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Selected Works of David B Seder, MD
Article
Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT): study protocol for a randomized, placebo-controlled trial
Trials
  • David J Gagnon, Maine Medical Center
  • Sergey V Ryzhov, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • Meghan A May, University of New England College of Osteopathic Medicine, Biddeford, ME, USA.
  • Richard R Riker, Tufts University School of Medicine, Boston, MA, USA.
  • Bram Geller, Tufts University School of Medicine, Boston, MA, USA.
  • Teresa L May, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • Sarah Bockian, Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA.
  • Joanne T deKay, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • Ashley Eldridge, Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA.
  • Thomas Van der Kloot, Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
  • Patricia Lerwick, Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
  • Christine Lord, Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA.
  • F Lee Lucas, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • Patrick Mailloux, Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
  • Barbara McCrum, Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA.
  • Meghan Searight, Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA.
  • Joel Wirth, Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
  • Jonathan Zuckerman, Tufts University School of Medicine, Boston, MA, USA.
  • Douglas Sawyer, Maine Medical Center Research Institute, Scarborough, ME, USA.
  • David B Seder, Maine Medical Center Research Institute, Scarborough, ME, USA.
Link
Document Type
Article
Publication Date
3-4-2022
Institution/Department
Pharmacy; Pulmonology; MaineHealth Institute for Research
MeSH Headings
Ceftriaxone (adverse effects); Double-Blind Method; Humans; Inflammation; Out-of-Hospital Cardiac Arrest (diagnosis, drug therapy); Pneumonia; Randomized Controlled Trials as Topic; Treatment Outcome
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.

Citation Information
Gagnon DJ, Ryzhov SV, May MA, et al. Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial. Trials. 2022;23(1):197. Published 2022 Mar 4. doi:10.1186/s13063-022-06127-w