Malaria, FalciparumPhase 3NCT00344006
Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria
A Phase 3 study testing chlorproguanil-dapsone-artesunate and artemether-lumefantrine in people with Malaria, Falciparum, run by GlaxoSmithKline at 9 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 14 years
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- chlorproguanil-dapsone-artesunate and artemether-lumefantrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,395 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Jun 2006to Aug 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Nigeria4 sites
GSK Investigational Site
Barkin Ladi
GSK Investigational Site
Calabar
GSK Investigational Site
Enugu
GSK Investigational Site
Ibadan
About this study
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.
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.
Read more
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
- Being tested
- chlorproguanil-dapsone-artesunate, artemether-lumefantrine
- Keywords
- Malaria CDA COARTEM Africa pediatrics children
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chlorproguanil-dapsone-artesunateDrug
artemether-lumefantrineDrug
Also called chlorproguanil-dapsone-artesunate
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: chlorproguanil-dapsone-artesunate; Drug: artemether-lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2006 (estimated)
- Study startJun 2006
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malaria, FalciparumStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,395 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00344006
- Sponsor's protocol ID
- CDA 714703/005
- Status last verified
- Dec 2016
- First submitted
- 22 Jun 2006
- Last updated
- 5 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 22993389Carter 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.
PubMed 21849081Premji 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.
PubMed 19690618
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00344006
- Acronym / sponsor ID
- CDA 714703/005
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria CDA COARTEM Africa pediatrics children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,395 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 26 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: chlorproguanil-dapsone-artesunate, Drug: artemether-lumefantrine |
Who may qualify
- Ages
- 12 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| chlorproguanil-dapsone-artesunate | Drug | Arm 1 |
| artemether-lumefantrineAlso: chlorproguanil-dapsone-artesunate | Drug | Arm 1 |
Primary outcome
Parasitological cure rate, PCR corrected, at day 28 in the PP population The ITT population is a key supportive analysis.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Derived from this study: PubMed 22993389Pamba 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.
- Derived from this study: PubMed 21849081Carter 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.
- Derived from this study: PubMed 19690618Premji 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing chlorproguanil-dapsone-artesunate and artemether-lumefantrine in people with Malaria, Falciparum, run by GlaxoSmithKline at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Nigeria, Kenya, Burkina Faso, Ghana, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parasitological cure rate, PCR corrected, at day 28 in the PP population The ITT population is a key supportive analysis.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00344006, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2016.