Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
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
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with 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
- Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia [4 days]
Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation
- Percentage of Participants with Microbiologically-confirmed late-onset pneumonia [≥ 4 days]
Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
- Percentage of Participants with Clinically-diagnosed late-onset pneumonia [≥ 4 days]
Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
- Percentage of Participants with 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
- ICU Length of Stay [During the intervention and immediately after the intervention until death or ICU discharge measured in days, up to 6 months]
Intensive care unit 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]
hospital length of stay
- 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 intensive care unit
- Percentage of Participants who Die in the Hospital [During the intervention and immediately after the intervention until death or hospital discharge]
Percentage of Participants who Die in the Hospital during admission
- Percentage of Participants Discharged Home or to Rehabilitation [During the intervention and immediately after the intervention until death or hospital discharge]
Percentage of Participants Discharged Home or to Rehabilitation
- Percentage of Participants Transferred to Another Hospital [During the intervention and immediately after the intervention until death or hospital transfer]
Percentage of Participants Transferred to Another Hospital
- Percentage of Participants with a Good Functional Outcome at Hospital Discharge [After the intervention at the time the participant is discharged from the hospital]
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
- 13. Percentage of Participants with a Good Functional Outcome at 6 Months Post-hospital Discharge [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
- 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 Clostridioides difficile-associated Diarrhea
- Percentage of Participants with Type One Hypersensitivity Reactions [Three days]
Percentage of Participants with Type One (immediate-type) hypersensitivity reactions
- Percentage of Participants with Gallbladder disease [During the intervention and immediately after the intervention until death or hospital discharge]
Percentage of Participants with Gallbladder disease
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Maine Medical Center | Portland | Maine | United States | 04102 |
Sponsors and Collaborators
- David J. Gagnon
- MaineHealth
- National Institute of General Medical Sciences (NIGMS)
- University of New England
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1P20GM139745-01