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

NCT ID: NCT03355664

Last Updated: 2022-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-19
• Study Completion Date: 2020-03-04

Brief Summary

This study is 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. The estimated total sample size is 600 patients from 2 sites in Cambodia and 2 sites in Vietnam. There are 2 treatment arms Arm 1: Artemether-lumefantrine for 3 days Arm 2: Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. According to the World Health Organization guideline, all patients except children under 10 kilograms will also be treated with a single dose of primaquine as a gametocytocidal treatment.

Funder :Bill & Melinda Gates Foundation (BMGF) Grant reference number: OPP1132628

Detailed Description

"The study of artemether-lumefantrine or artemether-lumefantrine combined with amodiaquine will be a two-arm randomized open label comparative study.

The main activity proposed is a series of detailed in vivo clinical, parasitological and pharmacological assessments in 600 subjects across 2 sites in Cambodian (400 subjects) and 2 sites in Vietnam (200 subjects). The subjects will be randomized between the ACT artemether-lumefantrine and the TACT artemether-lumefantrine+amodiaquine.

Parasite clearance rates will be assessed by repeated assessments of the parasite counts after the start of the antimalarial treatments. Efficacy, safety and tolerability of ACTs and TACTs will be assessed through weekly follow up visits where vital signs, symptom questionnaires, physical examinations, blood smears, biochemistry assays and full blood counts will be performed.

Ex vivo assessments of parasite susceptibility to artemisinins and partner drugs will be measured and compared to historical data, clinical phenotype and other sites in an effort to identify artemisinin and partner drug resistance.

This study will obtain data on the effect of antimalarials on the corrected QT intervals. In addition, the effects of antimalarials on factors such as post-treatment haematocrit and haemoglobin levels will be assessed. Extensive pharmacokinetic analysis will allow for an assessment of drug-drug interactions.

Plasma histidine-rich protein 2 (HRP2) levels (a marker of parasite biomass) that could potentially serve for the estimation of parasitaemia dynamics before and after treatment will be measured and subsequently modelled."

Conditions

Malaria, Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ACT

Artemether-lumefantrine for 3 days plus primaquine at hour 24

Group Type: ACTIVE_COMPARATOR

ACT

Intervention Type: DRUG

Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24

TACT

Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days plus primaquine at hour 24

Group Type: EXPERIMENTAL

TACT

Intervention Type: DRUG

Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24

Interventions

ACT

Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24

Intervention Type: DRUG

TACT

Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Siem Pang Health Center

Siem Pang, Stung Treng, Cambodia

Pailin Referral Hospital

Pailin, , Cambodia

Hospital for Tropical Diseases of Khanh Hoa,

Vạn Giã, Khanh Hoa, Vietnam

Phuoc Long Hospital

Phước Long, Phuoc, Vietnam

Countries

Cambodia; Vietnam

References

Peto TJ, Tripura R, Callery JJ, Lek D, Nghia HDT, Nguon C, Thuong NTH, van der Pluijm RW, Dung NTP, Sokha M, Van Luong V, Long LT, Sovann Y, Duanguppama J, Waithira N, Hoglund RM, Chotsiri P, Chau NH, Ruecker A, Amaratunga C, Dhorda M, Miotto O, Maude RJ, Rekol H, Chotivanich K, Tarning J, von Seidlein L, Imwong M, Mukaka M, Day NPJ, Hien TT, White NJ, Dondorp AM. Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial. Lancet Infect Dis. 2022 Jun;22(6):867-878. doi: 10.1016/S1473-3099(21)00692-7. Epub 2022 Mar 8.

Reference Type: BACKGROUND

PMID: 35276064 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MAL17008

Identifier Type: -

Identifier Source: org_study_id