Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria

December 2, 2016 updated by: GlaxoSmithKline

A Multi-centre, Randomised, Double-blind, Double Dummy Study Comparing the Efficacy and Safety of Chlorproguanil-dapsone-artesunate Versus Artemether-lumefantrine in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Children and Adolescents in Africa.

Chlorproguanil-dapsone has been approved for the treatment of uncomplicated Plasmodium falciparum malaria in a number of countries across sub-Sahara Africa, and by the UK's Medicines and Healthcare products Regulatory Agency.

CDA is a combination of chlorproguanil, dapsone and artesunate, being developed in a public-private partnership with the Medicines for Malaria Venture (MMV), World Health Organisation (WHO-TDR) and academic partners from the London School of Hygiene and Tropical Medicine, University of Liverpool and the Liverpool School of Tropical Medicine as a treatment for acute uncomplicated P. falciparum malaria.

The combination of chlorproguanil-dapsone-artesunate (CDA) is being developed to supersede chlorproguanil-dapsone for the same indication, but the addition of an artemisinin derivative, artesunate, should provide additional population benefits over chlorproguanil-dapsone alone. The artemisinins have been demonstrated to rapidly reduce parasite load and have activity against the sexual stages of the P.falciparum lifecycle. The addition of a second agent to the chlorproguanil-dapsone combination should also protect against the selection of resistant strains of P.falciparum.

Artemether-lumefantrine is the only available fixed-dose Artemisinin-based Combination Therapy actually available and is considered as the gold standard for the treatment of P. falciparum malaria. This study will therefore aim to demonstrate the non-inferiority of the combination of CDA to artemether-lumefantrine in terms of efficacy at 28-days. The key secondary objectives will compare the Parasite Clearance Times (PCT) and the Fever Clearance Times (FCT) between CDA and artemether-lumefantrine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1395

Phase

  • Phase 3

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

  • Burkina Faso
      • Bobo-Dioulasso, Burkina Faso
        • GSK Investigational Site
  • Ghana
      • Kintampo, Ghana
        • GSK Investigational Site
  • Kenya
      • Eldoret, Kenya
        • GSK Investigational Site
      • Kilifi, Kenya
        • GSK Investigational Site
  • Nigeria
      • Barkin Ladi, Nigeria
        • GSK Investigational Site
      • Calabar, Nigeria
        • GSK Investigational Site
      • Enugu, Nigeria
        • GSK Investigational Site
      • Ibadan, Nigeria
        • GSK Investigational Site
  • Tanzania
      • Ifakara, Tanzania
        • GSK Investigational Site

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

1 year to 14 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Acute, uncomplicated P.falciparum malaria, microscopically confirmed
  • Temperature at screening of 37.5oC or or more or confirmed history of fever within previous 24 hours
  • Weigh 7.5kg or over
  • Screening haemoglobin (Hb) of 7g/dl or over, or haematocrit of 25% or more(If Hb not available at screening)
  • Willingness to comply with the study visits and procedures, as outlined in the informed consent form
  • Written or oral witnessed consent has been obtained from parent or guardian
  • Assent is given by a child aged 12 years or over, in addition to the consent of their parent or guardian

Exclusion criteria:

  • Features of severe/complicated falciparum malaria
  • Hypersensitivity to active substances (chlorproguanil, dapsone, artesunate, artemether, lumefantrine)
  • Known allergy to biguanides, sulphones, sulphonamides, artemisinin derived products or aminoalcohol drugs
  • Known history of G6PD deficiency
  • Infants with a history of hyperbilirubinaemia during the neonatal period
  • Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the WHO (World Health Organization) list of essential drugs
  • Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae)
  • Any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease)
  • Malnutrition, defined as a child whose weight-for-height is below -3 standard deviations or less than 70% of the median of the NCHS/WHO normalised reference values
  • Treatment within the past three months with mefloquine or mefloquine-sulphadoxine-pyrimethamine; twenty-eight days with sulphadoxine/pyrimethamine, sulfalene/pyrimethamine, lumefantrine or artemether/lumefantrine, amodiaquine, atovaquone or atovoquone/proguanil, halofantrine; 14-days with chlorproguanil/dapsone, or 7-days with quinine (full course), proguanil, artemisinins, tetracycline doxycycline or clindamycin
  • Positive sulphadoxine/pyrimethamine urine screen for 'unknown' antimalarial drug use in prior 28-days
  • Use of an investigational drug within 30 days or 5 half-lives whichever is the longer
  • Previous participation in this study
  • Female subjects of child-bearing age, who have had a positive pregnancy test at screening, or do not give their consent to take a pregnancy test
  • Female subjects who will be breast-feeding an infant for the duration of the study

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Drug: artemether-lumefantrine
Other Names:
  • chlorproguanil-dapsone-artesunate
Drug: chlorproguanil-dapsone-artesunate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Parasitological cure rate, PCR corrected, at day 28 in the PP population The ITT population is a key supportive analysis.

Secondary Outcome Measures

Outcome Measure
Parasitological cure rate, PCR-corrected, at day 14 and 42 ACPR, and ACPR PCR corrected at day 14, 28 and 42 Summary of asexual parasite densities on days 0, 1, 2, 3, 7, 14, 28 and 42 by treatment group.

Collaborators and Investigators

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

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

June 1, 2006

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

August 1, 2007

Study Registration Dates

First Submitted

June 22, 2006

First Submitted That Met QC Criteria

June 22, 2006

First Posted (Estimate)

June 26, 2006

Study Record Updates

Last Update Posted (Estimate)

December 5, 2016

Last Update Submitted That Met QC Criteria

December 2, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDA 714703/005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Clinical Study Report
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Annotated Case Report Form
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Informed Consent Form
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Study Protocol
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Statistical Analysis Plan
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Individual Participant Data Set
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Dataset Specification
    Information identifier: CDA 714703/005
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

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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