Chlorproguanil-Dapsone-Artesunate (CDA) Versus Chlorproguanil-Dapsone (LAPDAP) For Uncomplicated Malaria

NCT ID: NCT00371735

Last Updated: 2016-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

900 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2007-05-31

Brief Summary

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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 HCl (CPG) and dapsone (DDS) as chlorproguanil-dapsone has already been shown to be efficacious against P.falciparum in adults and children in Sub-Sahara Africa. The addition of artesunate to LAPDAP has been demonstrated to increase the parasite kill rate as demonstrated in the phase II study, and reduce the chance of any parasites escaping treatment over the 3-day course. The addition of artesunate is also anticipated to have the population benefit of protection against the development of resistant strains of P.falciparum, although it will not be possible to demonstrate this in a clinical trial. One further population benefit of the artemisinin drugs are their ability to suppress the sexual forms of the parasite (gametocytes), which should reduce infectivity after antimalarial treatment and potentially lower transmission rates with widespread use, including the spread of any parasites resistant to the partner drug.

The aims of this phase III study are to compare the efficacy of a fixed ratio combination tablet of CDA to chlorproguanil-dapsone, and collect supporting safety data. This will be a multi-centre, double-blind, double-dummy, randomised trial, in children, adolescents and adults, with chlorproguanil-dapsone as a comparator.

Detailed Description

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Conditions

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Malaria, Falciparum

Keywords

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Malaria CDA LAPDAP Africa

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm 1

Group Type EXPERIMENTAL

chlorproguanil-dapsone-artesunate

Intervention Type DRUG

chlorproguanil-dapsone

Intervention Type DRUG

Interventions

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chlorproguanil-dapsone-artesunate

Intervention Type DRUG

chlorproguanil-dapsone

Intervention Type DRUG

Other Intervention Names

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chlorproguanil-dapsone-artesunate

Eligibility Criteria

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Inclusion Criteria

* Acute, uncomplicated P.falciparum malaria, microscopically confirmed infection.
* Temperature at screening of 37.5oC or over or confirmed history of fever within previous 24-hours.
* Weight 7.5kg or over , no upper weight limit.
* Screening haemoglobin (Hb) of 7g/dl, or more or haematocrit of 25% or over(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 obtained from subject, parent or guardian.
* Assent is given by a child aged 12 to \<18years, 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), or excipients of the investigational products.
* Known allergy to biguanides, sulphones, sulphonamides or artemisinin derived products.
* Known history of G6PD deficiency.
* Infants with a history of hyperbilirubinaemia during the neonatal period.
* Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae).
* Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the WHO (World Health Organization) list of essential drugs.
* 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 atovaquone/proguanil, halofantrine; 14-days with chlorproguanil/dapsone, or 7-days with quinine (full course), proguanil, artemisinin, 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 potential who have had a positive pregnancy test at enrolment, 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.
Minimum Eligible Age

12 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Ouagadougou, , Burkina Faso

Site Status

GSK Investigational Site

Kumasi, , Ghana

Site Status

GSK Investigational Site

Bamako, , Mali

Site Status

GSK Investigational Site

Ile-Ife, , Nigeria

Site Status

GSK Investigational Site

Jos, , Nigeria

Site Status

GSK Investigational Site

Lagos, , Nigeria

Site Status

GSK Investigational Site

Maiduguri, , Nigeria

Site Status

Countries

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Burkina Faso Ghana Mali Nigeria

References

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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.

Reference Type DERIVED
PMID: 22993389 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21849081 (View on PubMed)

Study Documents

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Document Type: Annotated Case Report Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Document Type: Dataset Specification

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.clinicalstudydatarequest.com

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Other Identifiers

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CDA 714703/006

Identifier Type: -

Identifier Source: org_study_id