A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities
A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities
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DOI：
10.1093/jac/dkw333
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发表时间：
2016-12-01
影响因子：
5.2
通讯作者：
Gonzalez, Jesus
中科院分区：
文献类型：
--
作者：
Dryden, Matthew;Zhang, Yingyuan;Gonzalez, Jesus
目的：每 12 小时增加头孢洛林酯剂量超过 600 mg 可能会给患有严重炎症和/或病原体敏感性降低的复杂皮肤和软组织感染 (cSSTI) 的患者带来额外的益处。一项 III 期多中心、随机试验评估了在此情况下每 8 小时 600 mg 头孢洛林酯的安全性和有效性。 方法：患有 cSSTI 和全身炎症或合并症的成年患者以 2:1 的比例随机分配至静脉注射头孢洛林酯（每 8 小时 600 mg）或万古霉素（每 12 小时 15 mg/kg）加氨曲南（每 8 小时 1 g）治疗。 5-14 天。在改良 ITT (MITT) 和临床可评估 (CE) 人群中，通过治愈测试 (TOC) 访视（最终剂量后 8-15 天）评估临床治愈情况。非劣效性定义为治疗差异周围的 95% CI 下限大于 -10%。主要研究完成后，开始了以 MRSA 为重点的扩展期。 ClinicalTrials.gov 注册号 NCT01499277 和 NCT02202135。 结果：TOC 的临床治愈率表明，在 MITT 和 CE 人群中，每 8 小时 600 mg 头孢洛林酯与万古霉素加氨曲南相比具有非劣效性：396/506 (78.3%) 与 202/255 (79.2%) 患者（差异 21.0%、95% CI 26.9、5.4）和 342/395 (86.6%) 与 180/211 (85.3%) 例患者（差异 1.3%、95% CI24.3、7.5）分别。在扩展期，3/4（75%）接受头孢洛林酯治疗的患者在 TOC 时治愈。各组之间不良事件的发生频率相似。 结论：每 8 小时一次 600 mg 头孢洛林酯对于有全身炎症和/或合并症证据的 cSSTI 患者有效。没有发现新的安全信号。
Objectives: Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting.Methods: Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2: 1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days. Clinical cure was assessed at the test of cure (TOC) visit (8-15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than -10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135.Results: Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference 21.0%, 95% CI 26.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI24.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups.Conclusions: Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified.