A Phase 3 interventional study of Artemether-lumefantrine+ Amodiaquine (AL+AQ) and Artemether-lumefantrine + placebo (AL+PBO) in Plasmodium Falciparum Malaria (Uncomplicated), sponsored by University of Oxford. Completed at 8 sites in 8 countries. Open to participants aged 6 Months to 12 Years. Per ClinicalTrials.gov, last updated 2025-11-18.
Sponsored by University of Oxford · Phase 3, Interventional, and Treatment
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.
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.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 2,583 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Triple ACTs
Drug: Artemether-lumefantrine+ Amodiaquine (AL+AQ)
ACTs
Drug: Artemether-lumefantrine + placebo (AL+PBO)
Triple ACTs
Drug: Artesunate-mefloquine+piperaquine (AS-MQ+PPQ)
ACTs
Drug: Artesunate-mefloquine+placebo (AS-MQ+PBO)
Drug page: Amodiaquine
AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. AQ: is available as dispersible tablets of 40 mg. The weight-based treatment schedule aims for a dosage of approximately 10mg (4.5-15mg)/kg/day amodiaquine for three days.
AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. PBO: Placebo tablets for amodiaquine are identical in size, shape and color to the amodiaquine tablets.
AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PPQ: Piperaquine will be administered according to an optimised dosing schedule using tablets of 160 or 500 mg of piperaquine tetraphosphate. The weight-based treatment aims for a dosage of approximately. * 24 mg/kg/day in patients \<25 kg (range 16.0 - 32.0 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 20 - 32 mg/kg per day. * 18 mg/kg/day in patients ≥25 kg (range 15.0 - 29.4 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 16 - 27 mg/kg per day.
AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PBO: Placebo tablets for piperaquine are identical in size, shape and colour to the piperaquine tablets.
42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR).
42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR).
Time frame: 42 days
63-day PCR corrected and uncorrected efficacy
Time frame: 63 days
42-day PCR uncorrected efficacy
Time frame: 42 days
Parasite clearance half-life
Assessed by microscopy as primary parameter to determine parasite clearance
Time frame: 3 Days
Proportion of subjects with microscopically detectable P. falciparum parasitaemia
Time frame: Day 3
Fever clearance time
fever clearance time (i.e. the time taken for the tympanic temperature to fall below 37.5 ºC)
Time frame: 63 Days
Proportion of subjects with gametocytaemia
proportion of subjects with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment
Time frame: 63 Days
Incidence of adverse events
including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity
Time frame: 42 days
Incidence of serious adverse events
including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity
Time frame: 42 days
Number of cardiotoxicity events
In particular QT or QTc-interval above 500 ms at timepoint H4 and H52/H64 and between these time points
Time frame: 52 or 64 hours depends on treatment arm
Change in haemoglobin stratified for G6PD status/genotype
Time frame: 28 days
Proportion of subjects requiring retreatment due to vomiting
Proportion of subjects requiring retreatment due to vomiting within 1 hour after administration of the study drugs
Time frame: 1 hour
Proportion of subjects that reports completing a full course of observed TACT
Time frame: 3 days
Proportion of subjects that reports completing a full course of observed ACT
Time frame: 3 days
proportion of subjects that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event.
Time frame: 42 days
Pharmacokinetic profiles
including Cmax and AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated subjects in correlation with pharmacodynamics measures of drug efficacy
Time frame: 42 days
Pharmacokinetic interactions
including Cmax and AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated subjects in correlation with pharmacodynamics measures of drug efficacy
Time frame: 42 days
Plasma levels of partner drugs
Plasma levels of partner drugs in correlation with treatment efficacy and treatment arm
Time frame: 7 days
Comparison of 63-day vs 42-day PCR corrected and uncorrected efficacy
Comparison of 63-day vs 42-day PCR corrected and uncorrected efficacy of ACTs vs TACTs
Time frame: 63 days
Proportions of recurrent infections
Proportions of recurrent infections with parasites carrying mutations of known functional significance
Time frame: 63 days
Proportions of specimens collected at baseline with parasites carrying mutations
Proportions of specimens collected at baseline with parasites carrying mutations of known functional or operational significance (pfkelch13, pfcrt, pfmdr1, pfdhfr, pfdhps, pfplasmepsin2 , partial or complete deletions of pfhrp2 and other current parasite genetic markers associated with resistance or identified over the course of the study)
Time frame: baseline
Candidate markers of resistance
Candidate markers of resistance identified through genome wide association studies with in vivo or in vitro parasite drug sensitivity phenotypes
Time frame: 63 days
In vitro sensitivity of P. falciparum to artemisinins and partner drugs
In vitro sensitivity of P. falciparum to artemisinins and partner drugs according to study sites and genotype
Time frame: 63 days.
Accuracy of SNPs assessment
Accuracy of SNPs assessment from dry blood spots versus from whole genome sequencing in leukocyte depleted blood samples
Time frame: 63 days.
Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics
Time frame: 14 days
Correlation of parasite clearance metrics as assessed by microscopy versus digital microscopy
Time frame: 3 days
Comparison of transcriptomic patterns of drug sensitive and resistant parasites
Comparison of transcriptomic patterns of drug sensitive and resistant parasites before treatment and 6, 12 and 24 hours after start of treatment
Time frame: 63 days
Levels of RNA transcription coding for male or female specific gametocytes
Levels of RNA transcription coding for male or female specific gametocytes at admission up to day 14, stratified by the presence of gametocytes at enrolment
Time frame: 14 days
Correlation between the host genotype and the pharmacokinetics and pharmacodynamics of antimalarials.
Host genotype (e.g., CYP2D6, CYP3A4, KCNQ1/LQT1, KCNH2/LQT2, SCN5A/LQT3)
Time frame: 42 days
Correlations between the place of residence, work, recent travel history
Correlations between the place of residence, work, recent travel history assessed by interview and mobile phone records to identify behaviours and risk factors associated with malaria infection.
Time frame: 63 days
Correlation between titres of antibodies against malaria parasite antigens and - efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR) - efficacy defined as adequate clinical and parasitological response (ACPR)
Time frame: 63 days
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — 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 MORU data sharing policy with data repositories such as the WorldWide Antimalarial Resistance Network (WWARN, terms of submission here: http://www.wwarn.org/tools-resources/terms-submission) or other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records, through interviews, or from mapping data.
Time frame: After completion of trial activities and reporting.
Access criteria: MORU Data Sharing Policy https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing WWARN Terms of Data Access https://www.wwarn.org/tools-resources/terms-data-access
This study is completed, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Amodiaquine