A Study to Find Out if a Combination of 3 Medicines for the Treatment of Malaria Works as Well and is as Safe and Tolerable as Combinations of 2 Medicines
FD-TACT
An Open-label, Randomised, Controlled, Non-inferiority Trial to Compare the Efficacy, Safety and Tolerability of a Fixed Dose Triple Artemisinin-based Combination Therapy (TACT) Artemether-lumefantrine-amodiaquine Versus First-line Artemisinin-based Combination Therapies (ACTs) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria
1 other identifier
interventional
1,680
1 country
1
Brief Summary
The goal of this open-label randomised, controlled, non-inferiority trial is to assess and compare the efficacy, tolerability and safety of a fixed dose TACT artemether-lumefantrine-amodiaquine (ALAQ) to the ACTs artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) (with single low-dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria in patient. The main question it aims to answer is whether ALAQ, a fixed dose TACT, is as efficacious, safe and tolerable in comparison with AL and ASAQ. Participants will be enrolled, admitted and randomised to receive the study drug (ALAQ, AL or ASAQ). Patients will receive directly observed treatments and will be followed up at least once daily for the first 3 days after enrolment followed by weekly visits from D7 up to D42. Patients will be asked to report to the clinics between scheduled visits in case of any illness or other symptoms or complaints.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2025
Shorter than P25 for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 19, 2023
CompletedFirst Posted
Study publicly available on registry
July 19, 2023
CompletedStudy Start
First participant enrolled
September 11, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2026
November 18, 2025
October 1, 2025
11 months
June 19, 2023
November 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
28-day efficacy
28-day efficacy defined as the proportion of patients with Polymerase Chain Reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) at Day 28, i.e., absence up to Day 28 of P. falciparum parasitaemia (detected by microscopy) with parasites genetically identical to those detected at baseline (as determined by PCR product length polymorphisms)
28 days
Secondary Outcomes (18)
28-day PCR uncorrected efficacy
28 days
42-day efficacy
42 days
42-day PCR-uncorrected efficacy
42 days
Parasite clearance half-life
3 days
Proportion of participants with microscopically detectable P. falciparum parasitaemia at Day 3
3 days
- +13 more secondary outcomes
Other Outcomes (15)
Comparison of 28-day PCR-corrected efficacy of ALAQ vs AL
28 days
Comparison of 28-day PCR-uncorrected efficacy of ALAQ vs AL
28 days
Comparison of 42-day PCR-corrected efficacy of ALAQ vs AL
42 days
- +12 more other outcomes
Study Arms (3)
Artemether-Lumefantrine-Amodiaquine (ALAQ)
EXPERIMENTALTACT group
Artemether-Lumefantrine (AL)
ACTIVE COMPARATORACT 1 group
Artesunate-Amodiaquine (ASAQ)
ACTIVE COMPARATORACT 2 group
Interventions
A new fixed-dose combination containing artemether, lumefantrine and amodiaquine (ALAQ) will be used in the trial. Each paediatric (dispersible) tablet will contain 20 mg artemether, 120 mg lumefantrine, 40 mg amodiaquine. Two formulations of (non-dispersible/hard) tablets, containing 50 mg or 60 mg artemether, 300 or 360 mg lumefantrine and 100 or 120 mg amodiaquine, will be used for adolescents or adults. The treatments will be administered in 6 doses over 3 days at H0, H8, H24, H36, H48 and H60. The target dosing will be in line with the ranges recommended by the WHO (total dose of 5-24 mg/kg of artemether, 29-144 mg/ kg of lumefantrine, 22.5-45 mg/kg of amodiaquine).
A fixed-dose combination of AL will be used in the trial. Each paediatric (dispersible or non-dispersible) tablet will contain 20 mg artemether, 120 mg lumefantrine and adult (non-dispersible) tablets will contain 80 mg artemether, 480 mg lumefantrine. Treatment doses will be administered in 6 doses over 3 days at H0, H8, H24, H36, H48 and H60. The target dosing will be in line with the ranges recommended by the WHO.
ASAQ will also be administered as a fixed dose combination. The tablets will contain 25 mg of artesunate and 67.5 mg of amodiaquine in the paediatric formulation and 100 mg artesunate, 270 mg amodiaquine in the adult formulation. The dosing will be administered once a day for 3 days at H0, H24 and H48 according to the schedule currently recommended by the WHO.
Eligibility Criteria
You may qualify if:
- Male or female, aged ≥6 months (no upper limit unless one is required by local regulations) and bodyweight ≥5 kg
- Ability to take oral medication
- Fever defined as ≥38°C tympanic temperature or a history of fever within the last 24 hours
- Acute uncomplicated P. falciparum monoinfection
- Asexual P. falciparum parasitaemia: 1,000/µL to 250,000/µL determined on a peripheral blood film
- Written informed consent by the participant, or by the parent/guardian in case of children lower than the age of consent, and assent if required (per local regulations)
- Willingness and ability of the participants or parents/guardians to comply with the study protocol for the duration of the study
You may not qualify if:
- Signs of severe malaria (adapted from WHO criteria)
- Patients not fulfilling criteria for severe malaria but with other indication(s) for parenteral antimalarial treatment at the discretion of the treating physician
- Haemoglobin \<7 g/dL at screening
- Participants who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days
- In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 30 days
- Acute illness other than malaria requiring systemic treatment
- Severe acute malnutrition
- Known HIV, tuberculosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other severe infection
- For women of child-bearing age: pregnant, trying to get pregnant or lactating
- History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy
- Previous splenectomy
- Participation in the previous 3 months and/or ongoing follow-up for an interventional study (including FD-TACT)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ruhuha Health Centre
Ruhuha, Eastern Province, Rwanda
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mehul Dhorda, Ph.D
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- PRINCIPAL INVESTIGATOR
Arjen Dondorp, Prof.
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 19, 2023
First Posted
July 19, 2023
Study Start
September 11, 2025
Primary Completion (Estimated)
July 31, 2026
Study Completion (Estimated)
July 31, 2026
Last Updated
November 18, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- After completion of the trial activities and reporting
- Access Criteria
- MORU data sharing policy
With participant's consent, participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the Mahidol Oxford Tropical Medicine Research Unit (MORU) data sharing policy with other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records or through interviews.