Out-Of-Hospital Cardiac ArrestPhase 2PROTECTNCT04999592
Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT)
A Phase 2 study testing Antibiotic prophylaxis in people with Out-Of-Hospital Cardiac Arrest and Pneumonia, run by David J. Gagnon at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Out-Of-Hospital Cardiac Arrest, Pneumonia
- What is being tested?
- Antibiotic prophylaxis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2021to 1 Nov 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT): a Randomized-controlled Trial and Microbiome Assessment
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.
Read the 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.
- Conditions
- Out-Of-Hospital Cardiac Arrest, Pneumonia
- Being tested
- Standard of care without prophylaxis, Antibiotic prophylaxis
- Keywords
- out-of-hospital cardiac arrest, cardiac arrest, pneumonia, randomized clinical trial, infection, ceftriaxone, microbiome, inflammation, prophylaxis
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Pneumonia, Heart Arrest, Infections, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of care without prophylaxisDrug
Also called Placebo
Administer antibiotics in response to infection
Antibiotic prophylaxisDrug
Also called Rocephin (ceftriaxone)
Ceftriaxone 2 gm IV q12h for 3 days
| Study group | Role | What they receive |
|---|---|---|
| No prophylaxis (placebo) | Active comparator | Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted.
Administer antibiotics in response to infection. Receives: Drug: Standard of care without prophylaxis |
| Prophylaxis | Experimental | Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. Receives: Drug: Antibiotic prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinically-diagnosed Early-onset Pneumonia
Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation
Measured: 4 days
Secondary outcomes (11)
Microbiologically-confirmed Early-onset Pneumonia
Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation
Measured: 4 days
Microbiologically-confirmed Late-onset Pneumonia
Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
Measured: ≥ 4 days
Clinically-diagnosed Late-onset Pneumonia
Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation
Measured: ≥ 4 days
Non-pulmonary Infections
Percentage of Participants with non-pulmonary infections
Measured: During the intervention and immediately after the intervention until hospital discharge, up to 6 months
ICU-free Days During Admission
ICU-free days in the first 28 days of admission
Measured: 28 days
Mechanical Ventilator-free Days During Admission
Mechanical ventilator-free days in the first 28 days of admission
Measured: 28 days
Death in the Hospital
Percentage of Participants who Die in the Hospital during admission
Measured: During the intervention (3 days) and immediately after the intervention until subject death or hospital discharge, an average of 30 days
Functional Outcome at 6 Months Post-hospital Discharge
Median mRS (0 as no residual symptoms and 6 as death) at 6 Months Post-hospital Discharge
Measured: 6 months post-hospital discharge
Clostridioides Difficile-associated Diarrhea
Percentage of Participants with Clostridioides difficile-associated Diarrhea
Measured: During the intervention and immediately after the intervention until death or hospital discharge
Type One Hypersensitivity Reactions
Percentage of Participants with Type One (immediate-type) hypersensitivity reactions
Measured: Three days
Participants With Gallbladder Disease
Percentage of Participants with Gallbladder disease
Measured: During the intervention and immediately after the intervention until death or hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2021
- Study start20 Aug 2021
- Primary completion1 Mar 2024
- Study completion1 Nov 2024
Why it stopped: Lapse in funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Out-Of-Hospital Cardiac ArrestStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- David J. Gagnon
- Sponsor type
- University, hospital or other
- Collaborators
- MaineHealth, National Institute of General Medical Sciences (NIGMS), University of New England
- Responsible party
- Sponsor-investigator, David J. Gagnon, MaineHealth
- Investigators
- David Gagnon, PharmD, Principal investigator, MaineHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04999592
- Sponsor's protocol ID
- 1P20GM139745-01
- Other IDs
- P20GM139745
- Acronym
- PROTECT
- Status last verified
- Apr 2025
- First submitted
- 8 Jul 2021
- Last updated
- 17 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35246202Gagnon DJ, Burkholder KM, Weissman AJ, Riker RR, Ryzhov S, May TL, DiPalazzo J, deKay JT, Knudsen L, Moore MW, Pozzessere NA, Weatherbee M, Kelly M, Nigatu AS, Sevigny JL, Simpson S, Thomas WK, Callaway CW, Geller BJ, Sawyer DB, Seder DB. Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT). Chest. 2026 Jan;169(1):115-127. doi: 10.1016/j.chest.2025.08.007. Epub 2025 Aug 28.
PubMed 40885534
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ceftriaxone to PRevent pneumOnia and inflammatTion aftEr Cardiac arresT (PROTECT): a Randomized-controlled Trial and Microbiome Assessment
- ClinicalTrials.gov ID
- NCT04999592
- Acronym / sponsor ID
- PROTECT / 1P20GM139745-01
- Conditions
- Out-Of-Hospital Cardiac Arrest, Pneumonia
- Keywords
- out-of-hospital cardiac arrest, cardiac arrest, pneumonia, randomized clinical trial, infection, ceftriaxone, microbiome, inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lapse in funding
- Enrolment
- 53 participants (actual)
- Lead sponsor
- David J. GagnonUniversity, hospital or other
- Collaborators
- MaineHealth, National Institute of General Medical Sciences (NIGMS), University of New England
- Study start
- 20 Aug 2021 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Nov 2024 (actual)
- First posted
- 11 Aug 2021 (actual)
- Results
- Posted 17 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No prophylaxis (placebo) | Active comparator | Drug: Standard of care without prophylaxisStandard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection. |
| Prophylaxis | Experimental | Drug: Antibiotic prophylaxisAntibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ≥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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of care without prophylaxisAlso: PlaceboAdminister antibiotics in response to infection | Drug | No prophylaxis (placebo) |
| Antibiotic prophylaxisAlso: Rocephin (ceftriaxone)Ceftriaxone 2 gm IV q12h for 3 days | Drug | Prophylaxis |
Primary outcome
Clinically-diagnosed Early-onset Pneumonia
Time frame: 4 days
Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation
11 secondary outcomes
Microbiologically-confirmed Early-onset Pneumonia
Time frame: 4 days
Microbiologically-confirmed Late-onset Pneumonia
Time frame: ≥ 4 days
Clinically-diagnosed Late-onset Pneumonia
Time frame: ≥ 4 days
Non-pulmonary Infections
Time frame: During the intervention and immediately after the intervention until hospital discharge, up to 6 months
ICU-free Days During Admission
Time frame: 28 days
Mechanical Ventilator-free Days During Admission
Time frame: 28 days
Death in the Hospital
Time frame: During the intervention (3 days) and immediately after the intervention until subject death or hospital discharge, an average of 30 days
Functional Outcome at 6 Months Post-hospital Discharge
Time frame: 6 months post-hospital discharge
Clostridioides Difficile-associated Diarrhea
Time frame: During the intervention and immediately after the intervention until death or hospital discharge
Type One Hypersensitivity Reactions
Time frame: Three days
Participants With Gallbladder Disease
Time frame: During the intervention and immediately after the intervention until death or hospital discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35246202Gagnon 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.
- Derived from this study: PubMed 40885534Gagnon DJ, Burkholder KM, Weissman AJ, Riker RR, Ryzhov S, May TL, DiPalazzo J, deKay JT, Knudsen L, Moore MW, Pozzessere NA, Weatherbee M, Kelly M, Nigatu AS, Sevigny JL, Simpson S, Thomas WK, Callaway CW, Geller BJ, Sawyer DB, Seder DB. Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT). Chest. 2026 Jan;169(1):115-127. doi: 10.1016/j.chest.2025.08.007. Epub 2025 Aug 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Gagnon, PharmD principal investigator
MaineHealth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Antibiotic prophylaxis in people with Out-Of-Hospital Cardiac Arrest and Pneumonia, run by David J. Gagnon at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically-diagnosed Early-onset Pneumonia (time frame: 4 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04999592, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025.