NCT03355664

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
310

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Mar 2018

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 1, 2017

Completed
27 days until next milestone

First Posted

Study publicly available on registry

November 28, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

March 19, 2018

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 4, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 4, 2020

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

July 15, 2022

Completed
Last Updated

July 15, 2022

Status Verified

March 1, 2022

Enrollment Period

2 years

First QC Date

November 1, 2017

Results QC Date

October 14, 2021

Last Update Submit

March 17, 2022

Conditions

Malaria, Falciparum

Keywords

Malaria, FalciparumMalariaProtozoan InfectionsLumefantrineArtemetherAmodiaquinePiperaquineArtemether-lumefantrine combinationArtemisininsDihydroartemisininMefloquineArtemisininAntimalarialsAntiparasitic AgentsAnti-Infective AgentsACTTACTTriple ACT(s)ResistanceAntimalarial resistanceCardiotoxicitySafetyTolerabilityEfficacy

Outcome Measures

Primary Outcomes (1)

  • Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm

    Efficacy is defined as participants, following initial parasite and fever clearance, not having a recrudescence of the original plasmodium infection and fever, up to 42 days of follow up.

    42 days

Secondary Outcomes (27)

  • 42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region

    42 day

  • Parasite Clearance Half-life

    42 day

  • Fever Clearance Time

    42 day

  • Number of Severe Adverse Events by Study Arm

    42 days

  • Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity

    42 day

  • +22 more secondary outcomes

Study Arms (2)

ACT

ACTIVE COMPARATOR

Artemether-lumefantrine for 3 days plus primaquine at hour 24

Drug: ACT

TACT

EXPERIMENTAL

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

Drug: TACT

Interventions

ACTDRUG

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

ACT
TACTDRUG

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

TACT

Eligibility Criteria

Age2 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Siem Pang Health Center

Siem Pang, Stung Treng, 1803, Cambodia

Location

Pailin Referral Hospital

Pailin, 2401, Cambodia

Location

Hospital for Tropical Diseases of Khanh Hoa,

Vạn Giã, Khanh Hoa, Vietnam

Location

Phuoc Long Hospital

Phước Long, Phuoc, Vietnam

Location

Related Publications (1)

  • 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.

    PMID: 35276064BACKGROUND

MeSH Terms

Conditions

Malaria, FalciparumMalariaProtozoan InfectionsCardiotoxicity

Interventions

bis(tetraheptylammonium)tetraiodocyclopentane tellurate(IV)

Condition Hierarchy (Ancestors)

Parasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne DiseasesHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and Injuries

Results Point of Contact

Title
Thomas Peto
Organization
Mahidol Oxford Tropical Medicine Research Unit (MORU)
tom@tropmedres.ac
(+66) 802 187 460

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: open-label randomised trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 2017

First Posted

November 28, 2017

Study Start

March 19, 2018

Primary Completion

March 4, 2020

Study Completion

March 4, 2020

Last Updated

July 15, 2022

Results First Posted

July 15, 2022

Record last verified: 2022-03

Locations

CA(2)VN(2)