Malaria, Falciparum Clinical Trial
Official title:
Artemisinin Resistance in Cambodia
The principal aim of this project is to investigate reports of developing artemisinin resistance in Cambodia using an integrated in vivo - in vitro approach to examine recent alarming reports of treatment failures with advanced combination therapies along the Thai-Cambodian border, which could have major impact on the malaria situation in the affected areas as well as the rest of the malaria-endemic world.
A total number of 90 volunteers with acute uncomplicated falciparum malaria will be randomly
assigned to be treated with either artesunate monotherapy for 7 days or the combination of
quinine and tetracycline over 7 days (following the 2nd line national treatment guideline of
the national malaria control program) at a ratio of 2:1. The study design will be based on
the WHO recommendations for the 'Assessment and Monitoring of Antimalarial Drug Efficacy for
the Treatment of Uncomplicated Falciparum Malaria' (WHO, 2003). Study participants will be
otherwise healthy malaria patients (adult men and non-pregnant women aged 18 to 65 years)
with uncomplicated falciparum malaria recruited in Battambong Province, Cambodia.
The artesunate will be administered orally (a single dose of 200 mg per day) over a total
duration of 7 days (Directly Observed Therapy). Quinine (30 mg/kg/day) plus tetracycline (25
mg/kg/day) will also be administered over 7 days in split dose every 8 hours following the
national treatment guidelines of Cambodia.
Patients will be admitted to the hospital for the duration of study drug administration or
until all signs and symptoms of malaria have disappeared, whichever comes first. Thereafter
until Day 21 patients have to remain in a malaria-free environment (such as Sampov Luon or
Ta Sanh) either in the hospital or in a living facility provided at the study site where the
patients will be supervised by study personnel. After Day 21 they will be followed as
outpatients until Day 28 with a scheduled follow-up visit on Day 28.
In vitro drug sensitivity assays will be performed from samples on inclusion and in case of
recrudescence. Drug levels will be measured in the artesunate arm on the first and last day
of therapy.
Primary clinical outcome is cure (Adequate Clinical and Parasitological Response - ACPR) on
Day 28. Secondary outcome measures are time until parasite, fever, and gametocyte clearance
(PCT, FCT, and GCT). Parasite genotyping will be used to distinguish recrudescences from
reinfections by PCR. Subjects will be monitored for clinical adverse events throughout the
study duration.
Blood will be drawn on the day of admission (before initiating therapy) for in vitro drug
sensitivity testing and for PCR (markers of drug resistance and to distinguish recrudescence
from reinfection by genotyping). Malaria smears will be prepared up to 4 times a day until
parasite clearance and on Days 7, 14, 21, and 28 or whenever symptoms consistent with
malaria appear. Plasma samples for determining drug levels will be obtained on the first and
last day of therapy. Over the entire study, up to approximately 64 ml of blood may be drawn
by venipuncture. Study participation for each individual will be 28 days.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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