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A Study by the Tracking Resistance to Artemisinin Collaboration (TRAC)

Information source: University of Oxford
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Malaria, Falciparum; Drug Resistance

Intervention: ACT (Drug); TACT (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of Oxford

Overall contact:
Rob van der Pluijm, MD, Phone: +662 203 6333, Email: Rob@tropmedres.ac


This study is an open-label randomised trial comparing standard ACT treatment with matching triple artemisinin-based combination therapies (TACTs), evaluating efficacy in sites experiencing ACT failure and safety, tolerability and artemisinin and partner drug resistance in all sites. The estimated total sample size is 1680 patients which come from 13 sites in Asia and 1 site in Africa. There are 2 arm drugs to compare as follows: Study group A: A. 1: Artemether-lumefantrine for 3 days. or: A. 2: Artemether-lumefantrine for 3 days. plus: Amodiaquine for 3 days. Study group B: B. 1: Dihydroartemisinin-piperaquine for 3 days. or: B. 2: Dihydroartemisinin-piperaquine for 3 days. plus: Mefloquine hydrochloride for 3 days. Primaquine 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 primaquine according to the local requirement and WHO treatments schedule as a gametocytocidal treatment.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: PCR corrected efficacy defined as ACPR

Secondary outcome:

Parasite clearance half-life

Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy

Time for parasite count to fall to 50% of initial parasite density

Time for parasite count to fall to 90% of initial parasite density

Time for parasite count to fall to 99% of initial parasite density

Fever clearance time

Incidence of adverse events and serious adverse events

Incidence of adverse events of hepatic toxicity

Incidence of adverse events of renal toxicity

Incidence of prolongation of the QTc-interval


Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study

Prevalence of Kelch13 mutations of known functional significance

Prevalence/incidence of other genetic markers of antimalarial drug resistance

Genome wide association with in vivo/in vitro sensitivity parasite phenotype

Correlation between SNPs measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples

Transcriptomic patterns comparing sensitive and resistant parasites

Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics

Proportion of patients with gametocytemia before, during and after treatment with TACTs or ACTs

Levels of RNA transcription coding for male or female specific gametocytes

In vitro sensitivity (expressed in IC50 values among others) of P. falciparum to artemisinins and partner drugs

half-life, Cmax, AUC, Tmax

Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm

Detailed description: In Laos, Myanmar, Bangladesh, India and DRC will use the following two combinations: 1. Artemether-lumefantrine combined with amodiaquine (TACT group) or 2. Artemether-lumefantrine (ACT group) In Cambodia, Myanmar, Vietnam and Thailand will use the following two combinations: 1. Dihydroartemisinin-piperaquine combined with mefloquine (TACT group) or 2. Dihydroartemisinin-piperaquine (ACT group)


Minimum age: 6 Months. Maximum age: 65 Years. Gender(s): Both.


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 (see chapter 5)

- Haematocrit < 25% or Hb < 5 g/dL at enrollment (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


Locations and Contacts

Rob van der Pluijm, MD, Phone: +662 203 6333, Email: Rob@tropmedres.ac

College of Medicine Chittagong, Ramu, Bangladesh; Recruiting

Pailin, Pailin, Cambodia; Not yet recruiting

Preah Vihear, Preah Vihear, Cambodia; Not yet recruiting

Pursat, Pursat, Cambodia; Not yet recruiting

Ratanakiri, Ratankiri, Cambodia; Not yet recruiting

Kinshasa, Kinshasa, Congo, The Democratic Republic of the; Not yet recruiting

Attopeu, Attopeu, Lao People's Democratic Republic; Not yet recruiting

Mohanpur Community health center, Agartala, Myanmar; Not yet recruiting

Midnapore, Midnapore, Myanmar; Not yet recruiting

Ispat General hospital, Rourkela, Myanmar; Not yet recruiting

Chumporn hospital, Chumporn, Thailand; Not yet recruiting

Binh Phuoc hospital, Binh Phuoc, Vietnam; Not yet recruiting

Phusing hospital, Phusing, Srisaket, Thailand; Not yet recruiting

Tha Song Yang hospital, Tha Song Yang, Tak, Thailand; Not yet recruiting

Additional Information

Starting date: August 2015
Last updated: August 18, 2015

Page last updated: August 23, 2015

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