a study by the tracking resistance to artemisinin collaboration (trac)

Conditions: Malaria, Falciparum

Summary: this study is an open-label randomised trial comparing standard act treatment with matching triple artemisinin-based combination therapies (tacts), evaluating efficacy in safety and tolerability. the estimated total sample size is 2040 patients from 16 sites in asia and 1 site in africa. there are 2 arm study groups that have 2 treatment arms each. study group a: a.1: artemether-lumefantrine for 3 days. versus: a.2: artemether-lumefantrine for 3 days plus amodiaquine for 3 days. study group b: b.1: dihydroartemisinin-piperaquine for 3 days. versus: b.2: dihydroartemisinin-piperaquine for 3 days plus mefloquine hydrochloride for 3 days. study group c: c.1: artesunate-mefloquine for 3 days versus: c.2: dihydroartemisinin-piperaquine for 3 days plus mefloquine hydrochloride for 3 days. according to the who guideline, all patients except for children under the age of 1 year or a weight below 10 kilograms will also be treated with a single dose of low dose primaquine.

in laos, myanmar, bangladesh, india and drc, the following two combinations will be used: 1. artemether-lumefantrine combined with amodiaquine (tact arm) or 2. artemether-lumefantrine (act arm) in myanmar and vietnam the following two combinations will be used: 1. dihydroartemisinin-piperaquine combined with mefloquine (tact arm) or 2. dihydroartemisinin-piperaquine (act arm) in cambodia and thailand the following two combinations will be used: 1. dihydroartemisinin-piperaquine plus mefloquine hydrochloride (tact arm) or 2. artesunate-mefloquine (act arm)

Eligibility criteria:
inclusion criteria: * male or female, aged from 6 months to 65 years old * acute uncomplicated p. falciparum malaria, confirmed by positive blood smear with asexual forms of p. falciparum (or mixed with non-falciparum species) * asexual p. falciparum parasitaemia: 5,000 to 200,000/ul, de-termined on a thin or thick blood film (in cambodia patients with a parasitaemia of 16 to 200,000/ul are eligible. in drc patients with a parasitaemia of 10,000 to 250,000/ul are eligi-ble) * fever defined as \>/= 37.5°c tympanic temperature or a history of fever within the last 24 hours * written informed consent (by parent/guardian in case of children) * willingness and ability of the patients or parents/guardians to comply with the study protocol for the duration of the study exclusion criteria: * signs of severe/complicated malaria * haematocrit \< 25% or hb \< 5 g/dl at screening (drc: hct\<15% and hb \<5 g/dl due to high prevalence of anemia). * acute illness other than malaria requiring treatment * for females: pregnancy, breast feeding * patients who have received artemisinin or a derivative or an artemisinin containing combination therapy (act) within the previous 7 days * treatment with mefloquine in the 2 months prior to presentation will be an exclusion criteria in the dha-p+mq sites * history of allergy or known contraindication to artemisinins, or to the act or tact to be used at the site e.g. neuropsychiatric disorders will be a contraindication for the use of mefloquine. * previous splenectomy * qtc-interval \> 450 milliseconds at moment of presentation * documented or claimed history of cardiac conduction problems * earlier participation within the tracii trial or another trial in the previous 3 months.

Keywords: artemisinin combination therapies