A Study by the Tracking Resistance to Artemisinin Collaboration (TRAC) (TRACII)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02453308|
Recruitment Status : Completed
First Posted : May 25, 2015
Last Update Posted : May 9, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Malaria, Falciparum||Drug: ACT Drug: TACT||Phase 2 Phase 3|
In Laos, Myanmar, Bangladesh, India and DRC, the following two combinations will be used:
- Artemether-lumefantrine combined with amodiaquine (TACT arm) or
- Artemether-lumefantrine (ACT arm)
In Myanmar and Vietnam the following two combinations will be used:
- Dihydroartemisinin-piperaquine combined with mefloquine (TACT arm) or
- Dihydroartemisinin-piperaquine (ACT arm)
In Cambodia and Thailand the following two combinations will be used:
- Dihydroartemisinin-piperaquine plus Mefloquine hydrochloride (TACT arm) or
- Artesunate-mefloquine (ACT arm)
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-centre, Open-label Randomised Trial to Assess the Efficacy, Safety and Tolerability of Triple Artemisinin-based Combination Therapies (TACTs) Com-pared to Artemisinin-based Combination Therapies (ACTs) in Uncomplicated Falciparum Malaria and to Map the Geographical Spread of Artemisinin and Partner Drug Resistance|
|Actual Study Start Date :||August 2015|
|Actual Primary Completion Date :||March 2018|
|Actual Study Completion Date :||March 2018|
Active Comparator: ACT-arms
1.1 Artemether-lumefantrine for 3 days.
1.2 Dihydroartemisinin-piperaquine for 3 days
1.3 Artesunate-Mefloquine for 3 days
Active Comparator: TACT-arms
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.
- PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR) [ Time Frame: 42 days ]
- Parasite clearance half-life [ Time Frame: 42 days ]Parasite clearance half-life assessed by microscopy as primary parameter to de-termine parasite clearance
- 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 [ Time Frame: 42 days ]Total billirubin, ALT, AST and Alkaline Phosphatase will be measured
- Incidence of adverse events concerning markersof renal toxicity [ Time Frame: 42 days ]Creatinine will be measured
- Incidence of prolongation of the QTc-interval [ Time Frame: 3 days ]Incidence of prolongation of the Qtc-interval above 500 ms or > 60ms above baseline values
- Change in hemoglobin/hematocrit [ Time Frame: 42 days ]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
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02453308
|Principal Investigator:||Arjen Dondorp, MD||Mahidol Oxford Tropical Medicine Research Unit|