Efficacy of Three ACTs for the Treatment of Falciparum Malaria in Maradi Niger

Epicentre

Status and phase: Completed; Phase 4

Conditions: Malaria

Treatments: Drug: Artemether-lumefantrine; Drug: Dihydroartemisinin-piperaquine; Drug: Artesunate-amodiaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT01755559

Epicentre/Nig/2012/Palu3ACT

Details and patient eligibility

About

Study treatments:

• Artemether-lumefantrine
• Artesunate-amodiaquine
• Dihydroartemisinin-piperaquine

Location:

Maradi, Niger

Principal Objective:

To measure the clinical and parasitological efficacy of the three artemisinin combination therapies over a period of 42 days from the start of treatment and with polymerase chain reaction assay (PCR) adjustment.

Secondary objectives:

• To determine the blood concentration of the non-artemisinin component of the treatment (lumefantrine, desethylamodiaquine or piperaquine) at day 7
• To assess the incidence of adverse events during the follow-up period;
• To measure speed of parasite clearance

Methods:

In vivo non comparative study as for WHO standardised protocol. The study also measure the concentration of the non-artemisinin component.

Target population:

Children under 5 years of age consulting the integrated health centres of Andoumé and Dix-sept portes in Maradi.

Sample size:

221 patients per study treatment; 663 patients in total.

Treatment allocation:

Random.

Outcomes:

• Early treatment failure,
• Late clinical failure,
• Late parasitological failure,
• Adequate clinical and parasitological response.

Analysis:

• Cumulative success or failure rate (Kaplan-Meier analysis).
• Proportions of early treatment failures, late clinical failures, late parasitological failures, and adequate clinical and parasitological response (called also Per-protocol analysis).

Enrollment: 663 patients

Sex: All

Ages: 6 to 59 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age between 6 and 59 months
• Weight ≥ 5 kg
• Mono-infection with P. falciparum detected by microscopy
• Parasitic density between 2,000 and 200,000 asexual forms /µL of blood
• Axillary temperature ≥ 37.5°C or history of fever during the previous 24 hours
• Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule (home is within one hour of walk from the outpatient department, no near-term travel plans, etc.)
• Consent of a parent or guardian who is at least 18 years of age.

Exclusion criteria

• Presence of general danger signs as defined by the WHO,
• Presence of signs of severe malaria according to the definitions of WHO,
• Severe anemia (haemoglobin <5 g/dL),
• Known history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia,
• Family history of sudden death or of congenital prolongation of corrected QT interval,
• Use of antiarrhythmics or neuroleptics,
• Known history of hypersensitivity to any of the study medications,
• Severe malnutrition (defined as a weight-height ratio of < -3 z-score according to the 2006 WHO reference (20) and / or a mid-upper arm circumference lower than 115 mm and / or the presence of symmetrical oedema of the feet),
• Presence of a febrile condition due to a disease other than malaria (i.e. measles, acute lower respiratory tract infection, otitis media, tonsillitis, abscess, severe diarrhoea with dehydration, etc.)
• History of a full treatment course with one of the three study drugs in the past 28 days. The prior incomplete intake of one of the three study drugs or prior intake of antimalarial drugs not being tested in the study does not exclude a patient from participating in this study. However, information on these previous treatments will be carefully recorded.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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663 participants in 3 patient groups

Artesunate-amodiaquine

Other group

Description:

Efficacy estimates at 95%

Treatment:

Drug: Artesunate-amodiaquine

Dihydroartemisinin-piperaquine

Other group

Description:

Efficacy estimates at 95%

Treatment:

Drug: Dihydroartemisinin-piperaquine

Artemether-lumefantrine

Other group

Description:

Efficacy estimates at 95%

Treatment:

Drug: Artemether-lumefantrine