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Efficacy and Safety of Dihydroartemisinin/Piperaquine (Artekin®) for the Treatment of Uncomplicated Malaria in Peru

This study has been completed.

Sponsored by: Institute of Tropical Medicine, Belgium
Information provided by: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT00373607
  Purpose

In Peru, Mefloquine plus Artesunate (MAS3), is the current first line treatment for P. falciparum malaria in the Amazonian Region, and has proved its efficacy against multi-resistant P. falciparum parasites, but several side effects have been reported. Dihydroartemisinin-piperaquine (DHA-PPQ) is a new co-formulated and well tolerated ACT, increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria. We tested the efficacy, safety and tolerability of DHA-PPQ in patients with uncomplicated P. falciparum malaria. A RCT to evaluate DHA-PPQ was carried out, between 2003 and 2005. Patients with uncomplicated P. falciparum malaria were randomly allocated to receive either DHA-PPQ or MAS3 with a 63-day follow-up period. Five hundred twenty two patients were included in the analysis, 262 were allocated to receive DHA-PPQ, and 260 to receive MAS3. The two groups were comparable at baseline in demographic and clinical characteristics. The mean time for parasite clearance into the DHA-PPQ group was 32.0 hours and 35.5 hours in the MAS3 group. Twenty-four hours after the first dose, the proportions of patients whose cleared parasitaemia were 67.2% in the DHA-PPQ group, and 58.1% in the MAS3 group (RR 1.25, [95% CI 1.03−1.52], p = 0.017). All patients were able to clear parasites within 72 hours after the first dose. The mean time for fever clearance was 28.0 and 29.5 hours in DHA-PPQ and MAS3 group respectively. (P= 0.69). Twenty-four hours after the first dose, 85.5% and 83.1% of patients cleared fever in the DHA-PPQ and MAS3 group respectively (p>0.05). The Adequate Clinical and Parasitological Response (ACPR), PCR adjusted, were 97.7% and 99,2% for the DHA-PPQ and MAS3 group respectively, (RR 0.99, 95% CI [0.86−1.13], P = 0.88). No Early Treatments Failures were reported in any group. In the DHA-PPQ group, according to the PCR adjusted results, 6 subjects had Late treatment Failures. In the MAS3 group, two Late Treatment Failures was reported. The frequency of adverse events was significantly lower in patients treated with DHA-PPQ than in those treated with MAS3.

DHA-PPQ proved to be a highly effective antimalarial drug for the treatment of P. falciparum malaria and suitable for use in the Peruvian Amazon region. It also has the advantage of being better tolerated. In terms of cost, DHA-PPQ is cheaper and more affordable than MAS3 and should be considered for the National Antimalarial Drug Policy in Perú.


Condition Intervention Phase
Malaria
Drug: Dihydroartemisinin/piperaquine VS. Mefloquine + Artesunate
Phase III

MedlinePlus related topics:   Malaria   

ChemIDplus related topics:   Artesunate    Dihydroquinghaosu    Piperaquine    Mefloquine    Mefloquine hydrochloride   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:   Phase 3a: Efficacy, Safety, and Tolerability of Dihydroartemisinin/Piperaquine (Artekin®) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Peruvian Amazon Region

Further study details as provided by Institute of Tropical Medicine, Belgium:

Primary Outcome Measures:
  • Adequate Clinical and parasitological response at day 63

Secondary Outcome Measures:
  • Recrudescence till day 63
  • Reinfections till day 63
  • SAE till day 63
  • AE till day 63

Estimated Enrollment:   522
Study Start Date:   July 2003
Estimated Study Completion Date:   July 2005

  Eligibility
Ages Eligible for Study:   5 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  • Age: 5 - 60 years old
  • Fever (axillary temperature  37,5 °C) or history of fever in the previous 24 hours
  • Monoinfection with P. falciparum, with parasitic density between 1,000 and 200,000 par/µl
  • Informed consent provided by patient or parent or legal tutor

    • Exclusion criteria:

  • Mixed malaria infection
  • Pregnancy or breastfeeding to child ≤ 6 months of age
  • One or more danger signs or any sign of severe or complicated malaria
  • A concomitant severe disease
  • History of treatment with mefloquine in the last 60 days or chloroquine, primaquine or quinine within the 14 days before the present episode
  • History of neuropsychiatric disease
  • History of hypersensitivity reactions to artemisinins or mefloquine
  • History of splenectomy
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373607

Sponsors and Collaborators
Institute of Tropical Medicine, Belgium

Investigators
Study Director:     Umberto D'Alessandro, MD,MSc, PHD     Institute of Tropical Medicine, Antwerp    
  More Information


Publications indexed to this study:

Study ID Numbers:   ARTEKINPERU
First Received:   September 7, 2006
Last Updated:   September 7, 2006
ClinicalTrials.gov Identifier:   NCT00373607
Health Authority:   Belgium: Central Committee of bioethics;   PERU: institute of tropical medecine Alexander von Humboltd

Keywords provided by Institute of Tropical Medicine, Belgium:
Non complicated Malaria adults children Trial  
Non pregnant adults with symptomatic malaria confirmed by microscopy  
Children from 5 to 18 years with symptomatic malaria confirmed by microscopy  

Study placed in the following topic categories:
Artesunate
Piperaquine
Protozoan Infections
Artemisinins
Artemisinine
Parasitic Diseases
Malaria
Mefloquine
Dihydroquinghaosu
Malaria, Falciparum

Additional relevant MeSH terms:
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Coccidiosis
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2008




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