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

Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT): a Randomized-controlled Trial and Microbiome Assessment

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.

Study Overview

• Status: Recruiting
• Conditions: Pneumonia; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Drug: Standard of care without prophylaxis; Drug: Antibiotic prophylaxis

Detailed Description

Pneumonia is an infection of the lungs resulting in alveolar inflammation and fluid or purulent material accumulation. It is the most common infection after cardiac arrest occurring in up to 65% of patients treated with targeted temperature management. Pneumonia may result from aspiration during cardiopulmonary resuscitation (CPR), or by introduction of oropharyngeal flora into the lungs during airway management. Preventing infection after OHCA may: 1) reduce exposure to broad-spectrum antibiotics and subsequent collateral damage, 2) prevent hemodynamic derangements due to local and systemic inflammation, and 3) prevent an association between infection and morbidity and mortality. These benefits must be balanced with the risk for altering bacterial resistomes in the absence clinical infection. Accordingly, further study is warranted to understand the risk-to-benefit ratio of prophylactic antibiotics.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Gagnon, PharmD; Phone Number: 207-662-1338; Email: Dgagnon@mmc.org
• Study Contact Backup: Name: Christine Lord, BSN, RN; Phone Number: 207-662-5432

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Recruiting
      • Maine Medical Center
      • Contact: David Gagnon, PharmD; Phone Number: 207-662-1338; Email: Dgagnon@mmc.org
      • Contact: Christine Lord, BSN, RN; Phone Number: 207-662-5432; Email: LordC@mmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No prophylaxis (placebo); Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection.	Drug: Standard of care without prophylaxis; Administer antibiotics in response to infection
Experimental: Prophylaxis; Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days.	Drug: Antibiotic prophylaxis; Ceftriaxone 2 gm IV q12h for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia	Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation	4 days
Percentage of Participants with Microbiologically-confirmed late-onset pneumonia	Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation	≥ 4 days
Percentage of Participants with Clinically-diagnosed late-onset pneumonia	Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation	≥ 4 days
Percentage of Participants with non-pulmonary infections	Percentage of Participants with non-pulmonary infections	During the intervention and immediately after the intervention until hospital discharge, up to 6 months
ICU-free days during admission	ICU-free days in the first 28 days of admission	28 days
Mechanical ventilator-free days during admission	Mechanical ventilator-free days in the first 28 days of admission	28 days
ICU Length of Stay	Intensive care unit length of stay	During the intervention and immediately after the intervention until death or ICU discharge measured in days, up to 6 months
Hospital Length of Stay	hospital length of stay	During the intervention and immediately after the intervention until death or hospital discharge measured in days, up to 6 months
Percentage of Participants who die in the intensive care unit	Percentage of Participants who die in the intensive care unit	During the intervention and immediately after the intervention until death or ICU discharge
Percentage of Participants who Die in the Hospital	Percentage of Participants who Die in the Hospital during admission	During the intervention and immediately after the intervention until death or hospital discharge
Percentage of Participants Discharged Home or to Rehabilitation	Percentage of Participants Discharged Home or to Rehabilitation	During the intervention and immediately after the intervention until death or hospital discharge
Percentage of Participants Transferred to Another Hospital	Percentage of Participants Transferred to Another Hospital	During the intervention and immediately after the intervention until death or hospital transfer
Percentage of Participants with a Good Functional Outcome at Hospital Discharge	Percentage of Participants with a Good Functional Outcome at Hospital Discharge Good functional outcome will be mRS ≤0-3 of or a CPC 1-2	After the intervention at the time the participant is discharged from the hospital
13. Percentage of Participants with a Good Functional Outcome at 6 Months Post-hospital Discharge	13. Percentage of Participants with a Good Functional Outcome at 6 Months Post-hospital Discharge. Good functional outcome will be mRS ≤0-3 of or a CPC 1-2	6 months post-hospital discharge
Percentage of Participants with Clostridioides difficile-associated Diarrhea	Percentage of Participants with Clostridioides difficile-associated Diarrhea	During the intervention and immediately after the intervention until death or hospital discharge
Percentage of Participants with Type One Hypersensitivity Reactions	Percentage of Participants with Type One (immediate-type) hypersensitivity reactions	Three days
Percentage of Participants with Gallbladder disease	Percentage of Participants with Gallbladder disease	During the intervention and immediately after the intervention until death or hospital discharge

Collaborators and Investigators

• Sponsor: David J. Gagnon
• Collaborators: National Institute of General Medical Sciences (NIGMS); University of New England; MaineHealth

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: infection; prophylaxis; inflammation; pneumonia; cardiac arrest; microbiome; randomized clinical trial; out-of-hospital cardiac arrest; ceftriaxone
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Heart Arrest; Out-of-Hospital Cardiac Arrest; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 1P20GM139745-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No