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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02453308
• Date of registration: 20/04/2015
• Prospective Registration: Yes
• Primary sponsor: University of Oxford
• Public title: A Study by the Tracking Resistance to Artemisinin Collaboration (TRAC) TRACII
• Scientific 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
• Date of first enrolment: August 2015
• Target sample size: 1110
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02453308
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Bangladesh, Cambodia, Congo, The Democratic Republic of the, India, Lao People's Democratic Republic, Myanmar, Thailand, Vietnam

Contacts

• Name: Arjen Dondorp, MD
• Affiliation: Mahidol Oxford Tropical Medicine Research Unit (MORU)

Key inclusion & exclusion 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.



Age minimum: 6 Months
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Malaria, Falciparum

Intervention(s)

Drug: TACT

Drug: ACT

Primary Outcome(s)

PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR) [Time Frame: 42 days]

Secondary Outcome(s)

Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics [Time Frame: 14 days]

Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm [Time Frame: Day 7]

Time for parasite count to fall to 90% of initial parasite density [Time Frame: 42 days]

Transcriptomic patterns at t=0 and t=6h comparing sensitive and resistant parasites [Time Frame: 6hrs after start of treatment]

Time for parasite count to fall to 99% of initial parasite density [Time Frame: 42 days]

Fever clearance time [Time Frame: 42 days]

In vitro sensitivity (expressed in IC50 values among others) of P. falciparum to artemisinins and partner drugs [Time Frame: 42 days]

Incidence of adverse events concerning markers of hepatic toxicity [Time Frame: 42 days]

Parasite clearance half-life [Time Frame: 42 days]

Genome wide association with in vivo/in vitro sensitivity parasite phenotype [Time Frame: 42 days]

Change in hemoglobin/hematocrit [Time Frame: 42 days]

Incidence of adverse events and serious adverse events [Time Frame: 42 days]

Time for parasite count to fall to 50% of initial parasite density [Time Frame: 42 days]

Proportion of patients with gametocytemia before,after treatment with Primaquine [Time Frame: assessed at admission, up to day 14]

• 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]

Correlation between SNPs measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples [Time Frame: 42 days]

Incidence of adverse events concerning markersof renal toxicity [Time Frame: 42 days]

Incidence of prolongation of the QTc-interval [Time Frame: 3 days]

Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy [Time Frame: at 24 and 48 hours]

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]

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]

Levels of RNA transcription coding for male or female specific gametocytes [Time Frame: at admission up to day 14]

Secondary ID(s)

BAKMAL1502

Source(s) of Monetary Support

Please refer to primary and secondary sponsors