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A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.

Pasaribu AP, Chokejindachai W, Sirivichayakul C, Tanomsing N, Chavez I, Tjitra E, Pasaribu S, Imwong M, White NJ, Dondorp AM - J. Infect. Dis. (2013)

Bottom Line: Which combination is most effective and safe remains to be established.Both treatments were safe, but DHP + PQ was better tolerated.NCT01288820.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established.

Methods: We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year.

Results: Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ.

Conclusions: In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated.

Clinical trials registration: NCT01288820.

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Related in: MedlinePlus

Kaplan–Meier analysis for recurrent infection during the 1-year follow-up period. Abbreviations: AAQ + PQ, artesunate-amodiaquine plus primaquine; DHP + PQ, dihydroartemisinin-piperaquine plus primaquine.
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JIT407F3: Kaplan–Meier analysis for recurrent infection during the 1-year follow-up period. Abbreviations: AAQ + PQ, artesunate-amodiaquine plus primaquine; DHP + PQ, dihydroartemisinin-piperaquine plus primaquine.

Mentions: Intention-to-treat survival analysis showed an adequate parasitological cure rate at 42 days of 91% (95% confidence interval [CI], 86%–95%) with AAQ + PQ and 94% (95% CI, 91%–98%) with DHP + PQ (Figure 2, log-rank P = .51). Per-protocol analysis of patients with complete 42-day follow-up showed cure rates of 100% (95% CI, 98%–100%; 138 of 138 patients) with AAQ + PQ and 99.3% (95% CI, 97%–99.9%; 150 of 151 patients) with DHP + PQ (P = .31). Parasite clearance was within 48 hours in both treatment arms, except for 1 patient with early treatment failure after DHP + PQ (who received rescue treatment) and another 2 patients after DHP + PQ who cleared parasites after >72 hours; neither showed recurrent infection during follow-up. No late treatment failures until day 42 were found in either treatment group. During 1-year follow-up, recurrent infections were observed in 15 of 130 (11.5%) patients after AAQ + PQ (of whom 2 had a second recurrent P. vivax infection) and 13 of 143 (9.1%) after DHP + PQ (Figure 3, log-rank P = .48). The earliest recurrence after treatment with AAQ + PQ was at day 54 compared to 83 days after DHP + PQ. After 1 year, the mean day of recurrence was day 165 (SD, 70) for patients treated with AAQ + PQ and day 203 (SD, 91) for those treated with DHP + PQ (P = .23). Among 28 patients with recurrent infections, 24 had monoinfection with P. vivax, 2 had monoinfection with P. falciparum, and 2 had mixed infection (P. falciparum/P. vivax). Cumulative risk of recurrence for the total group during the 1-year follow-up period was 17.5 per 100 person-years.Figure 2.


A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.

Pasaribu AP, Chokejindachai W, Sirivichayakul C, Tanomsing N, Chavez I, Tjitra E, Pasaribu S, Imwong M, White NJ, Dondorp AM - J. Infect. Dis. (2013)

Kaplan–Meier analysis for recurrent infection during the 1-year follow-up period. Abbreviations: AAQ + PQ, artesunate-amodiaquine plus primaquine; DHP + PQ, dihydroartemisinin-piperaquine plus primaquine.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814843&req=5

JIT407F3: Kaplan–Meier analysis for recurrent infection during the 1-year follow-up period. Abbreviations: AAQ + PQ, artesunate-amodiaquine plus primaquine; DHP + PQ, dihydroartemisinin-piperaquine plus primaquine.
Mentions: Intention-to-treat survival analysis showed an adequate parasitological cure rate at 42 days of 91% (95% confidence interval [CI], 86%–95%) with AAQ + PQ and 94% (95% CI, 91%–98%) with DHP + PQ (Figure 2, log-rank P = .51). Per-protocol analysis of patients with complete 42-day follow-up showed cure rates of 100% (95% CI, 98%–100%; 138 of 138 patients) with AAQ + PQ and 99.3% (95% CI, 97%–99.9%; 150 of 151 patients) with DHP + PQ (P = .31). Parasite clearance was within 48 hours in both treatment arms, except for 1 patient with early treatment failure after DHP + PQ (who received rescue treatment) and another 2 patients after DHP + PQ who cleared parasites after >72 hours; neither showed recurrent infection during follow-up. No late treatment failures until day 42 were found in either treatment group. During 1-year follow-up, recurrent infections were observed in 15 of 130 (11.5%) patients after AAQ + PQ (of whom 2 had a second recurrent P. vivax infection) and 13 of 143 (9.1%) after DHP + PQ (Figure 3, log-rank P = .48). The earliest recurrence after treatment with AAQ + PQ was at day 54 compared to 83 days after DHP + PQ. After 1 year, the mean day of recurrence was day 165 (SD, 70) for patients treated with AAQ + PQ and day 203 (SD, 91) for those treated with DHP + PQ (P = .23). Among 28 patients with recurrent infections, 24 had monoinfection with P. vivax, 2 had monoinfection with P. falciparum, and 2 had mixed infection (P. falciparum/P. vivax). Cumulative risk of recurrence for the total group during the 1-year follow-up period was 17.5 per 100 person-years.Figure 2.

Bottom Line: Which combination is most effective and safe remains to be established.Both treatments were safe, but DHP + PQ was better tolerated.NCT01288820.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT

Background: A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established.

Methods: We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year.

Results: Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ.

Conclusions: In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated.

Clinical trials registration: NCT01288820.

Show MeSH
Related in: MedlinePlus