Clinical trial NCT01755559: Efficacy of Three ACTs for the Treatment of Falciparum Malaria in Maradi Niger
Official title: Efficacy of Artesunate-amodiaquine, Dihydroartemisinin-piperaquine and Artemether-lumefantrine Combination Therapies for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Aged 6 to 59 Months in Maradi, Niger 2012-13
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: malaria
artemisinin
artemisinin-based combination therapies
Plasmodium falciparum
efficacy
Lead sponsor: Epicentre
Sponsor class: OTHER
Collaborators: name: Centre de Recherche Médicale et Sanitaire (Cermes), Niamey
First posted: 2012-12-24
Enrollment: 663
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Adequate clinical and parasitological response
timeFrame: 42 days after treatement start
Secondary outcomes:
measure: Early treatment failure
timeFrame: 1 to 3 days after tratment start
measure: Late clinical failure
timeFrame: from day 4 to day 42 after treatment start
measure: Late Parasitological Failure
timeFrame: from day 7 to day 42 after treatment start
Other outcomes:
Locations:
city: Maradi
country: Niger
facility: Andoumé Health Centre
Study officials:
affiliation: Epicentre
name: Francesco Grandesso, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Epicentre
name: Lynda Woi Messe, MD
role: STUDY_CHAIR
affiliation: Cermes
name: Ibrahim M Laminou, PhD
role: STUDY_CHAIR
affiliation: Epicentre
name: Jean-François Etard, PhD
role: STUDY_CHAIR
References:
citation: Grandesso F, Guindo O, Woi Messe L, Makarimi R, Traore A, Dama S, Laminou IM, Rigal J, de Smet M, Ouwe Missi Oukem-Boyer O, Doumbo OK, Djimde A, Etard JF. Efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger. Malar J. 2018 Jan 25;17(1):52. doi: 10.1186/s12936-018-2200-1.