NCT07362498

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
316

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jun 2020

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2020

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2024

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

January 1, 2026

Completed
22 days until next milestone

First Posted

Study publicly available on registry

January 23, 2026

Completed
Last Updated

January 23, 2026

Status Verified

January 1, 2026

Enrollment Period

3.7 years

First QC Date

January 1, 2026

Last Update Submit

January 15, 2026

Conditions

Malaria Falciparum

Keywords

malariaDrug ResistanceMultiple first-line therapiesPlasmodium falciparumMolecular surveillance

Outcome Measures

Primary Outcomes (4)

  • 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.

    June 2020 to January 2024

  • 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.

    June 2020 to January 2024

  • 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.

    June 2020 - January 2024

  • 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.

    June 2020 to January 2024

Secondary Outcomes (4)

  • Prevalence of Antimalarial Resistance Markers

    September 2020 to January 2024

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

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

  • Geographic Distribution of Antimalarial Resistance Markers

    September 2020 - January 2024

  • Complexity of Infection in Plasmodium falciparum

    September 2020 - January 2024

Study Arms (3)

Homa Bay Mainland: MFT Adaptive Cycling

Sequential 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.

Drug: Artemether + LumefantrineDrug: Dihydroartemisin-piperaquineDrug: Artesunate-Amodiaquine (AS-AQ)

Mfangano Island: MFT Extended Deployment

Extended 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.

Drug: Artemether + LumefantrineDrug: Pyronaridine - artesunate

Migori: Control

Continued 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.

Drug: Artemether + Lumefantrine

Interventions

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.

Homa Bay Mainland: MFT Adaptive CyclingMfangano Island: MFT Extended DeploymentMigori: Control
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.

Homa Bay Mainland: MFT Adaptive Cycling
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.

Homa Bay Mainland: MFT Adaptive Cycling
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.

Mfangano Island: MFT Extended Deployment

Eligibility Criteria

Age5 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
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.

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Homa Bay County Health Facilities

Homa Bay, Homa Bay County, 40300, Kenya

Location

Migori County Teaching and Referral Hospital

Migori, Migori County Kenya, 40400, Kenya

Location

Related Publications (1)

  • 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.

    PMID: 41074071BACKGROUND

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

This observational molecular surveillance study was non-randomized. Multiple first-line therapies (MFTs) were deployed by health authorities as a health systems implementation program (Reference 34). The research team conducted observational molecular analysis only and did not assign treatments. Homa Bay Mainland received 8-month ACT cycling: AL baseline, then DHA-PIP, AS+AQ, and return to AL. Mfangano Island received extended 39-month AS+PYD deployment. Migori County continued AL monotherapy throughout (control). Dried blood spots (DBS) were collected from malaria-positive, de-identified laboratory samples at four time-points: T1 (Sep 2020, AL all sites), T2 (Aug-Oct 2021, DHA+PIP Homa Bay Mainland, AS+PYD 12 months Mfangano), T3 (May-Jul 2022, AS+AQ Homa Bay, AS+PYD Mfangano), T4 (Nov 2023-Jan 2024, Mfangano extended follow-up). Samples were analyzed by targeted amplicon deep sequencing for antimalarial resistance markers in dhfr, dhps, mdr1, and k13 genes.

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

Artemether, Lumefantrine Drug Combinationamodiaquine, artesunate drug combinationpyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Gilbert Kokwaro, PhD, FKNAS, FAAS

    Institute of Healthcare Management, Strathmore University

    STUDY DIRECTOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research Scientist

Study Record Dates

First Submitted

January 1, 2026

First Posted

January 23, 2026

Study Start

June 1, 2020

Primary Completion

January 31, 2024

Study Completion

January 31, 2024

Last Updated

January 23, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

KE(2)