Malaria
Conditions
Interventions
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion 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 by the participant aged >12 years to <18 years (unless local regulations specify a different age group) • Willingness and ability of the participants 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 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, 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-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 H52 or H64; proportion of participants requiring retreatment due to vomiting within 1 hour after administration of the study drugs; proportion of participants who report 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: 28-day PCR uncorrected efficacy, 28-day PCR-corrected and uncorrected efficacy per site, 42-day PCR-corrected and uncorrected efficacy; parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance; proportion of participants 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°C in participants who were febrile at inclusion); proportion of participants with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment.;For PK/PD interactions: Pharmacokinetic profiles and interactions of artemisinin-derivatives and partner drugs in ACT and TACT treated participants in correlation with pharmacodynamics measures of drug efficacy; day 7 plasma levels of partner drugs in correlation with treatment efficacy and treatment arm | — |
Countries
Angola, Nigeria, Rwanda, Thailand, Uganda
Contacts
Public ContactMehul Dhorda
Principal Investigator
Outcome results
None listed