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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
277

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Didier Menard

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 7, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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