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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Out-Of-Hospital Cardiac Arrest, Pneumonia

Intervention / Treatment
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* Drug: Standard of care without prophylaxis
* Drug: Antibiotic prophylaxis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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out-of-hospital cardiac arrest, cardiac arrest, pneumonia, randomized clinical trial, infection, ceftriaxone, microbiome, inflammation, prophylaxis