Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00344006
First received: June 22, 2006
Last updated: May 15, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: chlorproguanil-dapsone-artesunate
Drug: artemether-lumefantrine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

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

Secondary Outcome Measures:
  • 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.

Estimated Enrollment: 1395
Study Start Date: June 2006
Intervention Details:
    Drug: chlorproguanil-dapsone-artesunate Drug: artemether-lumefantrine
    Other Names:
    • chlorproguanil-dapsone-artesunate
    • artemether-lumefantrine
  Eligibility

Ages Eligible for Study:   12 Months to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00344006

Locations
Burkina Faso
GSK Investigational Site
Bobo-Dioulasso, Burkina Faso
Ghana
GSK Investigational Site
Kintampo, Ghana
Kenya
GSK Investigational Site
Eldoret, Kenya
GSK Investigational Site
Kilifi, Kenya
Nigeria
GSK Investigational Site
Barkin Ladi, Nigeria
GSK Investigational Site
Calabar, Nigeria
GSK Investigational Site
Ibadan, Nigeria
Tanzania
GSK Investigational Site
Ifakara, Tanzania
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00344006     History of Changes
Other Study ID Numbers: CDA 714703/005
Study First Received: June 22, 2006
Last Updated: May 15, 2009
Health Authority: Nigeria: National Agency for Food and Drug Administration and Control (NAFDAC)
Tazania: Tanzania Food and Drug Authority (TFDA)
Kenya: Pharmacy and Poisons Board
Ghana: Food and Drugs Board (FDB)

Keywords provided by GlaxoSmithKline:
Malaria CDA COARTEM Africa pediatrics children

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Lumefantrine
Artemether
Artemisinins
Artesunate
Proguanil
Dapsone
Chlorproguanil
Artemether-lumefantrine combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Enzyme Inhibitors
Leprostatic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on October 19, 2014