Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03355664
• Date of registration: 01/11/2017
• Prospective Registration: Yes
• Primary sponsor: University of Oxford
• Public title: Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam TACT-CV
• Scientific title: A Multi-centre, Open-label Randomised Trial to Assess the Efficacy, Safety and Tolerability of the Triple ACT Artemether-lumefantrine+Amodiaquine (AL+AQ) Compared to the ACT Artemether-lumefantrine (AL) in Uncomplicated Falciparum Malaria in Cambodia and Vietnam
• Date of first enrolment: March 19, 2018
• Target sample size: 312
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03355664
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Cambodia, Vietnam

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female, aged from 2 years 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: 16 to 200,000/microlitre, determined on a thin or
thick blood film

- 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 < 8 g/dL at screening

- 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

- History of allergy or known contraindication to artemisinins, lumefantrine or
amodiaquine

- Previous splenectomy

- corrected QT interval > 450 milliseconds at moment of presentation

- Documented or claimed history of cardiac conduction problems

- Previous participation in the current study or another study in the previous 3 months



Age minimum: 2 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Malaria, Falciparum

Intervention(s)

Drug: TACT

Drug: ACT

Primary Outcome(s)

polymerase chain reaction corrected efficacy defined as adequate clinical and parasitological response (ACPR) by study arm [Time Frame: 42 days]

Secondary Outcome(s)

Prevalence of Kelch13 mutations of known significance [Time Frame: 42 day]

Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations [Time Frame: 48 hours]

Correlation between quantitative polymerase chain reaction based versus microscopy based assessments of parasite clearance dynamics [Time Frame: 14 days]

42-day polymerase chain reaction corrected efficacy according to site/geographic region [Time Frame: 42 day]

Correlation between single nucleotide polymorphisms and whole genome sequencing [Time Frame: 42 day]

Levels of RNA transcription coding for male or female specific gametocytes [Time Frame: 14 days]

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

Correlation between the host genotype and the pharmacokinetics and pharmacodynamics of antimalarials [Time Frame: 42 day]

Fever clearance time [Time Frame: 42 day]

Parasite count to fall 99% [Time Frame: 42 days]

Parasite count to fall 50% [Time Frame: 42 days]

Pharmacokinetic profiles and interactions (Cmax) of artemisinin-derivatives and partner drugs [Time Frame: 42 days]

Incidence of adverse events concerning markers of hepatic or renal toxicity [Time Frame: 42 day]

Proportion of patients that reports completing a full course of observed TACT or ACT [Time Frame: 42 day]

Incidence of prolongation of the corrected QT interval [Time Frame: 28 day]

Parasite reduction rates [Time Frame: 24 and 48 hours]

Correlation between histidine-rich protein 2 (HRP2) based versus microscopy based assessments of parasite clearance dynamics [Time Frame: 42 days]

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

Parasite count to fall 90% [Time Frame: 42 days]

Pharmacokinetic profiles and interactions (AUC) of artemisinin-derivatives and partner drugs [Time Frame: 42 days]

Prolongation of the corrected QT interval [Time Frame: Hour 4, Hour 24, Hour 28, Hour 48, Hour 52, Hour 60, Hour 64, Day 7 and Day 28 and between these time points]

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

In vitro sensitivity of P. falciparum to artemisinins and partner drugs [Time Frame: At admission & subjects with recurrent parasitaemia, up to 42 days]

Proportion of patients with gametocytaemia before, during and after treatment with TACT or ACT [Time Frame: At admission and up to day 14]

A comparison of transcriptomic patterns between sensitive and resistant parasites [Time Frame: baseline and t = 6 hours]

Change in haematocrit [Time Frame: Day 1 to 7, 14, 21, 28, 35, 42]

Incidence of adverse events and serious adverse events by study arm [Time Frame: 42 day]

Secondary ID(s)

MAL17008

Source(s) of Monetary Support

Please refer to primary and secondary sponsors