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

Phase 2

Terminated

Conditions: Out-Of-Hospital Cardiac Arrest
Pneumonia

Interventions: Drug: Standard of care without prophylaxis
Drug: Antibiotic prophylaxis

Registration Number: NCT04999592

Lead Sponsor: David J. Gagnon

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 53

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
No prophylaxis (placebo)	Standard of care without prophylaxis	Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection.
Prophylaxis	Antibiotic prophylaxis	Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Microbiologically-confirmed Early-onset Pneumonia	4 days	Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring \<4 days after initiation of mechanical ventilation
Microbiologically-confirmed Late-onset Pneumonia	≥ 4 days	Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
Clinically-diagnosed Late-onset Pneumonia	≥ 4 days	Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
Non-pulmonary Infections	During the intervention and immediately after the intervention until hospital discharge, up to 6 months	Percentage of Participants with non-pulmonary infections
ICU-free Days During Admission	28 days	ICU-free days in the first 28 days of admission
Mechanical Ventilator-free Days During Admission	28 days	Mechanical ventilator-free days in the first 28 days of admission
Death in the Hospital	During the intervention (3 days) and immediately after the intervention until subject death or hospital discharge, an average of 30 days	Percentage of Participants who Die in the Hospital during admission
Functional Outcome at 6 Months Post-hospital Discharge	6 months post-hospital discharge	Median mRS (0 as no residual symptoms and 6 as death) at 6 Months Post-hospital Discharge
Clostridioides Difficile-associated Diarrhea	During the intervention and immediately after the intervention until death or hospital discharge	Percentage of Participants with Clostridioides difficile-associated Diarrhea
Type One Hypersensitivity Reactions	Three days	Percentage of Participants with Type One (immediate-type) hypersensitivity reactions
Participants With Gallbladder Disease	During the intervention and immediately after the intervention until death or hospital discharge	Percentage of Participants with Gallbladder disease