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

• Published in: Current controlled trials in cardiovascular medicine Vol. 23; no. 1; pp. 197 - 13
• Main Authors: Gagnon, David J., Ryzhov, Sergey V., May, Meghan A., Riker, Richard R., Geller, Bram, May, Teresa L., Bockian, Sarah, deKay, Joanne T., Eldridge, Ashley, Van der Kloot, Thomas, Lerwick, Patricia, Lord, Christine, Lucas, F. Lee, Mailloux, Patrick, McCrum, Barbara, Searight, Meghan, Wirth, Joel, Zuckerman, Jonathan, Sawyer, Douglas, Seder, David B.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.03.2022; BioMed Central; BMC
• Subjects: Antibiotics; Bacteria; Bacterial infections; Bacterial pneumonia; Cardiac arrest; Cardiology; Ceftriaxone; Ceftriaxone - adverse effects; Ceftriaxone sodium; Complications and side effects; Corporate sponsorship; Critical care; Dosage and administration; Double-Blind Method; Emergency medical care; Hospitals; Humans; Hypothermia; Inflammation; Informed consent; Medicine; Mortality; Neurosciences; Ostomy; Out-of-Hospital Cardiac Arrest - diagnosis; Out-of-Hospital Cardiac Arrest - drug therapy; Patients; Pneumonia; Prevention; Randomized Controlled Trials as Topic; Research centers; Risk factors; Staphylococcus infections; Streptococcus infections; Study Protocol; Targeted temperature management; Testing; Treatment Outcome; United States; United States > US; Maine; Metagenomics; Pneumonia; Antibiotics; Cardiac arrest; Inflammation; Ceftriaxone; Hypothermia; Microbiome; Targeted temperature management
• ISSN: 1745-6215; 1745-6215
• 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.