舒巴坦匹酯或环丙沙星治疗女性单纯性尿路感染的随机对照 3 期临床试验
Sulopenem or Ciprofloxacin for the Treatment of Uncomplicated Urinary Tract Infections in Women: A Phase 3, Randomized Trial.
机构信息
Iterum Therapeutics, Old Saybrook, Connecticut, USA.
Das Statistical Consulting, Guerneville, California, USA.
出版信息
Clin Infect Dis. 2023 Jan 6;76(1):66-77. doi: 10.1093/cid/ciac738.
BACKGROUND
There are limited treatment options for uncomplicated urinary tract infection (uUTI) caused by resistant pathogens. Sulopenem etzadroxil/probenecid (sulopenem) is an oral thiopenem antibiotic active against multidrug-resistant pathogens that cause uUTIs.
METHODS
Patients with uUTI were randomized to 5 days of sulopenem or 3 days of ciprofloxacin. The primary endpoint was overall success, defined as both clinical and microbiologic response at day 12. In patients with ciprofloxacin-nonsusceptible baseline pathogens, sulopenem was compared for superiority over ciprofloxacin; in patients with ciprofloxacin-susceptible pathogens, the agents were compared for noninferiority. Using prespecified hierarchical statistical testing, the primary endpoint was tested in the combined population if either superiority or noninferiority was declared in the nonsusceptible or susceptible population, respectively.
RESULTS
In the nonsusceptible population, sulopenem was superior to ciprofloxacin, 62.6% vs 36.0% (difference, 26.6%; 95% confidence interval [CI], 15.1 to 7.4; P <.001). In the susceptible population, sulopenem was not noninferior to ciprofloxacin, 66.8% vs 78.6% (difference, -11.8%; 95% CI, -18.0 to 5.6). The difference was driven by a higher rate of asymptomatic bacteriuria (ASB) post-treatment in patients on sulopenem. In the combined analysis, sulopenem was noninferior to ciprofloxacin, 65.6% vs 67.9% (difference, -2.3%; 95% CI, -7.9 to 3.3). Diarrhea occurred more frequently with sulopenem (12.4% vs 2.5%).
CONCLUSIONS
Sulopenem was noninferior to ciprofloxacin in the treatment of uUTIs. Sulopenem was superior to ciprofloxacin in patients with uUTIs due to ciprofloxacin-nonsusceptible pathogens. Sulopenem was not noninferior in patients with ciprofloxacin-susceptible pathogens, driven largely by a lower rate of ASB in those who received ciprofloxacin.
CLINICAL TRIAL REGISTRATION
NCT03354598.
背景
对于由耐药病原体引起的单纯性尿路感染 (uUTI)，治疗选择有限。磺比培南乙二胺/丙磺舒（磺比培南）是一种口服噻吩培南抗生素，对引起 uUTI 的多种耐药病原体具有活性。
方法
患有 uUTI 的患者被随机分配接受 5 天的磺比培南或 3 天的环丙沙星治疗。主要终点是整体成功率，定义为第 12 天时的临床和微生物学反应。对于基线病原体对环丙沙星不敏感的患者，比较磺比培南优于环丙沙星；对于对环丙沙星敏感的病原体患者，比较两种药物的非劣效性。使用预先指定的分层统计检验，如果在不敏感或敏感人群中分别宣布了优越性或非劣效性，则对合并人群进行主要终点测试。
结果
在不敏感人群中，磺比培南优于环丙沙星，分别为 62.6%和 36.0%（差异为 26.6%；95%置信区间 [CI]，15.1 至 7.4；P <.001）。在敏感人群中，磺比培南与环丙沙星无非劣效性，分别为 66.8%和 78.6%（差异为-11.8%；95%CI，-18.0 至 5.6）。这一差异是由接受磺比培南治疗的患者治疗后无症状菌尿（ASB）的发生率更高所致。在合并分析中，磺比培南与环丙沙星无差异，分别为 65.6%和 67.9%（差异为-2.3%；95%CI，-7.9 至 3.3）。磺比培南更常引起腹泻（12.4% vs 2.5%）。
结论
磺比培南在治疗 uUTI 方面与环丙沙星不劣效。在由环丙沙星不敏感病原体引起的 uUTI 患者中，磺比培南优于环丙沙星。在对环丙沙星敏感的病原体患者中，磺比培南无非劣效性，这主要是由于接受环丙沙星治疗的患者 ASB 发生率较低所致。
临床试验注册
NCT03354598。
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