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

This study has been completed.
Sponsor:
Information provided by:
Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier:
NCT00373607
First received: September 7, 2006
Last updated: September 13, 2010
Last verified: September 2010
  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: Dihydroartemisin-piperaquine
Drug: Mefloquine + Artesunate
Phase 3

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Adequate Clinical and parasitological response [ Time Frame: Day 63 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recrudescence [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  • Reinfections [ Time Frame: day 63 ] [ Designated as safety issue: No ]
  • SAE [ Time Frame: Day 63 ] [ Designated as safety issue: Yes ]
  • AE [ Time Frame: Day 63 ] [ Designated as safety issue: Yes ]

Enrollment: 522
Study Start Date: July 2003
Study Completion Date: July 2005
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dihydroartemisin-piperaquine
Dihydroartemisin-piperaquine (Artekin, Hualijian Pharmaceutical Co. Ltd., Guangzhou, China). Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine
Drug: Dihydroartemisin-piperaquine
Dihydroartemisin-piperaquine (Artekin) manufactured by Hualijian Pharmaceutical Co. Ltd., Guangzhou, China. Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine
Other Name: Artekin
Active Comparator: Mefloquine + Artesunate (MAS3)
The MAS3 regimen is artesunate 4 mg/kg/day once daily for 3 days plus mefloquine 24 mg/kg given as a three day regimen of 8mg/kg/day
Drug: Mefloquine + Artesunate
Mefloquine + Artesunate (MAS3). The regimen is artesunate 4 mg/kg/day once daily for 3 days plus mefloquine 24 mg/kg given as a three day regimen of 8mg/kg/day
Other Name: MAS3

Detailed Description:

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.

  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 equal or higher than 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided by Institute of Tropical Medicine, Belgium

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: prof Umberto D'Aessandro, Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT00373607     History of Changes
Other Study ID Numbers: ARTEKINPERU
Study First Received: September 7, 2006
Last Updated: September 13, 2010
Health Authority: Peru: Ministry of Health

Keywords provided by Institute of Tropical Medicine, Belgium:
Non complicated malaria
Microscopy
Adult
Children

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Mefloquine
Artesunate
Artemisinins
Dihydroquinghaosu
Piperaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Amebicides

ClinicalTrials.gov processed this record on July 26, 2014