Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT)

NCT04999592 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1P20GM139745-01P20GM139745
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized-controlled trial and microbiome assessment to understand the risk-to-benefit ratio of prophylactic antibiotics (Ceftriaxone) vs placebo in patients with pneumonia and inflammation after cardiac arrest outside the hospital.

Conditions

Out-Of-Hospital Cardiac Arrest; Pneumonia

Keywords

out-of-hospital cardiac arrest; cardiac arrest; pneumonia; randomized clinical trial; infection; ceftriaxone; microbiome; inflammation; prophylaxis

Outcome Measures

Primary Outcomes (1)

• Clinically-diagnosed Early-onset Pneumonia

  Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia occurring \<4 days after initiation of mechanical ventilation

  4 days

Secondary Outcomes (11)

• Microbiologically-confirmed Early-onset Pneumonia

  4 days

• Microbiologically-confirmed Late-onset Pneumonia

  ≥ 4 days

• Clinically-diagnosed Late-onset Pneumonia

  ≥ 4 days

• Non-pulmonary Infections

  During the intervention and immediately after the intervention until hospital discharge, up to 6 months

• ICU-free Days During Admission

  28 days

Study Arms (2)

No prophylaxis (placebo)

ACTIVE COMPARATOR

Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection.

Drug: Standard of care without prophylaxis

Prophylaxis

EXPERIMENTAL

Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days.

Drug: Antibiotic prophylaxis

Interventions

Standard of care without prophylaxis DRUG

Administer antibiotics in response to infection

Also known as: Placebo

No prophylaxis (placebo)

Antibiotic prophylaxis DRUG

Ceftriaxone 2 gm IV q12h for 3 days

Also known as: Rocephin (ceftriaxone)

Prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• Comatose (do not follow simple verbal commands)
• Have any initial heart rhythm (shockable or non-shockable)
• OHCA including the emergency department

You may not qualify if:

• Name on opt-out list
• In-hospital cardiac arrest
• Interval \>6 hours from ICU admission to study drug receipt
• Preexisting terminal disease making 180-day survival unlikely
• Refused informed consent
• Emergent coronary artery bypass grafting
• Anaphylaxis or angioedema to beta-lactam antibiotics (i.e., cephalosporins or penicillins)
• Under legal guardianship or prisoner
• Known colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE)
• Clinical bacterial infection prior to hospital admission defined as any one of the following:
• Infectious prodrome preceding OHCA
• Active course of antibiotics for infection prior to admission
• Active infection documented in the electronic medical record
• Family or surrogate endorsement of an active infection

Sponsors & Collaborators

• David J. Gagnon: lead
• MaineHealth: collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator
• University of New England: collaborator

Study Sites (1)

Maine Medical Center

Portland, Maine, 04102, United States

Location

Related Publications (2)

• Gagnon DJ, Ryzhov SV, May MA, Riker RR, Geller B, May TL, Bockian S, deKay JT, Eldridge A, Van der Kloot T, Lerwick P, Lord C, Lucas FL, Mailloux P, McCrum B, Searight M, Wirth J, Zuckerman J, Sawyer D, Seder DB. Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial. Trials. 2022 Mar 4;23(1):197. doi: 10.1186/s13063-022-06127-w.

  PMID: 35246202 BACKGROUND

• Gagnon DJ, Burkholder KM, Weissman AJ, Riker RR, Ryzhov S, May TL, DiPalazzo J, deKay JT, Knudsen L, Moore MW, Pozzessere NA, Weatherbee M, Kelly M, Nigatu AS, Sevigny JL, Simpson S, Thomas WK, Callaway CW, Geller BJ, Sawyer DB, Seder DB. Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT). Chest. 2026 Jan;169(1):115-127. doi: 10.1016/j.chest.2025.08.007. Epub 2025 Aug 28.

  PMID: 40885534 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Pneumonia; Heart Arrest; Infections; Inflammation

Interventions

Standard of Care; Antibiotic Prophylaxis; Ceftriaxone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Chemoprevention; Drug Therapy; Therapeutics; Premedication; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David J. Gagnon, PharmD - Principal Investigator
• Organization: MaineHealth Maine Medical Center - Portland

dgagnon@mmc.org

207-662-0111

Study Officials

• David Gagnon, PharmD

  MaineHealth

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The clinical team responsible for the participant (physicians, nurses and others) and involved with direct patient care will be blinded. Investigators will be blinded and the placebo will match the study drug. Outcomes Assessors will be blinded to treatment assignment during assessments of pneumonia and functional outcome.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Critical Care Clinical Pharmacist

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: August 11, 2021
• Study Start: August 20, 2021
• Primary Completion: March 1, 2024
• Study Completion: November 1, 2024
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)