Tolerability and Efficacy of CD+A Compared to AQ+SP for the Treatment of P.Falciparum Malaria in Rwandan Children

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461578
• Other study ID #: CDA/RWD/2006
• Status: Completed
• Phase: N/A
• First received: April 16, 2007
• Last updated: April 16, 2007
• Start date: April 2005
• Est. completion date: October 2006

Study information

• Verified date: April 2007
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical 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. Adverse events, clinical and parasitological outcomes were recorded.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 59 Months

Eligibility

Inclusion Criteria:

• 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%.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• Chlorproguanil-dapsone + artesunate

Locations

Country	Name	City	State
Rwanda	Programme Nationale Integre de Lutte contre le Paludisme	Kigali

Sponsors (2)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Institute of Tropical Medicine, Belgium

Country where clinical trial is conducted

Rwanda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28
Secondary	Parasite clearance
Secondary	Fever clearance
Secondary	Occurrence of adverse events