Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.

中文翻译：

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IC43重组铜绿假单胞菌疫苗对机械通气重症监护患者的疗效、免疫原性和安全性——一项随机临床试验

铜绿假单胞菌感染是重症监护病房 (ICU) 的严重威胁。这项验证性、随机、多中心、安慰剂对照、双盲、2/3 期研究的目的是评估 IC43 重组铜绿假单胞菌疫苗在非手术 ICU 患者中的疗效、免疫原性和安全性。800 名 18 至 80 岁入住 ICU 且预期需要机械通气 ≥ 48 小时的患者按 1:1 随机分配至 IC43 100 μg 或生理盐水安慰剂组，间隔 7 天接种两次疫苗。主要疗效终点是首次接种疫苗后 28 天患者的全因死亡率。还评估了免疫原性和安全性。在第 28 天，IC43 和安慰剂组的全因死亡率分别为 29.2% 和 27.7%（P = .67）。总生存期（Kaplan-Meier 生存期估计值，P = .46）和确诊 ≥ 1 例铜绿假单胞菌侵袭性感染或呼吸道感染的患者比例在两组之间也没有显着差异。OprF/I 滴度的几何平均倍数在第一次接种后增加了 1.5 倍，在第二次接种后第 28 天增加了 20 倍，在第 180 天增加了 2.9 倍。安慰剂组中明显更多的患者 (96.5%) 发生≥ 一个不良事件（ AE) 与 IC43 100 μg 组 (93.1%) (P = .04)。IC43 和安慰剂组中最常报告的严重 AE 是呼吸衰竭（分别为 6.9% 对 5.7%）、感染性休克（4.1% 对 6.5%）、心脏骤停（4.3% 对 5.7%）、多器官衰竭（4.6%） 5.5%）和败血症（4.6% 对 4.2%）。在 IC43 组中没有报告相关的严重 AE。IC43 100 μg 疫苗在这一庞大的医学疾病、机械通气患者群体中具有良好的耐受性。该疫苗实现了高免疫原性，但在总体死亡率方面没有提供优于安慰剂的临床益处。https://clinicaltrials.gov (NCT01563263)。注册于 2012 年 3 月 14 日发送至 ClinicalTrials.gov，但​​由 ClinicalTrials.gov 于 2012 年 3 月 26 日发布。第一个受试者于 2012 年 3 月 22 日纳入试验。