Fixed-dose combination of artemether-lumefantrine-amodiaquine for uncomplicated falciparum malaria
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
This trial will test whether a single fixed-dose combination of three antimalarials (artemether-lumefantrine-amodiaquine) works as well and is as safe and tolerable as standard two-drug combinations for people with uncomplicated Plasmodium falciparum malaria.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 1680 (estimated) |
| Ages | 6 Months and up |
| Sex | All |
| Sponsor | University of Oxford Academic / other |
| Locations | 1 site (Ruhuha, Eastern Province) |
| Trial ID | NCT05951595 on ClinicalTrials.gov |
What this trial studies
This is an open-label, randomized, controlled non-inferiority Phase 3 trial comparing a fixed-dose triple artemisinin-based combination (ALAQ) with two standard two-drug ACTs (artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Eligible participants (aged ≥6 months and ≥5 kg) with uncomplicated P. falciparum infection are admitted for three days for directly observed oral treatment and daily parasitemia monitoring, then followed weekly to day 42. The overall sample size is 1,680 with a 2:1:1 randomization (840 ALAQ, 420 AL, 420 ASAQ) across African and Asian sites, and microscopy and parasite clearance assessments are performed frequently during hospitalization and follow-up. In lower-transmission settings a single low dose of primaquine may be given per WHO guidance where local policy allows.
Who should consider this trial
Good fit: Ideal candidates are people aged six months or older (≥5 kg) with acute uncomplicated P. falciparum monoinfection and parasite densities between 1,000 and 250,000/µL who can take oral medication and comply with a three-day inpatient period plus follow-up to day 42.
Not a fit: Patients with signs of severe malaria, indications for parenteral antimalarial therapy, haemoglobin below 7 g/dL, mixed infections, or inability to take oral medications are unlikely to be eligible or to benefit from this comparison.
Why it matters
Potential benefit: If successful, the triple fixed-dose combination could provide similarly effective treatment while being more resilient to emerging partner-drug resistance and help prolong the usefulness of artemisinin-based therapies.
How similar studies have performed: Previous clinical work on triple artemisinin-based combinations has shown promising results in areas with partner-drug resistance, but fixed-dose TACTs remain under evaluation in larger Phase 3 trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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)
Where this trial is running
Ruhuha, Eastern Province
- Ruhuha Health Centre — Ruhuha, Eastern Province, Rwanda (Recruiting)
Study contacts
- Principal investigator: Mehul Dhorda, Ph.D — Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Study coordinator: Mehul Dhorda, Ph.D
- Email: mehul@tropmedres.ac
- Phone: +66 2 203-6333
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.