The efficacy and tolerability of artemisinin-piperaquine (Artequick®) versus artesunate-amodiaquine (Coarsucam™) for the treatment of uncomplicated Plasmodium falciparum malaria in south-central Vietnam

Abstract

BackgroundIn Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria. However, limited efficacy and tolerability data are available on alternative forms of ACT in Vietnam in case there is a reduction in the susceptibility of dihydroartemisinin-piperaquine. A study was conducted to compare the efficacy and tolerability of two fixed-dose formulations of ACT, artemisinin–piperaquine (Artequick®, ARPQ) and artesunate-amodiaquine (Coarsucam™, ASAQ) for the treatment of P. falciparum malaria in south-central Vietnam.MethodsA randomized, open-label trial was conducted comparing the efficacy of a two-day regimen of ARPQ (~2.8 mg/kg artemisinin plus ~17.1 mg/kg of piperaquine per day) and a three-day regimen of ASAQ (~4.7 mg/kg of artesunate plus ~12.6 mg/kg of amodiaquine per day) for the treatment of children and adults with uncomplicated falciparum malaria. Primary efficacy endpoint was day 42, PCR-corrected, parasitological cure rate. Secondary endpoints were parasite and fever clearance times and tolerability.ResultsOf 128 patients enrolled, 63 were administered ARPQ and 65 ASAQ. Of the patients who completed the 42 days follow-up period or had a recurrence of malaria, 55 were on ARPQ (30 children, 25 adults) and 59 were on ASAQ (31 children, 28 adults). Recrudescent parasitaemia was PCR-confirmed for one patient in each treatment group, with cure rates at day 42 of 98% (95% CI: 88–100) for both forms of ACT. The median parasite clearance time was significantly slower in the ARPQ group compared with the ASAQ group (48 h vs. 36 h, P<0.001) and fever clearance times were shorter in the ASAQ group (12 h vs. 24 h, P = 0.07). The two forms of ACT were well tolerated with no serious adverse events.ConclusionBoth forms of ACT were highly efficacious in the treatment of uncomplicated P. falciparum malaria. Although the two-day course of ARPQ was equally as effective as the three-day course of ASAQ, parasite and fever clearance times were shorter with ASAQ. Further studies are warranted in different regions of Vietnam to determine the nationwide efficacy of ASAQ.Trial registrationAustralian New Zealand Clinical Trials Registry Number, ACTRN12609000816257

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

“…For these reasons, amodiaquine may show some useful efficacy in SEA. This is also consistent with the acceptable clinical efficacy of artesunate–amodiaquine in some [59, 60], but not all [61], parts of SEA within the last decade. Furthermore, the inverse correlation between susceptibility to 4-aminoquinolines and mefloquine [62, 63] offers the potential to combine two partners with opposing resistance mechanisms within a novel ‘triple’ ACT, artemether–lumefantrine plus amodiaquine [64]; this is currently under investigation in the follow-up study to TRAC (ClinicalTrials.gov NCT02453308).…”

Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis

“…A total of 11 different clinical studies were shared with WWARN, containing 8,776 plasma piperaquine concentrations from 728 individuals that could be included in the pooled analysis (Fig 1) [22,24,25,27,29,30,39–43]. Demographic data are presented in Table 1.…”

“…Study reports generated from the formatted datasets were sent back to investigators for clarification and/or validation. Pharmacokinetic data from ten previously published clinical studies and one unpublished (at the time) clinical study were contributed and used for modelling [22,24,25,27,29,30,39–43]. Demographic data from each study are summarised in Table 1.…”

Monitoring the efficacy and safety of three artemisinin based-combinations therapies in Senegal: results from two years surveillance

“…Many studies have reported good efficacy of DHAPQ combination for malaria treatment [23-25]. The three antimalarial drugs remained highly effective at days 35 and 42.…”