Artemisinin Partial Resistance in Ethiopian Plasmodium Falciparum: A Multisite Clinical, Molecular and In Vitro Study (ETH-ART-R)

April 7, 2026 updated by: Didier Menard

Confirmation of Artemisinin Partial Resistance in Plasmodium Falciparum Using WHO Criteria: A Multisite Clinical, Molecular and Phenotypic Study Across Five Sentinel Sites in Ethiopia, 2024-2025

Artemisinin-based combination therapies (ACTs) are the main treatment for falciparum malaria in Africa. Artemisinin partial resistance (ART-R), characterized by delayed parasite clearance after treatment, has been confirmed in four sub-Saharan African countries. In Ethiopia, molecular surveys have detected the Pfkelch13 R622I mutation associated with ART-R at multiple sites, but no study has yet combined clinical, molecular, and in vitro evidence to confirm ART-R per WHO criteria. This multisite study conducted across five sentinel sites in Ethiopia (2024-2025) assessed day-3 parasite positivity after artemether-lumefantrine treatment, Pfkelch13 genotyping, and ring-stage survival assay on culture-adapted field isolates, to determine whether ART-R is confirmed in Ethiopian Plasmodium falciparum populations.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study integrated three WHO-required lines of evidence to confirm artemisinin partial resistance (ART-R) in Ethiopia: (1) clinical evidence through day-3 parasite positivity assessment after artemether-lumefantrine treatment in therapeutic efficacy studies; (2) molecular evidence through Pfkelch13 propeller domain genotyping; and (3) phenotypic in vitro evidence through ring-stage survival assay (RSA0-3h) on culture-adapted field isolates. Five sentinel sites were selected across malaria-endemic regions of Ethiopia. Blood samples were collected at enrollment (day 0) and day 3. Isolates were cryopreserved and shipped to France (Strasbourg) for RSA.

Study Type

Interventional

Enrollment (Actual)

277

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ethiopia
      • Bako, Ethiopia
        • Bako Health Center
      • Kechemo, Ethiopia
        • Workamba Health Center
      • Metehara, Ethiopia
        • Metahara Health Center
      • Rama, Ethiopia
        • Rama Health Center
    • Tigray
      • Mersa, Tigray, Ethiopia
        • Mehoni Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 6 months
  • Microscopically confirmed uncomplicated Plasmodium falciparum monoinfection
  • Axillary temperature ≥ 37.5°C or history of fever in the past 24 hours
  • Ability to take oral medication
  • Written informed consent from patient or parent/guardian
  • Residence in the study area with intention to remain during follow-up

Exclusion Criteria:

  • Severe or complicated malaria (WHO criteria)
  • Mixed Plasmodium infection
  • Pregnancy or breastfeeding
  • Known hypersensitivity to artemether-lumefantrine
  • Antimalarial treatment in the 4 weeks prior to enrollment
  • Severe malnutrition
  • Concomitant febrile illness other than malaria requiring systemic treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Artemether-Lumefantrine
Patients with uncomplicated Plasmodium falciparum malaria received artemether-lumefantrine (AL) twice daily for 3 days per Ethiopian national treatment guidelines, with clinical follow-up on days 0 and 3.
Drug: Artemether-Lumefantrine Tab 20-120mg
Artemether-lumefantrine (Coartem) administered orally twice daily for 3 days at weight-based dosing per Ethiopian national malaria treatment guidelines.
Other Names:
  • Coartem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Day-3 Parasite Positivity Rate
Time Frame: Day 3 (72 hours after treatment initiation)
Proportion of patients with microscopically detectable Plasmodium falciparum parasitaemia on day 3 (72 ± 2 hours) after initiation of artemether-lumefantrine treatment, assessed by Giemsa-stained thick blood smear examination.
Day 3 (72 hours after treatment initiation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of Pfkelch13 R622I Mutation
Time Frame: Day 0 (enrollment)
Proportion of day-0 samples carrying the validated Pfkelch13 R622I mutation, assessed by targeted amplicon sequencing.
Day 0 (enrollment)
Ring-Stage Survival Rate
Time Frame: Assessed on culture-adapted isolates collected at Day 0
In vitro survival rate of culture-adapted field isolates after 6-hour exposure to 700 nM dihydroartemisinin, assessed by ring-stage survival assay (RSA0-3h). Resistance threshold: survival rate >1%.
Assessed on culture-adapted isolates collected at Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Didier Menard

Investigators

  • Principal Investigator: Didier Menard, Professor, University Hospital, Strasbourg, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2024

Primary Completion (Actual)

October 30, 2025

Study Completion (Actual)

April 7, 2026

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 7, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ETH-ARTR-2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) underlying the results reported in the published article will be made available upon reasonable request to the corresponding author, following publication. Data will include anonymized clinical outcome data, Pfkelch13 genotyping results, and ring-stage survival assay results.

IPD Sharing Time Frame

Beginning 6 months after publication

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal. Requests should be directed to the corresponding author. Data will be shared after signing a data access agreement.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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