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In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated P. Falciparum Malaria

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ClinicalTrials.gov Identifier: NCT02637128
Recruitment Status : Completed
First Posted : December 22, 2015
Last Update Posted : December 22, 2015
Sponsor:
Collaborator:
University of Malawi College of Medicine
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Brief Summary:
This study was designed to determine the efficacy of both artemether-lumefantrine and artesunate-amodiaquine (but not to compare the efficacies of the two drugs) for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi.

Condition or disease Intervention/treatment Phase
MALARIA, FALCIPARUM Drug: artemether-lumefantrine (AL) Drug: artesunate-amodiaquine (ASAQ) Phase 4

Detailed Description:

Background: Malaria is a cause of substantial morbidity and mortality in Malawi. Prompt and effective treatment of uncomplicated malaria remains a key strategy to reduce the public health burden of malaria. Due to the rising resistance to and declining efficacy of sulfadoxine-pyrimethamine, the first-line treatment for uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007 and again in 2013. The revised treatment guidelines recommend artemether-lumefantrine as the first-line treatment for uncomplicated malaria and artesunate-amodiaquine as a second-line treatment for uncomplicated malaria. Data from Malawi suggests that these drugs remain efficacious. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious. A more recent assessment of artemether-lumefantrine in vivo efficacy conducted in six sites in Malawi in 2009 also suggests that the standard formulation artemether-lumefantrine remains highly efficacious. In addition, both the dispersible formulation of artemether-lumefantrine (Coartem-D™) and artesunate-amodiaquine were extremely well tolerated and safe in studies conducted in Malawi as well as in other Sub-Saharan African countries. Given the potential for development of parasite resistance, it is imperative to continue to monitor the efficacy of these drugs as long as they remain the recommended treatment regimens.

Objective: Determine the efficacy of artemether-lumefantrine and co-formulated artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi

Methods: A randomized drug efficacy trial will be conducted in Malawi. The trial will include 453 febrile children 6-59 months old with confirmed uncomplicated P. falciparum infection, seeking care at Machinga, Nkhotakota, and Karonga District Hospitals; 151 patients will be enrolled at each site (113 for artemether-lumefantrine and 38 for co-formulated artesunate-amodiaquine). Patients will be randomized to receive treatment with either the dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 452 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated Plasmodium Falciparum Malaria in Malawi, 2014
Study Start Date : March 2014
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: artemether-lumefantrine (AL)

20mg artemether/120 mg lumefantrine per tablet, Coartem-D™; Novartis, Basel, Switzerland administered following manufacturer's prescribed weight-based dosing, twice daily for 3 days.

5-14 kg: 1 tablet; 15-24: 2 tablets; 25-34 kg: 3 tablets; >34 kg: 4 tablets per dose

Drug: artemether-lumefantrine (AL)
Dispersible formulation of artemether-lumefantrine (Coartem-D™; 20mg artemether/120mg lumefantrine per tablet, Novartis, Switzerland) administered twice a day for 3 days according to manufacturer recommended dosing for weight
Other Name: Coartem

Experimental: artesunate-amodiaquine (ASAQ)
25mg artesunate/67.5 mg amodiaquine or 50 mg artesunate/135mg amodiaquine per tablet, Coarsucam™; Sanofi-Aventis, Paris, France administered following manufacturer's prescribed weight-based dosing, once daily for 3 days 4.5-8.9 kg: 1 25mg/67.5 mg tablet; 9-17.9 kg: 1 50mg/135 mg tablet; 18-35.9 kg 2 50mg/135 tablets; >36 kg: 4 50mg/135mg tablets per dose
Drug: artesunate-amodiaquine (ASAQ)
Co-formulated artesunate-amodiaquine (25mg artesunate/67.5mg amodiaquine and 50mg artesunate/135mg amodiaquine tablets) administered once a day for 3 days, according to manufacturer recommended dosing for weight
Other Name: Coarsucam




Primary Outcome Measures :
  1. Adequate clinical and parasitological response (ACPR) [ Time Frame: 28 days ]
    Absence of parasitaemia on day 28, assessed by microscopy, 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



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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 to 59 months
  • mono-infection with P. falciparum detected by microscopy
  • parasitaemia of 1,000-200,000/µl asexual forms
  • presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h
  • ability to swallow oral medication
  • ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule
  • informed consent from the parent or guardian of the child

Exclusion Criteria:

  • presence of general danger signs in children aged 6-59 months or signs of severe falciparum malaria according to the definitions of World Health Organization
  • mixed or mono-infection with another Plasmodium species detected by microscopy
  • presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score)
  • presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS)
  • regular medication that may interfere with antimalarial pharmacokinetics
  • history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatments

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): NCT02637128


Locations
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Malawi
Malaria Alert Center, University of Malawi College of Medicine, Blantyre, Malawi
Blantyre, Malawi
Sponsors and Collaborators
Centers for Disease Control and Prevention
University of Malawi College of Medicine
Investigators
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Principal Investigator: Don P Mathanga, MBBS, PhD 1. Malaria Alert Centre (MAC), University of Malawi College of Medicine, Blantyre, Malawi

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Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT02637128     History of Changes
Other Study ID Numbers: Malawi TES 2014
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: December 22, 2015
Last Verified: December 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Centers for Disease Control and Prevention:
MALARIA, FALCIPARUM
MALAWI
ARTEMETHER-LUMEFANTRINE
ARTESUNATE-AMODIAQUINE

Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Lumefantrine
Artemether
Amodiaquine
Artemether, Lumefantrine Drug Combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics