Department of Pharmacy, Maine Medical Center, Portland, ME, USA.
Maine Medical Center Research Institute, Scarborough, ME, USA.
Trials. 2022 Mar 4;23(1):197. doi: 10.1186/s13063-022-06127-w.
Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.
The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years.
The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome.
ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.
肺炎是院外心脏骤停（OHCA）后最常见的感染，多达 65%的自主循环恢复后仍处于昏迷状态的患者会发生肺炎。预防 OHCA 后感染可能（1）减少广谱抗生素的暴露，（2）预防局部和全身炎症引起的血流动力学紊乱，以及（3）预防感染相关的发病率和死亡率。
头孢曲松预防心脏骤停后肺炎和炎症的试验（PROTECT）是一项在美国缅因州波特兰的缅因州医疗中心进行的随机、安慰剂对照、单中心、四盲（患者、治疗团队、研究团队、结局评估者）、非商业性、优效性试验。头孢曲松 2g 静脉注射，每 12 小时 1 次，连用 3 天，与匹配的安慰剂进行比较。主要疗效结局是机械通气开始后<4 天发生的早发性肺炎的发生率。同时，将检查 T 细胞介导的炎症细菌耐药组。安全性结局包括 1 型即刻型过敏反应、胆囊损伤和艰难梭菌相关性腹泻的发生率。该试验将在大约 3 到 4 年内招募 120 名受试者。
PROTECT 试验具有创新性，（1）纳入了无论初始心律如何的 OHCA 幸存者，（2）使用了一种在美国可用的低风险抗生素，该抗生素以前未在 OHCA 后进行过测试，（3）纳入了头孢曲松的抗炎作用作为改善临床结局的新机制，以及（4）在使用头孢曲松预防之前和之后，对细菌耐药组进行了全面的宏基因组评估。长期目标是开展一项有死亡或功能结局的 III 期确证试验。
ClinicalTrials.gov NCT04999592。于 2021 年 8 月 10 日注册。
