MalariaNCT00461578
Tolerability and Efficacy of CD+A Compared to AQ+SP for the Treatment of P.Falciparum Malaria in Rwandan Children
A study testing Chlorproguanil-dapsone + artesunate in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Rwanda.
Trial summary
In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Read more about this study
- Who is it for?
- Ages 12 to 59 months
- Conditions the study is for
- Malaria
- What is being tested?
- Chlorproguanil-dapsone + artesunate
- How many people
- 800 participants
- Where
- 1 siteRwanda
- Study dates
- Apr 2005to Oct 2006
- Phase
- Interventional
- 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 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 12-59 months;
- Weight ≥5 kg;
- Monoinfection with P. falciparum;
- Parasite density between 2,000-200,000/µL;
- Fever (axillary body temperature =>37.5C) or history of fever in the preceding 24 hours;
- Packed Cell Volume (PCV) >21%.
Who cannot join
- Severe malaria;
- Mixed malaria infection;
- Any other concomitant illness or underlying disease;
- Known allergy to the study drugs being used in this trial;
- Clear history of adequate antimalarial treatment in the previous 72 hours.
Trial locations and contacts
1 site in 1 country.
Rwanda1 site
Programme Nationale Integre de Lutte contre le Paludisme
Kigali, BP 2514
About this study
Official title: Open Study on the Tolerability and Efficacy of the Combination Chlorproguanil-Dapsone+Artesunate Compared to Amodiaquine+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria in Rwandan Children
In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded.
Read the detailed description
Between 2001 and 2006, as an interim strategy, Rwanda chose amodiaquine+ sulfadoxine-pyrimethamine (AQ+SP) as the first line anti-malaria treatment. Although the clinical response to this combination was relatively good in 2001, since then its efficacy has steadily declined: in 2002 the proportion of successful treatment (recorded at 28 days and PCR-unadjusted) was 83 % (Rwagacondo et al., 2003) and in 2003 it was 74% (Karema et al., 2006). Different artemisinin-based combination treatments (ACTs) such as amodiaquine+artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPPQ) and artemether-lumefantrine (ALN) have been tested in the past few years as possible alternatives to AQ+SP (Fanello et al., 2006; Karema et al., 2006).
Chlorproguanil-dapsone (also known asLapDap) is an antifolate combination similar to sulfadoxine/pyrimethamine (SP) but for two important features: (1) it is rapidly eliminated and therefore exerts less selective pressure for resistance-conferring parasite mutations than does SP (Winstanley et al., 1997; Nzila et al., 2000b) and (2) it is active against the SP-resistant forms of the parasite that are found in Africa (Mutabingwa et al., 2001a,b; Kublin et al., 2002). Moreover, a pediatric course of treatment of LapDap is estimated to cost $0.15 (Mutabingwa et al., 2001b), making it orders of magnitude less expensive than any marketed antimalarial drug other than chloroquine and SP.
In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded.
Based on the results of all trials carried out by the NMCP, The Rwandan Ministry of Health has now changed the first line to artemether-lumefantrine (ALN), Coartem®. The drug arrived in the country in October 2006.
- Conditions
- Malaria
- Being tested
- Chlorproguanil-dapsone + artesunate
- Keywords
- P.falciparum, malaria, lapdap+artesunate, safety, efficay
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chlorproguanil-dapsone + artesunateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28
Secondary outcomes (3)
Parasite clearance
Fever clearance
Occurrence of adverse events
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2007 (estimated)
- Study startApr 2005
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 800 participants
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Tropical Medicine, Belgium
- Investigators
- Umberto d'Alessandro, MD, Study director, ITM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00461578
- Sponsor's protocol ID
- CDA/RWD/2006
- Status last verified
- Apr 2007
- First submitted
- 16 Apr 2007
- Last updated
- 18 Apr 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Fanello CI, Karema C, Avellino P, Bancone G, Uwimana A, Lee SJ, d'Alessandro U, Modiano D. High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PLoS One. 2008;3(12):e4031. doi: 10.1371/journal.pone.0004031. Epub 2008 Dec 29.
PubMed 19112496Fanello CI, Karema C, Ngamije D, Uwimana A, Ndahindwa V, Van Overmeir C, Van Doren W, Curtis J, D'Alessandro U. A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone + artesunate for the treatment of uncomplicated Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2008 May;102(5):412-20. doi: 10.1016/j.trstmh.2008.01.013. Epub 2008 Mar 6.
PubMed 18328518
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Study on the Tolerability and Efficacy of the Combination Chlorproguanil-Dapsone+Artesunate Compared to Amodiaquine+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria in Rwandan Children
- ClinicalTrials.gov ID
- NCT00461578
- Acronym / sponsor ID
- CDA/RWD/2006
- Conditions
- Malaria
- Keywords
- P.falciparum, malaria, lapdap+artesunate, safety, efficay
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 800 participants
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Institute of Tropical Medicine, Belgium
- Study start
- Apr 2005
- Study completion
- Oct 2006 (actual)
- First posted
- 18 Apr 2007 (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.
In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded.
Detailed description
Between 2001 and 2006, as an interim strategy, Rwanda chose amodiaquine+ sulfadoxine-pyrimethamine (AQ+SP) as the first line anti-malaria treatment. Although the clinical response to this combination was relatively good in 2001, since then its efficacy has steadily declined: in 2002 the proportion of successful treatment (recorded at 28 days and PCR-unadjusted) was 83 % (Rwagacondo et al., 2003) and in 2003 it was 74% (Karema et al., 2006). Different artemisinin-based combination treatments (ACTs) such as amodiaquine+artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPPQ) and artemether-lumefantrine (ALN) have been tested in the past few years as possible alternatives to AQ+SP (Fanello et al., 2006; Karema et al., 2006).
Chlorproguanil-dapsone (also known asLapDap) is an antifolate combination similar to sulfadoxine/pyrimethamine (SP) but for two important features: (1) it is rapidly eliminated and therefore exerts less selective pressure for resistance-conferring parasite mutations than does SP (Winstanley et al., 1997; Nzila et al., 2000b) and (2) it is active against the SP-resistant forms of the parasite that are found in Africa (Mutabingwa et al., 2001a,b; Kublin et al., 2002). Moreover, a pediatric course of treatment of LapDap is estimated to cost $0.15 (Mutabingwa et al., 2001b), making it orders of magnitude less expensive than any marketed antimalarial drug other than chloroquine and SP.
In 2005-2006, a clinical trial was carried out to test safety, tolerability and efficacy of the combination chlorproguanil-dapsone+artesunate (CD+A): 800 children aged 12-59 months with uncomplicated P. falciparum malaria randomly allocated to AQ+SP or CD+A were followed up until day 28 after treatment. Adverse events, clinical and parasitological outcomes were recorded.
Based on the results of all trials carried out by the NMCP, The Rwandan Ministry of Health has now changed the first line to artemether-lumefantrine (ALN), Coartem®. The drug arrived in the country in October 2006.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 12 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age 12-59 months;
- Weight ≥5 kg;
- Monoinfection with P. falciparum;
- Parasite density between 2,000-200,000/µL;
- Fever (axillary body temperature =>37.5C) or history of fever in the preceding 24 hours;
Key exclusion criteria (5 listed)
- Severe malaria;
- Mixed malaria infection;
- Any other concomitant illness or underlying disease;
- Known allergy to the study drugs being used in this trial;
- Clear history of adequate antimalarial treatment in the previous 72 hours.
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 | – |
Primary outcome
Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28
3 secondary outcomes
Parasite clearance
Fever clearance
Occurrence of adverse events
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 18 Apr 2007.
- Derived from this study: PubMed 19112496Fanello CI, Karema C, Avellino P, Bancone G, Uwimana A, Lee SJ, d'Alessandro U, Modiano D. High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PLoS One. 2008;3(12):e4031. doi: 10.1371/journal.pone.0004031. Epub 2008 Dec 29.
- Derived from this study: PubMed 18328518Fanello CI, Karema C, Ngamije D, Uwimana A, Ndahindwa V, Van Overmeir C, Van Doren W, Curtis J, D'Alessandro U. A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone + artesunate for the treatment of uncomplicated Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2008 May;102(5):412-20. doi: 10.1016/j.trstmh.2008.01.013. Epub 2008 Mar 6.
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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.
Umberto d'Alessandro, MD study director
ITM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chlorproguanil-dapsone + artesunate in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Rwanda.
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 6 inclusion and 5 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 18 Apr 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Rwanda. 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.
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?
Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28. 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 NCT00461578, which also lists 2 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 18 Apr 2007.