A Trial to Compare the Efficacy, Safety and Tolerability of Combinations of 3 Anti-malarial Drugs Against Combina-tions of 2 Anti-malarial Drugs.

Last updated: November 14, 2025
Sponsor: University of Oxford
Overall Status: Completed

Phase

3

Condition

N/A

Treatment

Artemether-lumefantrine+ Amodiaquine (AL+AQ)

Artesunate-mefloquine+piperaquine (AS-MQ+PPQ)

Artesunate-mefloquine+placebo (AS-MQ+PBO)

Clinical Study ID

NCT03923725
MAL18004
  • Ages 6-12
  • All Genders

Study Summary

A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine+amodiaquine (AL+AQ) and artesunate-mefloquine+piperaquine (ASMQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (ASMQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Male or female, aged ≥6 months to <12 years (For Gambia, Rwanda sites only: ≥6months)

  • Ability to take oral medication

  • Acute uncomplicated P. falciparum monoinfection

  • Asexual P. falciparum parasitaemia: 1,000/µL to ≤10% parasitaemia, determined on aperipheral blood film (At Gambia, Rwanda sites only: For subjects ≥12 years - 1000/µL to 200,000/µL)

  • Fever defined as ≥ 37.5°C tympanic temperature or a history of fever within the last 24 hours

  • Written informed consent by the subject or by parent/guardian in case of childrenlower than the age of consent and assent if required (per local regulations)

  • Willingness and ability of the subjects or parents/guardians to comply with thestudy protocol for the duration of the study

Exclusion

Exclusion Criteria:

  • Signs of severe malaria (adapted from WHO criteria)

  • Patients not fulfilling criteria for severe malaria but with another indication forparenteral antimalarial treatment at the discretion of the treating physician

  • Haematocrit <15% at screening (For Gambia, Rwanda sites only: For subjects ≥12 years

  • Haematocrit <20% at screening)

  • Subjects who have received artemisinin or a derivative within the previous 7 days ORlumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquinewithin the previous 30 days

  • In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within thelast 14 days.

  • Acute illness other than malaria requiring systemic treatment

  • Severe acute malnutrition (in Niger only - only those patients with Severe AcuteMalnutrition and complications requiring inpatient nutritional treatment will beexcluded)

  • Known HIV infection

  • Known tuberculosis infection

  • For females: post-menarche (For Gambia, Rwanda sites only: females who are pregnant,trying to get pregnant or are lactating)

  • History of allergy or known contraindication to any of the study drugs, includingneuropsychiatric disorders and epilepsy

  • Previous splenectomy

  • Enrolment in DeTACT in the previous 3 months

  • Participation in another interventional study in the previous 3 months

Study Design

Total Participants: 2583
Treatment Group(s): 4
Primary Treatment: Artemether-lumefantrine+ Amodiaquine (AL+AQ)
Phase: 3
Study Start date:
September 01, 2020
Estimated Completion Date:
March 15, 2024

Study Description

Subjects will be randomized to up to four arms: artemether-lumefantrine + amodiaquine, artemether-lumefantrine + placebo, artesunate-mefloquine + piperaquine and artesunate-mefloquine + placebo. As a contingency measure in case of significant differences in the efficacy or safety of one of the combinations being tested and/or study drug expiry or unavailability, subjects may be randomised to 2 arms with a matching ACT-TACT pair, i.e., with artemether-lumefantrine + placebo or artemether-lumefantrine + amodiaquine OR artesunate-mefloquine + placebo or artesunate-mefloquine + piperaquine.

Some sites may randomize between 2 arms only with matching ACT-TACT pairs, i.e., artemether-lumefantrine + placebo or artemether-lumefantrine + amodiaquine OR artesunate-mefloquine + placebo or artesunate-mefloquine + piperaquine. In Rwanda, subjects will be randomized between 2 arms consisting of artemether-lumefantrine + placebo or artemether-lumefantrine + amodiaquine.

In the control arms, the ACT will be co-packed with a matched (appearance) placebo.

In lower transmission settings (Annual Parasite Incidence <50 per 1000 population per year) the treatment will include a single 0.25 mg/kg gametocytocidal dose of primaquine as recommended by the WHO for children ≥10 kg. All drug administrations will be observed.

Subjects will be treated in an in-patient unit for 3 days and followed up weekly up to D63. Microscopy to detect and quantify malaria parasitaemia will be performed daily (more frequently in patients with parasite density of >5000/µL at inclusion) during hospitalization, at all weekly and unscheduled visits. A physical examination and measurements of vital signs along with a symptom questionnaire for tolerability will be performed and recorded through a standardized method at baseline, daily during admission and weekly during follow up through D42 and at all unscheduled visits. Physical exam, vital sign measurements and assessments of symptoms will be performed on D49, D56, and D63 only for patients who are parasitaemic or those who report fever or other symptoms. Electrocardiographs will be performed during admission (H0, H4, H52 or H64) and day 42 of follow up to assess and compare the effect of ACTs and TACTs antimalarials on QT or QTc intervals.

The DeTACT-Africa Trial is funded by UK Aid from the UK government's Foreign, Commonwealth and Development Office.

Connect with a study center

  • Institut des Sciences et Techniques (INSTech)

    Bobo-Dioulasso 2362344,
    Burkina Faso

    Site Not Available

  • Institut des Sciences et Techniques (INSTech)

    Bobo-Dioulasso 01,
    Burkina Faso

    Site Not Available

  • Kinshasa School of Public Health

    Kinshasa, BP 11850 Kin
    Congo, The Democratic Republic of the

    Site Not Available

  • Kinshasa School of Public Health

    Kinshasa 2314302, BP 11850 Kin
    Democratic Republic of the Congo

    Site Not Available

  • MRC Unit The Gambia at LSHTM

    Fajara, Banjul 273
    Gambia

    Site Not Available

  • Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah

    Conakry, B.P. 2649
    Guinea

    Site Not Available

  • Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah

    Conakry 2422465, B.P. 2649
    Guinea

    Site Not Available

  • Epicentre Niger

    Niamey, BP: 13 330
    Niger

    Site Not Available

  • Epicentre Niger

    Niamey 2440485, BP: 13 330
    Niger

    Site Not Available

  • Centre for Malaria and Other Tropical Diseases (CEMTROD)

    Ilorin, Kwara State 1459
    Nigeria

    Site Not Available

  • Centre for Malaria and Other Tropical Diseases (CEMTROD)

    Ilorin 2337639, Kwara State 2332785 1459
    Nigeria

    Site Not Available

  • College of Medicine and Health Sciences, University of Rwanda

    Kigali,
    Rwanda

    Site Not Available

  • College of Medicine and Health Sciences, University of Rwanda

    Kigali 202061,
    Rwanda

    Site Not Available

  • National Institute For Medical Research (NIMR), Tanga Medical Research Centre

    Tanga,
    Tanzania

    Site Not Available

  • National Institute For Medical Research (NIMR), Tanga Medical Research Centre

    Tanga 149606,
    Tanzania

    Site Not Available

  • MRC Unit The Gambia at LSHTM

    Fajara 2413527, City of Banjul 2413875 273
    The Gambia

    Site Not Available

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