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

Sponsor
David J. Gagnon (Other)
Overall Status
Recruiting
CT.gov ID
NCT04999592
Collaborator
MaineHealth (Other), National Institute of General Medical Sciences (NIGMS) (NIH), University of New England (Other)
120
1
2
34.3
3.5

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

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The clinical team responsible for the participant (physicians, nurses and others) and involved with direct patient care will be blinded. Investigators will be blinded and the placebo will match the study drug. Outcomes Assessors will be blinded to treatment assignment during assessments of pneumonia and functional outcome.
Primary Purpose:
Prevention
Official Title:
Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT): a Randomized-controlled Trial and Microbiome Assessment
Actual Study Start Date :
Aug 20, 2021
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Jun 30, 2024

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

  1. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. ICU-free days during admission [28 days]

    ICU-free days in the first 28 days of admission

  6. Mechanical ventilator-free days during admission [28 days]

    Mechanical ventilator-free days in the first 28 days of admission

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Percentage of Participants with Type One Hypersensitivity Reactions [Three days]

    Percentage of Participants with Type One (immediate-type) hypersensitivity reactions

  17. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
David J. Gagnon, Critical Care Clinical Pharmacist, MaineHealth
ClinicalTrials.gov Identifier:
NCT04999592
Other Study ID Numbers:
  • 1P20GM139745-01
First Posted:
Aug 11, 2021
Last Update Posted:
Sep 8, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by David J. Gagnon, Critical Care Clinical Pharmacist, MaineHealth
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 8, 2021