A Phase 2/3 interventional study of ACT and TACT in Malaria, Falciparum, sponsored by University of Oxford. Completed at 20 sites in 8 countries. Open to participants aged 6 Months to 65 Years. Per ClinicalTrials.gov, last updated 2018-05-09.
Sponsored by University of Oxford · Phase 2/3, Interventional, and Treatment
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:
In Myanmar and Vietnam the following two combinations will be used:
In Cambodia and Thailand the following two combinations will be used:
Exclusion Criteria:
1.1 Artemether-lumefantrine for 3 days. 1.2 Dihydroartemisinin-piperaquine for 3 days 1.3 Artesunate-Mefloquine for 3 days
Drug: ACT
2.1: Artemether-lumefantrine for 3 days.plus: Amodiaquine for 3 days. 2.2: Dihydroartemisinin-piperaquine for 3 days. plus: Mefloquine hydrochloride for 3 days. 2.3 Dihydroartemisinin-piperaquine for 3 days. plus: Mefloquine hydrochloride for 3 days.
Drug: TACT
1. Artemether-lumefantrine for 3 days 2. Dihydroartemisinin-piperaquine for 3 days. 3. Artesunate-mefloquine for 3 days
1. Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. 2. Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days. 3. Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days.
PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR)
Time frame: 42 days
Parasite clearance half-life
Parasite clearance half-life assessed by microscopy as primary parameter to de-termine parasite clearance
Time frame: 42 days
Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy
Time frame: at 24 and 48 hours
Time for parasite count to fall to 50% of initial parasite density
Time frame: 42 days
Time for parasite count to fall to 90% of initial parasite density
Time frame: 42 days
Time for parasite count to fall to 99% of initial parasite density
Time frame: 42 days
Fever clearance time
Time frame: 42 days
Incidence of adverse events and serious adverse events
Time frame: 42 days
Incidence of adverse events concerning markers of hepatic toxicity
Total billirubin, ALT, AST and Alkaline Phosphatase will be measured
Time frame: 42 days
Incidence of adverse events concerning markersof renal toxicity
Creatinine will be measured
Time frame: 42 days
Incidence of prolongation of the QTc-interval
Incidence of prolongation of the Qtc-interval above 500 ms or \> 60ms above baseline values
Time frame: 3 days
Change in hemoglobin/hematocrit
Change in hemoglobin/hematocrit on day 1 to 7, 14, 21, 28, 35 and 42 according to geographical location and study arm, stratified for G6PD status
Time frame: 42 days
Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study
Time frame: 42 days
Prevalence of Kelch13 mutations of known functional significance
Time frame: 42 days
Prevalence/incidence of other genetic markers of antimalarial drug resistance
Time frame: 42 days
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Time frame: 42 days
Correlation between SNPs measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples
Time frame: 42 days
Transcriptomic patterns at t=0 and t=6h comparing sensitive and resistant parasites
Time frame: 6hrs after start of treatment
Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics
Time frame: 14 days
Proportion of patients with gametocytemia before,after treatment with Primaquine
Time frame: assessed at admission, up to day 14
Levels of RNA transcription coding for male or female specific gametocytes
Time frame: at admission up to day 14
In vitro sensitivity (expressed in IC50 values among others) of P. falciparum to artemisinins and partner drugs
Time frame: 42 days
• Pharmacokinetic profiles and interactions of artemisinin-derivatives and partner drugs (half-life, Cmax, AUC, Tmax) in 20 ACT treated and 20 TACT treated patients of both study arms
Time frame: 42 days
Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm
Time frame: Day 7
This study is completed, as verified in May 2018. You cannot join it, but the record below documents what was studied.
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University of Oxford