Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria

NCT00344006 | Completed Phase 3

• 1 other identifier: CDA 714703/005
• Study Type: interventional
• Target: 1,395
• Locations: 5 countries
• Sites: 9

Brief Summary

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.

Conditions

Malaria, Falciparum

Keywords

Malaria CDA COARTEM Africa pediatrics children

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (1)

• 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.

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: chlorproguanil-dapsone-artesunate; Drug: artemether-lumefantrine

Interventions

chlorproguanil-dapsone-artesunate DRUG

Arm 1

artemether-lumefantrine DRUG

Also known as: chlorproguanil-dapsone-artesunate

Arm 1

Eligibility Criteria

• Age: 12 Months - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Bobo-Dioulasso, Burkina Faso

Location

GSK Investigational Site

Kintampo, Ghana

Location

GSK Investigational Site

Eldoret, Kenya

Location

GSK Investigational Site

Kilifi, Kenya

Location

GSK Investigational Site

Barkin Ladi, Nigeria

Location

GSK Investigational Site

Calabar, Nigeria

Location

GSK Investigational Site

Enugu, Nigeria

Location

GSK Investigational Site

Ibadan, Nigeria

Location

GSK Investigational Site

Ifakara, Tanzania

Location

Related Publications (3)

• Pamba A, Richardson ND, Carter N, Duparc S, Premji Z, Tiono AB, Luzzatto L. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood. 2012 Nov 15;120(20):4123-33. doi: 10.1182/blood-2012-03-416032. Epub 2012 Sep 19.

  PMID: 22993389 DERIVED

• Carter N, Pamba A, Duparc S, Waitumbi JN. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011 Aug 17;10:241. doi: 10.1186/1475-2875-10-241.

  PMID: 21849081 DERIVED

• Premji Z, Umeh RE, Owusu-Agyei S, Esamai F, Ezedinachi EU, Oguche S, Borrmann S, Sowunmi A, Duparc S, Kirby PL, Pamba A, Kellam L, Guiguemde R, Greenwood B, Ward SA, Winstanley PA. Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria. PLoS One. 2009 Aug 19;4(8):e6682. doi: 10.1371/journal.pone.0006682.

  PMID: 19690618 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 26, 2006
• Study Start: June 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: August 1, 2007
• Last Updated: December 5, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will share

Locations

GH (1); TA (1); KE (2); BU (1); NG (4)