Malaria
Conditions
Interventions
Artemether Lumefantrine
Artemether Lumefantrine Amodiaquine
Artesunate Mefloquine Piperaquine
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female, aged =6 months to <12 years (For Gambia, Rwanda sites only: =6 months) • Ability to take oral medication • Acute uncomplicated P. falciparum monoinfection • Asexual P. falciparum parasitaemia: 1,000/µL to =10% parasitaemia, determined on a peripheral 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 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 subjects or parents/guardians to comply with the study protocol for the duration of the study
Exclusion criteria
Exclusion criteria: ?Signs of severe malaria (adapted from WHO criteria) ?Patients not fulfilling criteria for severe malaria but with another indication for parenteral 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 OR lumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquine within the previous 30 days ?In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 14 days. ?Acute illness other than malaria requiring systemic treatment; ?Severe acute malnutrition (in Niger only – only those patients with Severe Acute Malnutrition and complications requiring inpatient nutritional treatment will be excluded) ?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, including neuropsychiatric disorders and epilepsy ?Previous splenectomy ?Enrolment in DeTACT in the previous 3 months ?Participation in another interventional study in the previous 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 42-day efficacy defined as PCR-corrected adequate clinical and parasitological response (ACPR). | — |
Secondary
| Measure | Time frame |
|---|---|
| For safety and tolerability: Incidence of adverse events and serious adverse events within the first 42 days including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity, in particular QT or QTc-interval above 500 ms at timepoint H4 and H52/H64 and between these time points; change in haemoglobin concentration at day 3, 7, 28, stratified for G6PD status/genotype; proportion of subjects requiring retreatment due to vomiting within 1 hour after administration of the study drugs; 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 ;For efficacy: 63-day PCR corrected and uncorrected efficacy; 42-day PCR uncorrected efficacy; parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance; proportion of subjects with microscopically detectable P. falciparum parasitaemia at Day 3; fever clearance time (i.e. the time taken for the tympanic temperature to fall below 37.5 ºC in patients who were febrile at inclusion); proportion of subjects with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment. ;For PK/PD interactions: Pharmacokinetic profiles and 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; day 7 plasma levels of partner drugs in correlation with treatment efficacy and treatment arm | — |
Countries
Burkina Faso, Democratic Republic of the Congo, Gambia, Guinea, Niger, Nigeria, Rwanda, Tanzania
Contacts
Public ContactMehul Dhorda
Project Coordinator
Outcome results
None listed