Ethiopian Antimalarial Therapeutic Efficacy Study 2026

NCT07840898 | Not Yet Recruiting

• 1 other identifier: EPHI-IRB-688-2026
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Plasmodium Vivax Malaria Without Complication; Plasmodium Falciparum Malaria (Uncomplicated)

Keywords

P. falciparum; P. vivax; Therapeutic Efficacy; Ethiopia

Outcome Measures

Primary Outcomes (4)

• Early Treatment Failure

  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.);

  Day 1 to Day 3

• Late Clinical Failure

  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

  Between Day 4 and 28 for P.f and Day 42 for P.v

• Late Parasitological Failure

  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.

  Between Day 7 and Day 28 for P.f or Day 42 for P.v

• Adequate Clinical and Parasitological Response

  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.

  Day 28 for P.f or Day 42 for P.v

Interventions

Artemether-Lumefantrine + Primaquine and Chloroquine + Primaquine DRUG

For uncomplicated P. falciparum patients, 3 days of a bid dose of Artemether-lumefantrine with a single low dose of primaquine. For uncomplicated P. vivax patients, 3 days dose of chloroquine with 14 days primaquine will be given under observation

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients residing in malaria-endemic areas who self-present to the outpatient departments of the selected health facilities with uncomplicated P. falciparum or P. vivax malaria. Only patients living within the catchment area of the participating health facilities (within a 20 km radius) will be eligible for enrollment. This geographical restriction is intended to facilitate active follow-up through home visits for participants who fail to attend their scheduled follow-up visits, thereby minimizing loss to follow-up and ensuring complete outcome assessment.

You may qualify if:

• 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

You may not qualify if:

• \. Presence of signs or symptoms of severe malaria or danger signs suggestive of severe malaria, as defined by the WHO (Annex I).
• \. 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 3. Mixed Plasmodium species infection. 4. Moderate to severe anemia (hemoglobin \<8 g/dL) 5. 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).
• \. 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).
• \. Known pregnancy or pregnancy test positive or breastfeeding. 8. 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.
• \. Known hypersensitivity or allergy to the study medication or any alternative antimalarial treatment used in the study.
• \. Current use of medications known to interfere with the pharmacokinetics, efficacy, or safety of the study antimalarial drugs (Annex II).

Sponsors & Collaborators

• PATH: collaborator
• US government: collaborator
• Ethiopian Public Health Institute: lead
• National Centre for Disease Prevention and Control: collaborator

Study Sites (1)

Ethiopian Public Health Institute

Addis Ababa, Ethiopia

Location

Related Publications (1)

• 1. WHO. World malaria report 2025. Geneva: World Health Organization; 2025. 2. Ministry of Health. National Malaria Elimination Strategic Plan: 2021-2025. Addis Ababa: Ethiopia Ministry of Health; 2020. 3. PMI. U.S. President's Malaria Initiative Ethiopia Malaria Operational Plan FY 2024.: President's Malaria Initiative; 2024. 4. WHO. Guidelines for the Treatment of Malaria. Geneva: World Health Organization; 2015. 5. WHO. WHO guidelines for malaria. Geneva: World Health Organization; 2025. 6. White NJ. Antimalarial drug resistance. J Clin Invest. 2004;113(8):1084-92. 7. Talisuna AO, Bloland P, D'Alessandro U. History, dynamics, and public health importance of malaria parasite resistance. Clin Microbiol Rev. 2004;17(1):235-54. 8. Bloland PB, Kazembe PN, Oloo AJ, Himonga B, Barat LM, Ruebush TK. Chloroquine in Africa: critical assessment and recommendations for monitoring and evaluating chloroquine therapy efficacy in sub-Saharan Africa. Trop Med Int Health. 1998;3(7):543-52. 9. Trape JF, Pison G, Preziosi MP, Enel C, Desgrees du Lou A, Delaunay V, et al. Impact of chloroquine resistance on malaria mortality. C R Acad Sci III. 1998;321(8):689-97. 10. Laxminarayan R. Act now or later? Economics of malaria resistance. The American journal of tropical medicine and hygiene. 2004;71(2 Suppl):187-95. 11. Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, et al. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet. 2000;356(9226):297-302. 12. Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, et al. Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother. 2013;57(2):818-26. 13. van der Pluijm RW, Imwong M, Chau NH, Hoa NT, Thuy-Nhien NT, Thanh NV, et al. Determinants of dihydroartemisinin-piperaquine treatment failure in Pla

  BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Dried Blood Spot

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination; Primaquine; Chloroquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mr

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): October 20, 2026
• Primary Completion (Estimated): February 20, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: September 25, 2026

Record last verified: 2026-09

Locations

ET (1)