Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials.
Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials.
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DOI：
10.1186/1475-2875-12-70
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发表时间：
2013-02-21
期刊：
影响因子：
3
通讯作者：
Fleckenstein L
中科院分区：
文献类型：
--
作者：
Duparc S;Borghini-Fuhrer I;Craft CJ;Arbe-Barnes S;Miller RM;Shin CS;Fleckenstein L
咯萘啶-青蒿琥酯（PA）适用于治疗急性无并发症的恶性疟原虫和间日疟原虫疟疾。整合了在非洲和亚洲进行的6项随机临床试验的个体患者安全性结局数据，这些试验在显微镜下证实为恶性疟原虫（5项研究）或间日疟原虫（1项研究）疟疾患者中进行。在三项III期临床试验中评价了对恶性疟原虫的疗效。安全性人群包括2，815例随机分配至PA组的患者，1，254例随机分配至对照药物组：甲氟喹+青蒿琥酯（MQ + AS）、蒿甲醚-苯芴醇（AL）或氯喹。所有治疗通常耐受良好。57.2%（1，611/2，815）的PA患者和51.5%（646/1，254）的对照药物患者发生了不良事件，最常见（PA;对照药物）：头痛（10.6%; 9.9%）、咳嗽（5.9%; 5.6%）和贫血（4.5%; 2.9%）。所有治疗中严重厌恶事件均不常见（0-0.7%）。PA组观察到丙氨酸转氨酶和天冬氨酸转氨酶一过性升高，但未导致任何临床后遗症。对于恶性疟原虫疟疾，PA治疗后第28天PCR校正的充分临床和寄生虫学应答在意向治疗人群中为93.6%（[1，921/2，052] 95% CI 92.6，94.7），在符合方案人群中为98.5%（[1，852/1，880] 95% CI 98.0，99.1）。PA、MQ + AS和AL的中位寄生虫清除时间分别为24.1 h、31.9 h和24.0 h。PA、MQ + AS和AL的中位发热清除时间分别为15.5 h、15.8 h和14.0 h。除转氨酶大多数轻度一过性升高外，咯萘啶-青蒿琥酯耐受性良好，无安全性问题。有效性高，符合用作一线治疗的要求。应考虑将咯萘啶-青蒿琥酯纳入疟疾治疗方案。Clinicaltrials.gov：NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931
Pyronaridine-artesunate (PA) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Individual patient data on safety outcomes were integrated from six randomized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum (five studies) or P. vivax (one study) malaria. Efficacy against P. falciparum was evaluated across three Phase III clinical trials. The safety population included 2,815 patients randomized to PA, 1,254 to comparators: mefloquine + artesunate (MQ + AS), artemether-lumefantrine (AL), or chloroquine. All treatments were generally well tolerated. Adverse events occurred in 57.2% (1,611/2,815) of patients with PA versus 51.5% (646/1,254) for comparators, most commonly (PA; comparators): headache (10.6%; 9.9%), cough (5.9%; 5.6%) and anaemia (4.5%; 2.9%). Serious averse events were uncommon for all treatments (0–0.7%). Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae. For P. falciparum malaria, day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6% ([1,921/2,052] 95% CI 92.6, 94.7) in the intent-to-treat population and 98.5% ([1,852/1,880] 95% CI 98.0, 99.1) in the per-protocol population. Median parasite clearance time was 24.1 h with PA, 31.9 h with MQ + AS, and 24.0 h with AL. Median fever clearance time was 15.5 h with PA, 15.8 h with MQ + AS, and 14.0 h with AL. By day 42, P. falciparum gametocytes had declined to near zero for all treatments. Pyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases. Efficacy was high and met the requirements for use as first-line therapy. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. Clinicaltrials.gov: NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931
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影响因子：
3
作者：
Mueller I;Widmer S;Michel D;Maraga S;McNamara DT;Kiniboro B;Sie A;Smith TA;Zimmerman PA
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Zimmerman PA
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3
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Hay SI
影响因子：
9.6
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通讯作者：
Hay, Simon I.
影响因子：
3
作者：
Agomo, Philip U.;Meremikwu, Martin M.;Aina, Olugbenga O.
通讯作者：
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