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NCT Number: NCT02453308

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

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.

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Key information

Conditions

Malaria, Falciparum Infections Malaria Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

6 month–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

College of Medicine Chittagong, Rāmu, Bangladesh

Loading trial locations.

About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ACT

Drug
  • Artemether-lumefantrine for 3 days
  • Dihydroartemisinin-piperaquine for 3 days.
  • Artesunate-mefloquine for 3 days

TACT

Drug
  • Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days.
  • Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days.
  • Dihydroartemisinin-piperaquine for 3 days plus Mefloquine hydrochloride for 3 days.

Primary outcomes

  1. PCR corrected efficacy defined as adequate clinical and parasitological response (ACPR)

    Time frame: 42 days

Secondary outcomes

  1. Parasite clearance half-life

    Time frame: 42 days

    Parasite clearance half-life assessed by microscopy as primary parameter to de-termine parasite clearance

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

    Time frame: at 24 and 48 hours

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

    Time frame: 42 days

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

    Time frame: 42 days

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

    Time frame: 42 days

  6. Fever clearance time

    Time frame: 42 days

  7. Incidence of adverse events and serious adverse events

    Time frame: 42 days

  8. Incidence of adverse events concerning markers of hepatic toxicity

    Time frame: 42 days

    Total billirubin, ALT, AST and Alkaline Phosphatase will be measured

  9. Incidence of adverse events concerning markersof renal toxicity

    Time frame: 42 days

    Creatinine will be measured

  10. 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

  11. 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

  12. 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

  13. Prevalence of Kelch13 mutations of known functional significance

    Time frame: 42 days

  14. Prevalence/incidence of other genetic markers of antimalarial drug resistance

    Time frame: 42 days

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

    Time frame: 42 days

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

    Time frame: 42 days

  17. Transcriptomic patterns at t=0 and t=6h comparing sensitive and resistant parasites

    Time frame: 6hrs after start of treatment

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

    Time frame: 14 days

  19. Proportion of patients with gametocytemia before,after treatment with Primaquine

    Time frame: assessed at admission, up to day 14

  20. Levels of RNA transcription coding for male or female specific gametocytes

    Time frame: at admission up to day 14

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

    Time frame: 42 days

  22. • 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

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

    Time frame: Day 7

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Registry information

Official study 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

Acronym: TRACII

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
May 25, 2015
Registry last updated
May 9, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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