Efficacy and Safety of Dihydroartemisinin/Piperaquine (Artekin®) for the Treatment of Uncomplicated Malaria in Peru
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Dihydroartemisin-piperaquine; Mefloquine + Artesunate
Intervention type(s): Drug; Drug
Intervention description(s): Dihydroartemisin-piperaquine (Artekin) manufactured by Hualijian Pharmaceutical Co. Ltd., Guangzhou, China. Each tablet contains 40mg of dihydroartemisinin and 320mg piperaquine; 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 intervention name(s): Artekin; MAS3
Intervention MeSH terms: Artesunate; Piperaquine; Mefloquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non complicated malaria; Microscopy; Adult; Children