NCT01567423

Brief Summary

In the Democratic Republic of Congo (DRC), malaria is an important cause of morbidity and mortality. It is estimated that malaria is responsible for 30% of admissions to hospital averaged throughout the country and for 25-30% mortality in children under five. In 2005, DRC adopted artesunate and amodiaquine (ASAQ) as first-line anti-malarial treatment. As WHO recommended that the efficacy of antimalarial drugs was monitored regularly to avoid an upsurge of mortality and morbidity due to continued use of ineffective drugs, a randomized, non-inferiority open-label trial was conducted in Katanga, in order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL), Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolledand randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. Between April 2008 and March 2009, 301 childrenwere included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131) in the ASAQ group and 15.2% (19/125) in the AL group). After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8) in the ASAQ group and 99.1% (95%CI, 94.9-99.9) in the AL group (difference -0.7%, one sided 95%CI -3.1). Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
301

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2008

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2008

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

January 27, 2009

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
3 years until next milestone

First Posted

Study publicly available on registry

March 30, 2012

Completed
Last Updated

March 30, 2012

Status Verified

March 1, 2012

Enrollment Period

1 year

First QC Date

January 27, 2009

Last Update Submit

March 28, 2012

Conditions

Malaria, Falciparum

Keywords

MalariaPlasmodium falciparumChildrenEfficacyUncomplicated malaria

Outcome Measures

Primary Outcomes (1)

  • PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population

    Outcomes were classified according to 2009 WHO guidelines as adequate clinical and parasitological response, early treatment failure, late clinical failure, late parasitological failure or follow-up interrupted. The per protocol population comprised only the patients who were followed throughout the protocol, defined follow-up period and in whom a clear treatment outcome can be determined. The risk of failure for each treatment group was calculated as the proportion of patients classified as failure divided by the number of patients in the evaluable population.

    42 days

Secondary Outcomes (5)

  • PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population

    42 days

  • PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis

    42 days

  • PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis

    42 days

  • PCR-adjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population

    28 days

  • PCR-unadjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population

    28 days

Study Arms (2)

Artesunate and Amodiaquine (ASAQ)

EXPERIMENTAL

children receiving fixed-dose combination of artesunate and amodiaquine

Drug: ASAQ Winthrop® Sanofi Aventis

Arthemeter and Lumefantrine (AL)

ACTIVE COMPARATOR

children receiving fixed-dose combination of arthemeter and lumefantrine

Drug: Coartem®, Novartis

Interventions

ASAQ Winthrop® Sanofi AventisDRUG

Artesunate 25mg / amodiaquine 67.5mg: 1 tab/day for 3 days in children 5 to 8.9 kg Artesunate 50mg / amodiaquine 135mg: 1 tab/day for 3 days in children 9 to 17.9 kg

Also known as: COARSUCAM 25 mg/67,5 mg, COARSUCAM 50 mg/135 mg, COARSUCAM 100 mg/270 mg
Artesunate and Amodiaquine (ASAQ)
Coartem®, NovartisDRUG

artemether 20 mg / lumefantrine 120 mg co-formulated tablets given as six twice-daily doses over three days: 1. tab/dose for children 5 to 14.9 kg (total 6 tabs) 2. tabs/dose for children 15 to 24.9 kg (total 12 tabs)

Also known as: RIAMET
Arthemeter and Lumefantrine (AL)

Eligibility Criteria

Age6 Months - 59 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age between 6 and 59 months
  • Weight ≥ 5 Kg
  • Fever (≥ 37.5°C) or history of fever in the previous 24 hours

You may not qualify if:

  • severe or complicated malaria
  • reported hypersensitivities of the studied drugs
  • serious concomitant febrile illness

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

General reference hospital of Chamfubu

Pweto, Katanga, Democratic Republic of the Congo

Location

Related Publications (1)

  • Espie E, Lima A, Atua B, Dhorda M, Flevaud L, Sompwe EM, Palma Urrutia PP, Guerin PJ. Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial. Malar J. 2012 May 25;11:174. doi: 10.1186/1475-2875-11-174.

    PMID: 22631564DERIVED

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

Artemether, Lumefantrine Drug Combinationlactitol

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Emmanuelle Espié, PhD

    Epicentre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 27, 2009

First Posted

March 30, 2012

Study Start

April 1, 2008

Primary Completion

April 1, 2009

Study Completion

April 1, 2009

Last Updated

March 30, 2012

Record last verified: 2012-03

Locations

DE(1)