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

Autor: Gagnon DJ; Department of Pharmacy, Maine Medical Center, Portland, ME, USA. dgagnon@mmc.org.; Maine Medical Center Research Institute, Scarborough, ME, USA. dgagnon@mmc.org.; Tufts University School of Medicine, Boston, MA, USA. dgagnon@mmc.org., Ryzhov SV; Maine Medical Center Research Institute, Scarborough, ME, USA., May MA; University of New England College of Osteopathic Medicine, Biddeford, ME, USA., Riker RR; Tufts University School of Medicine, Boston, MA, USA.; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., Geller B; Tufts University School of Medicine, Boston, MA, USA.; Maine Medical Partners, MaineHealth Cardiology, Scarborough, ME, USA., May TL; Maine Medical Center Research Institute, Scarborough, ME, USA.; Tufts University School of Medicine, Boston, MA, USA.; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., Bockian S; Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA., deKay JT; Maine Medical Center Research Institute, Scarborough, ME, USA., Eldridge A; Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA., Van der Kloot T; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., Lerwick P; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., Lord C; Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA., Lucas FL; Maine Medical Center Research Institute, Scarborough, ME, USA., Mailloux P; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., McCrum B; Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA., Searight M; Maine Medical Center Neuroscience Institute, Maine Medical Center, Portland, ME, USA., Wirth J; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA., Zuckerman J; Tufts University School of Medicine, Boston, MA, USA., Sawyer D; Maine Medical Center Research Institute, Scarborough, ME, USA.; Maine Medical Partners, MaineHealth Cardiology, Scarborough, ME, USA., Seder DB; Maine Medical Center Research Institute, Scarborough, ME, USA.; Tufts University School of Medicine, Boston, MA, USA.; Department of Critical Care Services, Maine Medical Center, Portland, ME, USA.
Jazyk: angličtina
Zdroj: Trials [Trials] 2022 Mar 04; Vol. 23 (1), pp. 197. Date of Electronic Publication: 2022 Mar 04.
DOI: 10.1186/s13063-022-06127-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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