A Trial to Compare the Efficacy, Safety and Tolerability of Combinations of 3 Anti-malarial Drugs Against Combina-tions of 2 Anti-malarial Drugs.

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 (ASMQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (ASMQ+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.

Conditions

• Plasmodium Falciparum Malaria (Uncomplicated)

Interventions

DRUG

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. AQ: 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.

DRUG

Artemether-lumefantrine + placebo (AL+PBO)

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.

DRUG

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. 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.

DRUG

Artesunate-mefloquine+placebo (AS-MQ+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. PBO: Placebo tablets for piperaquine are identical in size, shape and colour to the piperaquine tablets.

Sponsors & Collaborators

• Mahidol Oxford Tropical Medicine Research Unit

  collaborator OTHER

• University of Oxford

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-09-01

Primary Completion

2024-03-15

Completion

2024-03-15

Countries

• Burkina Faso
• Democratic Republic of the Congo
• Guinea
• Nigeria
• Niger
• Rwanda
• Tanzania
• The Gambia

Study Locations