children aged 6-59 months
- •Mixed Plasmodium species infection.
- •Moderate to severe anemia (hemoglobin <8 g/dL)
- •Presence of febrile illness due to causes other than malaria requiring alternative treatment (e.g., measles, acute lower respiratory tract infection, or severe diarrhea with dehydration).
- •6. Presence of a serious or chronic medical condition that may interfere with study participation or outcome assessment (e.g., cardiac, renal, hepatic disease, sickle cell disease, or HIV/AIDS).
- •7. Known pregnancy or pregnancy test positive or breastfeeding.
- •Women of childbearing potential who are unwilling or unable to use effective contraception during the study period, where applicable according to the study drug requirements.
- •9. Known hypersensitivity or allergy to the study medication or any alternative antimalarial treatment used in the study.
- •10. Current use of medications known to interfere with the pharmacokinetics, efficacy, or safety of the study antimalarial drugs (Annex II).
结局指标
主要结局
Early Treatment Failure
时间窗: Day 1 to Day 3
1\. Danger signs or severe malaria on day 1, day 2 or day 3 in the presence of parasitemia; or 2. Parasitemia on day 2 higher than on day 0, irrespective of axillary temperature; or 3. Parasitemia on day 3 with axillary temperature ≥37.5 ºC; or 4. Parasitemia on day 3 ≥25% of count on day 0.);
Late Clinical Failure
时间窗: Between Day 4 and 28 for P.f and Day 42 for P.v
1\. Danger signs or severe malaria in the presence of parasitemia on any day between day 4 and 28 for P.f or day 42 for P.v in patients who did not previously meet any of the criteria of Early Treatment Failure; or 2. Presence of parasitemia on any day between 4 and day 28 (day 42) with axillary temperature ≥37.5 ºC (or history of fever) in patients who did not previously meet any of the criteria of early treatment failure
Late Parasitological Failure
时间窗: Between Day 7 and Day 28 for P.f or Day 42 for P.v
Presence of parasitemia on any day between Day 7 and Day 28 for P.f or Day 42 for P.v and axillary temperature \<37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.
Adequate Clinical and Parasitological Response
时间窗: Day 28 for P.f or Day 42 for P.v
Adequate clinical and parasitological response during 28 days of follow-up for P. falciparum and 42 days of P. vivax. It is the absence of parasitemia on Day 28 for P.f or Day 42 for P.v irrespective of axillary temperature in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.
次要结局
未报告次要终点
研究者
Bokretsion Gidey
Mr
Ethiopian Public Health Institute