eStudySite Clinical Research, San Diego, California, USA.
Physician Alliance Research Center, Anaheim, California, USA.
Clin Infect Dis. 2021 Oct 5;73(7):e1507-e1517. doi: 10.1093/cid/ciaa974.
The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens.
TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48-72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >-10%. Safety was assessed through adverse event and laboratory data collection.
In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: -1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles.
TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit.
NCT03137173.
新型广谱抗生素的开发具有治疗革兰阳性和革兰阴性细菌感染的功效，有可能为急性细菌性皮肤和皮肤结构感染（ABSSSIs）的治疗提供更多选择。头孢托罗匹酯是一种具有广泛体外活性的新型第四代头孢菌素，对革兰阳性菌（包括耐甲氧西林金黄色葡萄球菌）和革兰阴性病原体均有作用。
TARGET 是一项随机、双盲、阳性对照、平行分组、多中心、III 期非劣效性研究，比较头孢托罗匹酯与万古霉素加氨曲南的疗效。美国食品和药物管理局（FDA）定义的主要疗效终点是意向治疗（ITT）人群中治疗开始后 48-72 小时的早期临床反应，欧洲药品管理局（EMA）定义的主要终点是治愈测试（TOC）时研究者评估的临床成功率。非劣效性定义为疗效（头孢托罗匹酯减去万古霉素/氨曲南）成功率差异的 95%置信区间下限（CL）＞-10%。通过不良事件和实验室数据收集评估安全性。
共 679 例患者随机分为头孢托罗匹酯（n=335）或万古霉素/氨曲南（n=344）组。头孢托罗匹酯组和万古霉素/氨曲南组的早期临床成功率分别为 91.3%和 88.1%，且均显示非劣效性（校正差异：3.3%；95%CI：-1.2,7.8）。在 TOC 时，两组的临床成功率相似，且在 ITT（90.1%vs89.0%）和临床可评估人群（97.9%vs95.2%）中均显示非劣效性。两组治疗均具有相似的微生物学疗效和安全性。
TARGET 研究表明，在治疗 ABSSSIs 方面，头孢托罗匹酯与万古霉素/氨曲南相比，早期临床反应和 TOC 时的临床成功率无差异。
NCT03137173。
