NCT03939104

Brief Summary

A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine + amodiaquine (AL+AQ) and artesunate- mefloquine+piperaquine (AS-MQ+PPQ) with the ACTs artemether-lumefantrine + placebo (AL+PBO) and artesunate- mefloquine + placebo (AS-MQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
103

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2021

Geographic Reach
2 countries

3 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

April 29, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 6, 2019

Completed
2.2 years until next milestone

Study Start

First participant enrolled

June 30, 2021

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 6, 2023

Completed
22 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 28, 2023

Completed
Last Updated

March 20, 2024

Status Verified

May 1, 2023

Enrollment Period

1.5 years

First QC Date

April 29, 2019

Last Update Submit

March 18, 2024

Conditions

Keywords

ArtemetherLumefantrineAmodiaquinePiperaquineArtesunateMefloquine

Outcome Measures

Primary Outcomes (1)

  • Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR).

    42 days

Secondary Outcomes (17)

  • Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR)

    63-day

  • Efficacy defined as adequate clinical and parasitological response (PCR)

    63-day

  • Efficacy defined as adequate clinical and parasitological response (ACPR)

    42-day

  • Parasite clearance half-life

    7 days

  • proportion of subjects with microscopically detectable P. falciparum parasitaemia

    3 days

  • +12 more secondary outcomes

Other Outcomes (15)

  • Comparison of efficacy, defined as PCR corrected adequate clinical and parasitological response (ACPR) at day 42 versus day 63

    63 days

  • Comparison of efficacy, defined as adequate clinical and parasitological response (ACPR) at day 42 versus day 63

    63 days

  • Proportions of recurrent infections with parasites carrying mutations of known functional significance

    63 days

  • +12 more other outcomes

Study Arms (4)

Artemether-lumefantrine+amodiaquine (AL+AQ)

ACTIVE COMPARATOR

Triple ACTs

Drug: Artemether-lumefantrine+amodiaquine

Artesunate-mefloquine+piperaquine (AS-MQ+PPQ)

ACTIVE COMPARATOR

Triple ACTs

Drug: Artesunate-mefloquine+piperaquine

artemether-lumefantrine+placebo (AL+PBO)

ACTIVE COMPARATOR

ACTs

Drug: Artemether-lumefantrine+placebo

Artesunate-mefloquine+placebo (AS-MQ+PBO)

ACTIVE COMPARATOR

ACTs.

Drug: Artesunate-mefloquine+placebo

Interventions

AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. AQ: Amodiaquine is available as dispersible tablets of 40 mg. The weight-based treatment schedule aims for a dosage of approximately 10mg (4.5-15mg)/kg/day amodiaquine for three days.

Artemether-lumefantrine+amodiaquine (AL+AQ)

AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. PBO: Placebo tablets for amodiaquine are identical in size, shape and color to the amodiaquine tablets.

artemether-lumefantrine+placebo (AL+PBO)

AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PPQ: Piperaquine will be administered according to an optimised dosing schedule using tablets of 160 or 500 mg of piperaquine tetraphosphate. The weight-based treatment aims for a dosage of approximately * 24 mg/kg/day in patients \<25 kg (range 16.0 - 32.0 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 20 - 32 mg/kg per day. * 18 mg/kg/day in patients ≥25 kg (range 15.0 - 29.4 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 16 - 27 mg/kg per day.

Artesunate-mefloquine+piperaquine (AS-MQ+PPQ)

AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PBO: Placebo tablets for piperaquine are identical in size, shape and colour to the piperaquine tablets.

Artesunate-mefloquine+placebo (AS-MQ+PBO)

Eligibility Criteria

Age6 Months+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female, \>/= 6 months
  • Ability to take oral medication
  • Acute uncomplicated P. falciparum monoinfection
  • Asexual P. falciparum parasitaemia: 96 to 200,000/µL, determined on a peripheral blood film
  • Fever defined as \>/= 37.5°C tympanic temperature or a history of fever within the last 24 hours
  • Written informed consent by the subject or parent/guardian in case of children lower than the age of consent and assent if required (per local regulations)
  • Willingness and ability of the subjects or parents/guardians to comply with the study protocol for the duration of the study

You may not qualify if:

  • Signs of severe malaria (adapted from WHO criteria)
  • Patients not fulfilling criteria for severe malaria but with another indication for parenteral antimalarial treatment at the discretion of the treating physician
  • Haematocrit \< 20% at screening
  • Subjects who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquine within the previous 30 days
  • Acute illness other than malaria requiring systemic treatment
  • Severe acute malnutrition
  • Known HIV infection
  • Known tuberculosis infection
  • For females: pregnant, trying to get pregnant or are lactating
  • History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy
  • Previous splenectomy
  • Enrolment in DeTACT in the previous 3 months
  • Participation in another interventional study in the previous 3 months
  • Criteria for severe malaria
  • Impaired consciousness (Glasgow Coma Scale, Blantyre Coma Scale)
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Ramu Upazilla Health Complex

Cox’s Bāzār, Chittagong, Bangladesh

Location

Kravanh Referral Hospital

Phnum Kravanh, Pursat, 150501, Cambodia

Location

Siem Pang Health Center

Siem Pang, Stung Treng, 1803, Cambodia

Location

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine+amodiaquine (AL+AQ) and artesunate- mefloquine+piperaquine (AS-MQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (AS-MQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 29, 2019

First Posted

May 6, 2019

Study Start

June 30, 2021

Primary Completion

January 6, 2023

Study Completion

January 28, 2023

Last Updated

March 20, 2024

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will share

With participant's consent, participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with data repositories such as the WorldWide Antimalarial Resistance Network (WWARN, terms of submission here: http://www.wwarn.org/tools-resources/terms-submission) or other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records, through interviews, or from mapping data.

Time Frame
After completion of trial activities and reporting
Access Criteria
MORU Data Sharing Policy: https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing WWARN terms of Data Access: http://www.wwarn.org/tools-resources/terms-reshouces/terms-data-access
More information

Locations