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

December 18, 2015 updated by: Centers for Disease Control and Prevention

In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated Plasmodium Falciparum Malaria in Malawi, 2014

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

452

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malawi
      • Blantyre, Malawi
        • Malaria Alert Center, University of Malawi College of Medicine, Blantyre, Malawi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 4 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Coarsucam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

Kamuzu University of Health Sciences

Investigators

  • Principal Investigator: Don P Mathanga, MBBS, PhD, 1. Malaria Alert Centre (MAC), University of Malawi College of Medicine, Blantyre, Malawi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

December 17, 2015

First Submitted That Met QC Criteria

December 18, 2015

First Posted (Estimate)

December 22, 2015

Study Record Updates

Last Update Posted (Estimate)

December 22, 2015

Last Update Submitted That Met QC Criteria

December 18, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Malawi TES 2014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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