Efficacy Study of Amodiaquine-Artesunate and Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria
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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 |
- 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.
- 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:
|
|
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:
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 |
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| Congo, The Democratic Republic of the | |
| General reference hospital of Chamfubu | |
| Pweto, Katanga, Congo, The Democratic Republic of the | |
| 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 Protozoan Infections Parasitic Diseases Amodiaquine Artemether Artesunate Artemisinins Lumefantrine Artemether-lumefantrine combination Amodiaquine, artesunate drug combination Antimalarials |
Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents Coccidiostats Schistosomicides Antiplatyhelmintic Agents Anthelmintics Amebicides |
ClinicalTrials.gov processed this record on May 19, 2013