Clinical trial NCT04999592: Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT)
Official title: Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT): a Randomized-controlled Trial and Microbiome Assessment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Out-Of-Hospital Cardiac Arrest
Pneumonia
Keywords: out-of-hospital cardiac arrest
cardiac arrest
pneumonia
randomized clinical trial
infection
ceftriaxone
microbiome
inflammation
prophylaxis
Lead sponsor: MaineHealth
Sponsor class: OTHER
Collaborators: name: MaineHealth
name: National Institute of General Medical Sciences (NIGMS)
name: University of New England
First posted: 2021-08-11
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Clinically-diagnosed Early-onset Pneumonia
timeFrame: 4 days
Secondary outcomes:
measure: Microbiologically-confirmed Early-onset Pneumonia
timeFrame: 4 days
measure: Microbiologically-confirmed Late-onset Pneumonia
timeFrame: ≥ 4 days
measure: Clinically-diagnosed Late-onset Pneumonia
timeFrame: ≥ 4 days
measure: Non-pulmonary Infections
timeFrame: During the intervention and immediately after the intervention until hospital discharge, up to 6 months
measure: ICU-free Days During Admission
timeFrame: 28 days
measure: Mechanical Ventilator-free Days During Admission
timeFrame: 28 days
measure: Death in the Hospital
timeFrame: During the intervention (3 days) and immediately after the intervention until subject death or hospital discharge, an average of 30 days
measure: Functional Outcome at 6 Months Post-hospital Discharge
timeFrame: 6 months post-hospital discharge
measure: Clostridioides Difficile-associated Diarrhea
timeFrame: During the intervention and immediately after the intervention until death or hospital discharge
measure: Type One Hypersensitivity Reactions
timeFrame: Three days
measure: Participants With Gallbladder Disease
timeFrame: During the intervention and immediately after the intervention until death or hospital discharge
Other outcomes:
Locations:
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
Study officials:
affiliation: MaineHealth
name: David Gagnon, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.