三叶草（艰难梭菌疫苗疗效试验）研究：一项3期随机试验，调查一种脱毒毒素A/B疫苗在50岁及以上艰难梭菌感染风险增加的成年人中的疗效和安全性。
CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection.
作者信息
Donskey Curtis J, Dubberke Erik R, Klein Nicola P, Liles Elizabeth G, Szymkowiak Katarzyna, Wilcox Mark H, Lawrence Jody, Bouguermouh Salim, Zhang Haiying, Koury Kenneth, Bailey Ruth, Smith Helen M, Lockhart Stephen, Lamberth Erik, Kalina Warren V, Pride Michael W, Webber Chris, Anderson Annaliesa S, Jansen Kathrin U, Gruber William C, Kitchin Nicholas
机构信息
Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Division of Infectious Diseases, Washington University in St. Louis, St. Louis, Missouri, USA.
出版信息
Clin Infect Dis. 2024 Dec 17;79(6):1503-1511. doi: 10.1093/cid/ciae410.
BACKGROUND
Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.
METHODS
This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed.
RESULTS
The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], -38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, -28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P = .02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups.
CONCLUSIONS
Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden.
CLINICAL TRIALS REGISTRATION
NCT03090191.
背景
艰难梭菌感染（CDI）会导致大量死亡和医疗负担。我们评估了用于预防原发性CDI的去毒毒素A/B PF-06425090疫苗。
方法
这项3期观察者盲法研究将≥50岁且CDI风险增加的人群（N = 17535）随机（1:1）分为两组，分别接受3剂PF-06425090或安慰剂（0、1和6个月）。主要终点是在第3剂后≥14天（PD3；第一个主要终点）和第2剂后≥14天（PD2；第二个主要终点）出现首次CDI发作（24小时内≥3次不成形大便；中心实验室确认毒素A/B阳性）。评估了CDI持续时间、CDI相关医疗护理需求（次要终点）以及PD3时的抗生素使用情况（事后分析）。评估了耐受性和安全性。
结果
未达到主要终点（17名PF-06425090接受者和25名安慰剂接受者在PD3≥14天后出现首次CDI发作[疫苗效力（VE）= 31.0%（96.4%置信区间[CI]，-38.7%至66.6%）]；24名PF-06425090接受者和34名安慰剂接受者在PD2≥14天后出现首次CDI发作[VE = 28.6%（96.4% CI，-28.4%至61.0%）]。PF-06425090组的CDI持续时间中位数（1天）低于安慰剂组（4天；双侧名义P = 0.02）。在首次出现CDI发作的参与者中，0名PF-06425090接受者和11名安慰剂接受者寻求CDI相关医疗护理（事后分析估计VE = 100%；95% CI，59.6%至100.0%），0名PF-06425090接受者和10名安慰剂接受者需要抗生素治疗（VE = 100%；95% CI，54.8%至100.0%）。PF-06425090接受者的局部反应更频繁，两组间全身事件总体相似；大多数为轻至中度。两组间不良事件发生率相似。
结论
3剂PF-06425090安全且耐受性良好。虽然未达到主要终点，但PF-06425090缩短了症状持续时间、减少了需要医疗护理的CDI以及针对CDI的抗生素治疗，突出了其减轻CDI相关医疗负担的潜力。
临床试验注册号
NCT03090191。
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