Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial.

We sought to identify the effect of endotoxin removal from the blood with polymyxin B haemoadsorption on mortality.

我们试图确定使用多粘菌素B血液吸附去除血液中内毒素对死亡率的影响。

Methods

We conducted an open-label, randomised, controlled, phase 3 trial at 19 US hospitals, enrolling adults (aged ≥18 years) with septic shock requiring vasopressors, with multiple organ dysfunction, and with endotoxin activity between 0·60 and 0·89 units.

我们在19家美国医院开展了一项开放标签、随机对照的III期试验，招募了需要使用血管加压药物、具有多器官功能障碍、内毒素活性在0.60至0.89单位之间的成年（≥18岁）脓毒性休克患者。

Patients were randomly assigned (2:1) to receive two sessions of polymyxin B plus standard of care or standard of care alone (control), with block randomisation stratified by site.

患者按2:1的比例随机分配接受两轮多粘菌素B联合标准治疗或仅接受标准治疗（对照组），按地点分层的块随机化分组。

Study personnel were masked to treatment allocation.

研究人员对治疗分配情况进行了盲法处理。

Polymyxin B haemoadsorption was given via haemodialysis at a blood flow rate of 80-120 mL/min for 90-120 min per session, 22 h apart.

通过血液透析，以80-120毫升/分钟的血流速度进行多粘菌素B血液吸附治疗，每次治疗持续90-120分钟，两次治疗间隔22小时。

The primary outcome was 28-day mortality in the intention-to-treatcohort.

主要结果是意向治疗队列中的28天死亡率。

The safety cohort included all participants exposed to any amount of study treatment.

安全性队列包括所有接受过任何量研究治疗的参与者。

Design and analysis followed a Bayesian framework, using a prior for the treatment effect based on a subgroup of the earlier EUPHRATES trial. 90-day mortality was the key secondary outcome.

设计和分析遵循贝叶斯框架，使用基于早期EUPHRATES试验子组的治疗效果先验。90天死亡率是关键次要结果。

The trial was registered at ClinicalTrials.gov and is completed (NCT03901807).

该试验已在ClinicalTrials.gov注册并完成（NCT03901807）。

Results

Between Sept 30, 2019, and April 10, 2025, we screened 14 890 patients, of whom 157 were enrolled (106 assigned to polymyxin B and 51 to control; 66 [42%] women and 91 [58%] men).

在2019年9月30日至2025年4月10日期间，我们筛查了14,890名患者，其中157名被纳入研究（106名被分配至多粘菌素B组，51名被分配至对照组；66名[42%]女性和91名[58%]男性）。

At 28 days, 41 (39%) patients in the polymyxin B group and 23 (45%) in the control group had died, yielding a posterior probability of benefit of 95·3% (APACHE-II adjusted odds ratio 0·67 [95% credible interval 0·39-1·08]).

在28天时，多粘菌素B组有41名（39%）患者死亡，对照组有23名（45%）患者死亡，得出的后验概率为95.3%（APACHE-II调整后的优势比为0.67 [95%可信区间0.39-1.08]）。

At 90 days, the posterior probability of benefit was 99·4% (0·54 [0·32-0·87]).

在90天时，受益的后验概率为99.4%（0.54 [0.32-0.87]）。

Of 100 patients in the polymyxin B group assessed for safety, 30 (30%) had a serious adverse eventcompared with 11 (22%) of 51 patients in the control group (difference -8 percentage points [95% CI -22 to 6]).

在评估安全性的多粘菌素B组100名患者中，有30名（30%）发生了严重不良事件，而在对照组的51名患者中，有11名（22%）发生了严重不良事件（差异为-8个百分点[95%置信区间-22至6]）。

Two (2%) serious adverse events in the polymyxin B group were treatment-related, one related to polymyxin B and one to catheter placement.

在多粘菌素B组中有2例（2%）严重不良事件与治疗相关，一例与多粘菌素B相关，另一例与导管放置相关。

interpretation

In patients with endotoxic septic shock defined by high endotoxin activity and multiorgan failure, polymyxin B haemoadsorption was associated with a high probability of lower mortality at 28 days and 90 days.

在被高内毒素活性和多器官衰竭定义的内毒素性休克患者中，多粘菌素B血液吸附与28天和90天较低死亡率的高概率相关。

funding

Spectral Medical.

光谱医疗公司。