Efficacy Study of Amodiaquine-Artesunate and Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria

This study has been completed.
Sponsor:
Collaborator:
Medecins Sans Frontieres, Spain
Information provided by (Responsible Party):
Epicentre
ClinicalTrials.gov Identifier:
NCT01567423
First received: January 27, 2009
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention
Malaria, Falciparum
Drug: ASAQ Winthrop® Sanofi Aventis
Drug: Coartem®, Novartis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Amodiaquine-Artesunate and Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Pweto, Democratic Republic of Congo, 2008

Resource links provided by NLM:


Further study details as provided by Epicentre:

Primary Outcome Measures:
  • PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population [ Time Frame: 42 days ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    A survival analysis was performed and patients with incomplete follow-up who did not reach the primary outcome interest were included in the analysis as non-failures, but censored on the last day of follow-up. The risk of failure was calculated using the Kaplan-Meier product limit formula with data censored for patients who were not classified as failures and with interrupted follow-up. Patients wrongly included, who did not meet study inclusion criteria, were excluded from both analyses.

  • PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • PCR-adjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • PCR-unadjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment: 301
Study Start Date: April 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Artesunate and Amodiaquine (ASAQ)
children receiving fixed-dose combination of artesunate and amodiaquine
Drug: ASAQ Winthrop® Sanofi Aventis
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
Other Names:
  • COARSUCAM 25 mg/67,5 mg
  • COARSUCAM 50 mg/135 mg
  • COARSUCAM 100 mg/270 mg
Active Comparator: Arthemeter and Lumefantrine (AL)
children receiving fixed-dose combination of arthemeter and lumefantrine
Drug: Coartem®, Novartis

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)
Other Name: RIAMET

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Age between 6 and 59 months
  • Weight ≥ 5 Kg
  • P. falciparum infections (density threshold at inclusion between 2,000 and 200,000/µl)
  • Fever (≥ 37.5°C) or history of fever in the previous 24 hours

Exclusion criteria:

  • severe or complicated malaria
  • reported hypersensitivities of the studied drugs
  • serious concomitant febrile illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567423

Locations
Congo, The Democratic Republic of the
General reference hospital of Chamfubu
Pweto, Katanga, Congo, The Democratic Republic of the
Sponsors and Collaborators
Epicentre
Medecins Sans Frontieres, Spain
Investigators
Principal Investigator: Emmanuelle Espié, PhD Epicentre
  More Information

No publications provided by Epicentre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Epicentre
ClinicalTrials.gov Identifier: NCT01567423     History of Changes
Other Study ID Numbers: Epicentre-MSF-OCBA, ESP/CE/012/2008, CPP 08013
Study First Received: January 27, 2009
Last Updated: March 28, 2012
Health Authority: Congo, Democratic Republic of the : Comité National d'Ethique en Santé CNES, Comité d'éthique de l'Ecole de santé publique, Kinshasa

Keywords provided by Epicentre:
Malaria
Plasmodium falciparum
Children
Efficacy
Uncomplicated malaria

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Parasitic Diseases
Protozoan Infections
Amodiaquine
Amodiaquine, artesunate drug combination
Artemether
Artemether-lumefantrine combination
Artemisinins
Artesunate
Lumefantrine
Amebicides
Anthelmintics
Anti-Infective Agents
Antifungal Agents
Antimalarials
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Coccidiostats
Pharmacologic Actions
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014