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

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ClinicalTrials.gov Identifier: NCT01567423
Recruitment Status : Completed
First Posted : March 30, 2012
Last Update Posted : March 30, 2012
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment
Malaria, Falciparum Drug: ASAQ Winthrop® Sanofi Aventis Drug: Coartem®, Novartis

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Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 301 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 2008
Primary Completion Date : April 2009
Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. 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 ]

    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 :
  1. 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 ]
  2. 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 ]
    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.

  3. 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 ]
  4. 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 ]
  5. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 59 Months   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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 ( Other Identifier: Ethics Review Board of Doctors without Borders )
CPP 08013 ( Other Identifier: Comité de protection des personnes Ile de France XI )
First Posted: March 30, 2012    Key Record Dates
Last Update Posted: March 30, 2012
Last Verified: March 2012

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

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