Back to results

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

Primary Purpose

Out-Of-Hospital Cardiac Arrest, Pneumonia

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Standard of care without prophylaxis

Antibiotic prophylaxis

About this trial

This is an interventional prevention trial for Out-Of-Hospital Cardiac Arrest focused on measuring out-of-hospital cardiac arrest, cardiac arrest, pneumonia, randomized clinical trial, infection, ceftriaxone, microbiome, inflammation, prophylaxis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Maine Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

No prophylaxis (placebo)

Prophylaxis

Arm Description

Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection.

Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Percentage of Participants with non-pulmonary infections

ICU-free days during admission

ICU-free days in the first 28 days of admission

Mechanical ventilator-free days during admission

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

ICU Length of Stay

Intensive care unit length of stay

Hospital Length of Stay

hospital length of stay

Percentage of Participants who die in the intensive care unit

Percentage of Participants who Die in the Hospital

Percentage of Participants who Die in the Hospital during admission

Percentage of Participants Discharged Home or to Rehabilitation

Percentage of Participants Transferred to Another Hospital

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

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

Percentage of Participants with Clostridioides difficile-associated Diarrhea

Percentage of Participants with Type One Hypersensitivity Reactions

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

Percentage of Participants with Gallbladder disease

Full Information

NCT ID

NCT04999592

First Posted

July 8, 2021

Last Updated

October 2, 2023

Sponsor

David J. Gagnon

Collaborators

MaineHealth, National Institute of General Medical Sciences (NIGMS), University of New England

1. Study Identification

Unique Protocol Identification Number

NCT04999592

Brief Title

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

Acronym

PROTECT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 20, 2021 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

David J. Gagnon

Collaborators

MaineHealth, National Institute of General Medical Sciences (NIGMS), University of New England

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Out-Of-Hospital Cardiac Arrest, Pneumonia

Keywords

out-of-hospital cardiac arrest, cardiac arrest, pneumonia, randomized clinical trial, infection, ceftriaxone, microbiome, inflammation, prophylaxis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

No prophylaxis (placebo)

Arm Type

Active Comparator

Arm Description

Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection.

Arm Title

Prophylaxis

Arm Type

Experimental

Arm Description

Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days.

Intervention Type

Drug

Intervention Name(s)

Standard of care without prophylaxis

Intervention Description

Administer antibiotics in response to infection

Intervention Type

Drug

Intervention Name(s)

Antibiotic prophylaxis

Intervention Description

Ceftriaxone 2 gm IV q12h for 3 days

Primary Outcome Measure Information:

Title

Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia

Description

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

Time Frame

4 days

Secondary Outcome Measure Information:

Title

Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia

Description

Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation

Time Frame

4 days

Title

Percentage of Participants with Microbiologically-confirmed late-onset pneumonia

Description

Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation

Time Frame

≥ 4 days

Title

Percentage of Participants with Clinically-diagnosed late-onset pneumonia

Description

Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation

Time Frame

≥ 4 days

Title

Percentage of Participants with non-pulmonary infections

Description

Percentage of Participants with non-pulmonary infections

Time Frame

During the intervention and immediately after the intervention until hospital discharge, up to 6 months

Title

ICU-free days during admission

Description

ICU-free days in the first 28 days of admission

Time Frame

28 days

Title

Mechanical ventilator-free days during admission

Description

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

Time Frame

28 days

Title

ICU Length of Stay

Description

Intensive care unit length of stay

Time Frame

During the intervention and immediately after the intervention until death or ICU discharge measured in days, up to 6 months

Title

Hospital Length of Stay

Description

hospital length of stay

Time Frame

During the intervention and immediately after the intervention until death or hospital discharge measured in days, up to 6 months

Title

Percentage of Participants who die in the intensive care unit

Description

Percentage of Participants who die in the intensive care unit

Time Frame

During the intervention and immediately after the intervention until death or ICU discharge

Title

Percentage of Participants who Die in the Hospital

Description

Percentage of Participants who Die in the Hospital during admission

Time Frame

During the intervention and immediately after the intervention until death or hospital discharge

Title

Percentage of Participants Discharged Home or to Rehabilitation

Description

Percentage of Participants Discharged Home or to Rehabilitation

Time Frame

During the intervention and immediately after the intervention until death or hospital discharge

Title

Percentage of Participants Transferred to Another Hospital

Description

Percentage of Participants Transferred to Another Hospital

Time Frame

During the intervention and immediately after the intervention until death or hospital transfer

Title

Percentage of Participants with a Good Functional Outcome at Hospital Discharge

Description

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

Time Frame

After the intervention at the time the participant is discharged from the hospital

Title

13. Percentage of Participants with a Good Functional Outcome at 6 Months Post-hospital Discharge

Description

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

Time Frame

6 months post-hospital discharge

Title

Percentage of Participants with Clostridioides difficile-associated Diarrhea

Description

Percentage of Participants with Clostridioides difficile-associated Diarrhea

Time Frame

During the intervention and immediately after the intervention until death or hospital discharge

Title

Percentage of Participants with Type One Hypersensitivity Reactions

Description

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

Time Frame

Three days

Title

Percentage of Participants with Gallbladder disease

Description

Percentage of Participants with Gallbladder disease

Time Frame

During the intervention and immediately after the intervention until death or hospital discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

David Gagnon, PharmD

Phone

207-662-1338

dgagnon@mmc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Christine Lord, BSN, RN

Phone

207-662-5432

Facility Information:

Facility Name

Maine Medical Center

City

Portland

State/Province

Maine

ZIP/Postal Code

04102

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Gagnon, PharmD

Phone

207-662-1338

Dgagnon@mmc.org

First Name & Middle Initial & Last Name & Degree

Christine Lord, BSN, RN

Phone

207-662-5432

LordC@mmc.org

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35246202

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs