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

NCT ID: NCT00373607

Last Updated: 2010-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 522 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2005-07-31

Brief Summary

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.

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dihydroartemisin-piperaquine

Dihydroartemisin-piperaquine (Artekin, Hualijian Pharmaceutical Co. Ltd., Guangzhou, China). Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine

Group Type: EXPERIMENTAL

Dihydroartemisin-piperaquine

Intervention Type: DRUG

Dihydroartemisin-piperaquine (Artekin) manufactured by Hualijian Pharmaceutical Co. Ltd., Guangzhou, China. Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine

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

Group Type: ACTIVE_COMPARATOR

Mefloquine + Artesunate

Intervention Type: DRUG

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

Interventions

Dihydroartemisin-piperaquine

Dihydroartemisin-piperaquine (Artekin) manufactured by Hualijian Pharmaceutical Co. Ltd., Guangzhou, China. Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Artekin; MAS3

Eligibility 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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Institute of Tropical Medicine, Belgium

Principal Investigators

Umberto D'Alessandro, MD,MSc, PHD

Role: STUDY_DIRECTOR

Institute of Tropical Medicine Antwerp

References

Grande T, Bernasconi A, Erhart A, Gamboa D, Casapia M, Delgado C, Torres K, Fanello C, Llanos-Cuentas A, D'Alessandro U. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS One. 2007 Oct 31;2(10):e1101. doi: 10.1371/journal.pone.0001101.

Reference Type: DERIVED

PMID: 17971864 (View on PubMed)

Other Identifiers

ARTEKINPERU

Identifier Type: -

Identifier Source: org_study_id