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

NCT01755559 | Completed Phase 4

• 1 other identifier: Epicentre/Nig/2012/Palu3ACT
• Study Type: interventional
• Target: 663
• Locations: 1 country
• Sites: 1

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).

Conditions

Malaria

Keywords

malaria; artemisinin; artemisinin-based combination therapies; Plasmodium falciparum; efficacy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Early treatment failure

  1 to 3 days after tratment start

• Late clinical failure

  from day 4 to day 42 after treatment start

• Late Parasitological Failure

  from day 7 to day 42 after treatment start

Study Arms (3)

Artesunate-amodiaquine

OTHER

Efficacy estimates at 95%

Drug: Artesunate-amodiaquine

Dihydroartemisinin-piperaquine

OTHER

Efficacy estimates at 95%

Drug: Dihydroartemisinin-piperaquine

Artemether-lumefantrine

OTHER

Efficacy estimates at 95%

Drug: Artemether-lumefantrine

Interventions

Artesunate-amodiaquine DRUG

antimalarial ACT

Also known as: AS-AQ Winthrop® Sanofi Aventis

Artesunate-amodiaquine

Dihydroartemisinin-piperaquine DRUG

antimalarial ACT

Also known as: Euratesim, Sigma-Tau

Dihydroartemisinin-piperaquine

Artemether-lumefantrine DRUG

antimalarial ACT

Also known as: Coartem, Novartis

Artemether-lumefantrine

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Epicentre: lead
• Centre de Recherche Médicale et Sanitaire (Cermes), Niamey: collaborator

Study Sites (1)

Andoumé Health Centre

Maradi, Maradi Region, Niger

Location

Related Publications (1)

• 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.

  PMID: 29370844 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

amodiaquine, artesunate drug combination; Artemether, Lumefantrine Drug Combination; lactitol

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Francesco Grandesso, MSc

  Epicentre

  PRINCIPAL INVESTIGATOR

• Lynda Woi Messe, MD

  Epicentre

  STUDY CHAIR

• Ibrahim M Laminou, PhD

  Cermes

  STUDY CHAIR

• Jean-François Etard, PhD

  Epicentre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 24, 2012
• Study Start: June 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 30, 2015

Record last verified: 2015-11

Locations

NI (1)