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

This study has been completed.
Sponsor:
Collaborator:
Institute of Tropical Medicine, Belgium
Information provided by:
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT00461578
First received: April 16, 2007
Last updated: NA
Last verified: April 2007
History: No changes posted
  Purpose

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.


Condition Intervention
Malaria
Drug: Chlorproguanil-dapsone + artesunate

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

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • Incidence of microscopically and genotypically confirmed recrudescent infections in the different treatment groups by day 28

Secondary Outcome Measures:
  • Parasite clearance
  • Fever clearance
  • Occurrence of adverse events

Estimated Enrollment: 800
Study Start Date: April 2005
Study Completion Date: October 2006
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.

  Eligibility

Ages Eligible for Study:   12 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00461578

Locations
Rwanda
Programme Nationale Integre de Lutte contre le Paludisme
Kigali, Rwanda, BP 2514
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Institute of Tropical Medicine, Belgium
Investigators
Study Director: Umberto d'Alessandro, MD ITM
  More Information

No publications provided by London School of Hygiene and Tropical Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00461578     History of Changes
Other Study ID Numbers: CDA/RWD/2006
Study First Received: April 16, 2007
Last Updated: April 16, 2007
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by London School of Hygiene and Tropical Medicine:
P.falciparum
malaria
lapdap+artesunate
safety
efficay

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Dapsone
Artesunate
Chlorproguanil
Proguanil
Sulfadoxine-pyrimethamine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Anti-Bacterial Agents
Amebicides
Antimetabolites

ClinicalTrials.gov processed this record on July 29, 2014