Trials (Mar 2022)

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial

  • David J. Gagnon,
  • Sergey V. Ryzhov,
  • Meghan A. May,
  • Richard R. Riker,
  • Bram Geller,
  • Teresa L. May,
  • Sarah Bockian,
  • Joanne T. deKay,
  • Ashley Eldridge,
  • Thomas Van der Kloot,
  • Patricia Lerwick,
  • Christine Lord,
  • F. Lee Lucas,
  • Patrick Mailloux,
  • Barbara McCrum,
  • Meghan Searight,
  • Joel Wirth,
  • Jonathan Zuckerman,
  • Douglas Sawyer,
  • David B. Seder

DOI
https://doi.org/10.1186/s13063-022-06127-w
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 13

Abstract

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Abstract Background 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. Methods 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. Discussion 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. Trial registration ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

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