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
Summary
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-lifeParasite 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 hemoglobin/hematocrit 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)
Eligibility
Minimum age: 6 Months.
Maximum age: 65 Years.
Gender(s): Both.
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 (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
months.
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
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