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

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01755559
• Other study ID #: Epicentre/Nig/2012/Palu3ACT
• Status: Completed
• Phase: Phase 4
• First received: December 19, 2012
• Last updated: November 26, 2015
• Start date: June 2013
• Est. completion date: November 2014

Study information

• Verified date: November 2015
• Source: Epicentre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Niger: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 663
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 59 Months

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• Artesunate-amodiaquine
antimalarial ACT
• Dihydroartemisinin-piperaquine
antimalarial ACT
• Artemether-lumefantrine
antimalarial ACT

Locations

Country	Name	City	State
Niger	Andoumé Health Centre	Maradi

Sponsors (2)

Lead Sponsor	Collaborator
Epicentre	Centre de Recherche Médicale et Sanitaire (Cermes), Niamey

Country where clinical trial is conducted

Niger, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adequate clinical and parasitological response	Absence of parasitaemia on day 42, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure.	42 days after treatement start	No
Secondary	Early treatment failure	General danger signs or signs of severe malaria on days 1, 2, or 3, in the presence of parasitaemia , or; Parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature, or; Parasitaemia on day 3 with axillary temperature = 37.5°C, or; Parasitaemia on day 3 = 25% count on day 0 irrespective of axillary temperature.	1 to 3 days after tratment start	No
Secondary	Late clinical failure	General danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 42 in patients who did not previously meet any of the criteria of early treatment failure; or; Presence of parasitaemia on any day between day 4 and day 42 with axillary temperature = 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure.	from day 4 to day 42 after treatment start	No
Secondary	Late Parasitological Failure	- Presence of parasitaemia on any day between day 7 and day 42 with axillary temperature < 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.	from day 7 to day 42 after treatment start	No