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Malaria FalciparumNCT07362498

Health Systems Implementation and Molecular Surveillance of Multiple First-Line Treatments for Uncomplicated Malaria in Western Kenya

An observational study of Malaria Falciparum, run by Strathmore University at 2 sites in Kenya.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This implementation study evaluated the health systems feasibility, economic costs, and stakeholder acceptability of deploying multiple first-line therapies (MFTs) that were of the artemisinin-based combination therapies (ACTs) type, for uncomplicated malaria in Western Kenya. Read more about this study

Who is it for?
Ages 5 years and older
Conditions the study is for
Malaria Falciparum
What is being tested?
Artemether + Lumefantrine, Dihydroartemisin-piperaquine and Artesunate-Amodiaquine (AS-AQ)
Type of treatment
Pill or oral medicine
How many people
316 participants
Where
2 sitesKenya
Study dates
1 Jun 2020to 31 Jan 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Patients diagnosed with uncomplicated Plasmodium falciparum malaria at participating government and faith-based health facilities in Homa Bay County and Migori County, Western Kenya, a malaria-endemic region with high transmission intensity.

Who may be able to join

  • Age 5 years or older
  • Clinical diagnosis of uncomplicated malaria
  • Confirmed Plasmodium falciparum infection by rapid diagnostic test (RDT) or microscopy
  • Presenting at participating health facility for malaria treatment
  • Able and willing to provide informed consent (or parental/guardian consent for minors under 18 years)
  • Resident of study catchment area
  • For molecular surveillance substudy: willingness to provide dried blood spot sample

Who cannot join

  • Pregnant women (due to contraindications for some study medications in first trimester and lack of safety data)
  • Children under 5 years of age (due to lack of pediatric formulations for some study medications)
  • Severe or complicated malaria requiring parenteral treatment or hospitalization
  • Known hypersensitivity or contraindication to any of the study artemisinin-based combination therapies
  • Unable to take oral medications
  • Previous participation in current treatment episode (repeat visits)
  • Concurrent participation in other interventional malaria treatment studies

Trial locations and contacts

2 sites in 1 country.

Kenya2 sites
  • Homa Bay County Health Facilities

    Homa Bay, Homa Bay County, 40300

  • Migori County Teaching and Referral Hospital

    Migori, Migori County Kenya, 40400

Other trials in Kenya

About this study

Official title: Spatiotemporal Dynamics of Antimalarial Drug Resistance in Western Kenya During a Pilot Multiple First-line Treatment for Uncomplicated Malaria Study: Molecular Evidence of Resistance Saturation and Emerging Artemisinin Tolerance

This implementation study evaluated the health systems feasibility, economic costs, and stakeholder acceptability of deploying multiple first-line therapies (MFTs) that were of the artemisinin-based combination therapies (ACTs) type, for uncomplicated malaria in Western Kenya. The study included a nested observational molecular surveillance of antimalarial resistance markers in Plasmodium falciparum parasites. The implementation program involved adaptive cycling of four ACTs across 28 health facilities over 28 months (June 2020 - October 2022) with and extension to January 2024 in one geographic area (Mfangano Island). Health systems outcomes (feasibility, costs, acceptability) are reported in Cole et al., Malaria Journal 2024. Molecular surveillance outcomes (resistance marker prevalence and temporal trends) are reported in a companion manuscript currently under peer-review.

Read the detailed description

BACKGROUND: Artemisinin-based combination therapies (ACTs) are first-line treatment for uncomplicated malaria in sub-Saharan Africa, but emerging artemisinin partial resistance threatens efficacy. Multiple first-line treatments (MFTs) represent a proposed strategy to delay resistance emergence by deploying several ACTs simultaneously, sequentially, or using other strategies rather than relying on a single first-line therapy.

STUDY DESIGN: This 28-month implementation program (June 2020 - October 2022) with and extension only on Mfangano Island until January 2024, deployed adaptive cycling of four artemisinin-based combinations across health facilities in Western Kenya using geographic allocation:

INTERVENTION COUNTY - HOMA BAY:

  • Homa Bay Mainland (n=approximately 40,000 patients treated): Sequential deployment with 8-month cycling using crowding-out approach: Baseline (AL) → DHA-PIP (8 months) → AS+AQ (8 months) → AL (8 months)
  • Mfangano Island (n=approximately 21,000 patients treated): Extended single MFT deployment: Baseline (AL) → AS+PYD (39 months). This extension allowed longer follow-up surveillance of the most recent combination ACT in Kenya where data was not previously monitored.

COMPARISON COUNTY - MIGORI:

  • Continued artemether-lumefantrine (AL) monotherapy throughout study period (n=32,835 patients treated) PARTICIPANTS: Adults and children ≥5 years diagnosed with uncomplicated Plasmodium falciparum malaria at participating health facilities. Excluded: pregnant women and children <5 years due to medication restrictions and lack of pediatric formulations.

OUTCOMES MEASURED:

Primary Outcomes (reported in Cole et al., Malaria Journal 2024):

  1. Health systems feasibility was assessed through commodity management, human resources adequacy, information system functionality, and implementation barriers/facilitators analysis
  2. Economic costs of MFT deployment including start-up and implementation phases, calculated per facility and per patient were sought after
  3. Stakeholder acceptability among policymakers, healthcare workers, and patients assessed through key informant interviews and surveys was analyzed.

Secondary Outcomes (reported in companion manuscript recently submitted for peer-review):

  1. Prevalence of antimalarial resistance markers in dhfr (N51I, C59R, S108N, I164L), dhps (S436H, A437G, K540E, A581G), mdr1 (N86Y, Y184F), and k13 (A578S, A675V) genes
  2. Temporal trends in resistance marker prevalence over four timepoints (September 2020, August-October 2021, May-July 2022, November 2023-January 2024)
  3. Geographic distribution of resistance patterns across study sites
  4. Complexity of infection (COI) determined by molecular methods

METHODS:

  • Sample collection: Dried blood spots (n=310) from malaria-positive patients at four timepoints
  • Molecular analysis: Targeted amplicon deep sequencing using Oxford Nanopore Technology
  • Health systems assessment: Semi-structured questionnaires, key informant interviews, exit interviews, cost analysis using activity-based costing
  • Statistical analysis: Chi-square tests, Cochran-Armitage trend tests, machine learning models for resistance prediction SETTING: Government and faith-based health facilities in Homa Bay County facilities received MFTs and Migori County (control) where AL was the only ACT used in Western Kenya, a malaria-endemic region with high transmission intensity.

ETHICAL APPROVAL: Strathmore University Institutional Scientific and Ethics Review Committee (SU-ISERC 1730/20) and Kenya National Commission for Science, Technology and Innovation (NACOSTI).

Being tested
Artemether + Lumefantrine, Dihydroartemisin-piperaquine, Artesunate-Amodiaquine (AS-AQ), Pyronaridine - artesunate
Keywords
malaria, Drug Resistance, Multiple first-line therapies, Plasmodium falciparum, Molecular surveillance
Medical subject headings
Malaria, Falciparum, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Artemether + LumefantrineDrug

    Fixed-dose artemisinin-based combination therapy containing artemether and lumefantrine with dosage calculated by weight-bands according to manufacturers recommendations. Administered orally twice daily for 3 days (6 doses total). Used as baseline treatment across all study arms and continued throughout study period in comparison county. First-line treatment for uncomplicated malaria in Kenya. Supplied by Kenya Medical Supplies Authority through routine government procurement.

  • Dihydroartemisin-piperaquineDrug

    Fixed-dose artemisinin-based combination therapy containing dihydroartemisinin and piperaquine with dosage calculated by weight-bands according to manufacturers recommendations. Administered orally once daily for 3 days (3 doses total). Deployed in Homa Bay Mainland for 8 months during adaptive cycling. Donated by Tridem Pharma Ltd through Tridem Pharma Kenya. WHO-recommended ACT for uncomplicated falciparum malaria.

  • Artesunate-Amodiaquine (AS-AQ)Drug

    Fixed-dose artemisinin-based combination therapy. Administered orally once daily for 3 days (3 doses total) with dosage calculated by weighted-bands according to manufacturers recommendations. Deployed in Homa Bay Mainland for 8 months during adaptive cycling following DHA-PIP deployment. Donated by Sanofi through Surgi Pharm Ltd Kenya. WHO-recommended ACT for uncomplicated falciparum malaria.

  • Pyronaridine - artesunateDrug

    Fixed-dose artemisinin-based combination therapy containing pyronaridine and artesunate (granule formulation) with dosage calculated by weighted-bands according to manufacturers recommendations. Administered orally once daily for 3 days (3 doses total). Deployed in Mfangano Island for extended 39-month period. Donated by Shin Poong Pharmaceuticals Co. Ltd, Republic of South Korea. WHO-recommended ACT for uncomplicated falciparum malaria, registered in Kenya but not yet included in national treatment guidelines at time of study hence the need for an extended observational follow-up period.

Study groups in NCT07362498
Study groupRoleWhat they receive
Homa Bay Mainland: MFT Adaptive CyclingSequential deployment of multiple first-line artemisinin-based combination therapies using 8-month adaptive cycling with crowding-out approach. Treatment sequence: Baseline artemether-lumefantrine (AL) followed by dihydroartemisinin-piperaquine (DHA-PIP) for 8 months, then artesunate-amodiaquine (AS+AQ) for 8 months, then return to AL for 8 months. Approximately 40,000 patients treated across multiple health facilities. Note: This observational molecular surveillance study analyzed resistance markers from samples collected during MFT deployment by health authorities (described in Reference 34). Arms represent different drug deployment contexts in which molecular surveillance was conducted. No intervention by research team; observational analysis only.
Receives: Drug: Artemether + Lumefantrine; Drug: Dihydroartemisin-piperaquine; Drug: Artesunate-Amodiaquine (AS-AQ)
Mfangano Island: MFT Extended DeploymentExtended deployment of a single alternative artemisinin-based combination therapy in a geographically isolated island setting. Treatment sequence: Baseline artemether-lumefantrine (AL) followed by pyronaridine-artesunate (AS+PYD) for extended 39-month period. Approximately 21,000 patients treated. This arm assessed health systems feasibility and molecular resistance dynamics with prolonged single MFT deployment in a relatively closed transmission environment since minimal data was available owing to AS+PYD recency of formulary inclusion. Note: This observational molecular surveillance study analyzed resistance markers from samples collected during MFT deployment by health authorities (described in Reference 34). Arms represent different drug deployment contexts in which molecular surveillance was conducted. No intervention by research team; observational analysis only.
Receives: Drug: Artemether + Lumefantrine; Drug: Pyronaridine - artesunate
Migori: ControlContinued artemether-lumefantrine (AL) as the only ACT throughout the entire study period as per Kenya national malaria treatment guidelines. Served as comparison group for health systems outcomes and molecular resistance surveillance. Approximately 32,835 patients treated. This arm represents standard of care without MFT intervention. Note: This observational molecular surveillance study analyzed resistance markers from samples collected during MFT deployment by health authorities (described in Reference 34). Arms represent different drug deployment contexts in which molecular surveillance was conducted. No intervention by research team; observational analysis only.
Receives: Drug: Artemether + Lumefantrine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Health Systems Feasibility - Commodity Management Score

    Assessment of drug supply chain functionality including quantification accuracy, stock management, and distribution logistics. Measured using structured health facility assessment checklist scoring five domains: (1) drug availability, (2) stock-out frequency, (3) quantification accuracy, (4) storage conditions, (5) distribution timeliness. Score range 0-100 where higher scores indicate better commodity management. Assessed at 28 health facilities.

    Measured: June 2020 to January 2024

  2. Health Systems Feasibility - Human Resources and Information Systems Score

    Assessment of human resources adequacy and health information system functionality. Measured using structured facility assessment scoring: (1) healthcare worker availability, (2) training completion rates, (3) reporting tool adoption, (4) KHIS2 system functionality. Score range 0-100 where higher scores indicate better health systems capacity. Assessed at 28 health facilities.

    Measured: June 2020 to January 2024

  3. Stakeholder Acceptability - Composite Acceptability Score

    Composite measure of MFT deployment acceptability among three stakeholder groups: policymakers, healthcare workers, and patients. Measured through: (1) key informant interviews (n=85) using semi-structured guides rated on 5-point Likert scale, (2) patient exit interviews assessing treatment satisfaction (5-point scale), (3) healthcare worker surveys assessing implementation feasibility (5-point scale). Composite score calculated as mean across all stakeholder groups. Range 1-5 where higher scores indicate greater acceptability.

    Measured: June 2020 - January 2024

  4. Economic Costs of Multiple First-Line Treatment Implementation

    Total economic costs of MFT deployment calculated using activity-based costing approach with ingredient method. Includes start-up phase costs (training, IEC materials, reporting tool revision, KHIS2 updates, sensitization) and implementation phase costs (drug procurement, distribution, refresher training, quantification). Costs tracked prospectively from documents, receipts, and market prices. Reported as: (1) total economic vs financial costs in USD, (2) costs by category, (3) costs by funding source, (4) unit cost per facility covered in USD, (5) unit cost per patient treated in USD. Start-up costs annualized over 3-year useful life at 3% discount rate.

    Measured: June 2020 to January 2024

Secondary outcomes (4)
  1. Prevalence of Antimalarial Resistance Markers

    Frequency of known resistance-associated mutations measured as percentage allele frequency (%) for all markers.

    Assessed in four Plasmodium falciparum genes: (1) dhfr - dihydrofolate reductase (codons N51I, C59R, S108N, I164L), (2) dhps - dihydropteroate synthase (codons S436H, A437G, K540E, A581G), (3) mdr1 - multidrug resistance protein 1 (codons N86Y, Y184F), and (4) k13 - kelch13 propeller domain (codons A578S, A675V).

    Determined by targeted amplicon deep sequencing of dried blood spots (n=310) using Oxford Nanopore Technology. Allele frequencies calculated as percentage of reads supporting each allele (range 0-100%). Infections classified as wild-type, mutant, or mixed. Haplotype frequencies determined from microhaplotype analysis.

    Measured: September 2020 to January 2024

  2. Change in Antimalarial Resistance Marker Prevalence Over Time (Cochran-Armitage Trend Test)

    Change in resistance marker prevalence measured as percentage point difference between timepoints, with statistical significance assessed using Cochran-Armitage test for trend.

    Measured over four serial cross-sectional timepoints: T1 (September 2020, baseline when AL used at all sites), T2 (August-October 2021, during MFT deployment), T3 (May-July 2022, continued MFT deployment), T4 (November 2023-January 2024, extended follow-up Mfangano Island only).

    Primary measurement: percentage point change in allele frequency from T1 to T3 (all sites, n=240 balanced comparison). Secondary measurement: percentage point change T1 to T4 (Mfangano Island only, n=111 extended surveillance). Statistical significance determined using Cochran-Armitage test for trend (P<0.05 significant). Assessed separately for each individual mutation and for combined haplotypes.

    Measured: Four time-points over 40 months: T1 (September 2020), T2 (August - October 2021), T3 (May - July 2022), T4 (November 2023 - January 2024)

  3. Geographic Distribution of Antimalarial Resistance Markers

    Comparison of resistance marker prevalence across three geographic study areas: (1) Homa Bay Mainland (intervention with 8-month adaptive cycling), (2) Mfangano Island (intervention with extended single MFT), and (3) Migori County (comparison with continued AL single ACT use). Statistical comparisons using chi-square tests for categorical variables and Fisher's exact tests for intervention vs comparison effects. Analysis accounts for unbalanced sampling design with extended follow-up only for Mfangano Island.

    Measured: September 2020 - January 2024

  4. Complexity of Infection in Plasmodium falciparum

    Mean complexity of infection (COI) defined as the number of genetically distinct parasite clones per infection. Determined using two complementary methods: (1) ama1 genotyping counting maximum number of distinct alleles at polymorphic positions (n=310 samples), and (2) direct haplotype counting from targeted amplicon deep sequencing reads (n=176 samples with sufficient coverage). Infections classified as monoclonal (COI=1) or polyclonal (COI>1). Geographic variation assessed using Kruskal-Wallis test with post-hoc Dunn's test. Results provide context for interpretation of resistance marker data in high-transmission setting.

    Measured: September 2020 - January 2024

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2026
  2. Study start1 Jun 2020
  3. Primary completion31 Jan 2024
  4. Study completion31 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Other
Enrolment
316 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07362498
Sponsor's protocol ID
SU-MFT-2020-001
Other IDs
PO20/00538
Status last verified
Jan 2026
First submitted
1 Jan 2026
Last updated
23 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cole A, Chege T, Aman R, Githuka G, Muga R, Aspinall A, Kokwaro G. Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya. Malar J. 2025 Oct 10;24(1):328. doi: 10.1186/s12936-025-05580-7.

    PubMed 41074071

Questions about this trial

What is this clinical trial studying?

An observational study of Malaria Falciparum, run by Strathmore University at 2 sites in Kenya.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Health Systems Feasibility - Commodity Management Score (time frame: June 2020 to January 2024). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07362498, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.

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