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| ID | Type | Description | Link |
|---|---|---|---|
| P20GM139745 | U.S. NIH Grant/Contract | View source |
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Lapse in funding
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| Name | Class |
|---|---|
| MaineHealth | OTHER |
| National Institute of General Medical Sciences (NIGMS) | NIH |
| University of New England | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| No prophylaxis (placebo) | Active Comparator | Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection. |
|
| Prophylaxis | Experimental | Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard of care without prophylaxis | Drug | Administer antibiotics in response to infection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinically-diagnosed Early-onset Pneumonia | Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation | 4 days |
| Measure | Description | Time Frame |
|---|---|---|
| Microbiologically-confirmed Early-onset Pneumonia | Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation | 4 days |
| Microbiologically-confirmed Late-onset Pneumonia |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| David Gagnon, PharmD | MaineHealth | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maine Medical Center | Portland | Maine | 04102 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35246202 | Background | 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. | |
| 40885534 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | No Prophylaxis (Placebo) | Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection. Standard of care without prophylaxis: Administer antibiotics in response to infection |
| FG001 | Prophylaxis | Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. Antibiotic prophylaxis: Ceftriaxone 2 gm IV q12h for 3 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
53 subjects were consented and 1 withdrew consent leaving 52 subjects (26 in each arm) evaluable.
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| ID | Title | Description |
|---|---|---|
| BG000 | No Prophylaxis (Placebo) | Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection. Standard of care without prophylaxis: Administer antibiotics in response to infection |
| BG001 | Prophylaxis |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinically-diagnosed Early-onset Pneumonia | Percentage of Participants with Clinically-diagnosed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation | Posted | Count of Participants | Participants | 4 days |
|
Enrollment to hospital discharge or death, whichever occurred first, on average 30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | No Prophylaxis (Placebo) | Standard care without antibiotic prophylaxis and treatment of infection if clinically warranted. Administer antibiotics in response to infection. Standard of care without prophylaxis: Administer antibiotics in response to infection |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David J. Gagnon, PharmD - Principal Investigator | MaineHealth Maine Medical Center - Portland | 207-662-0111 | dgagnon@mmc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 19, 2023 | Mar 5, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D058687 | Out-of-Hospital Cardiac Arrest |
| D011014 | Pneumonia |
| D006323 | Heart Arrest |
| D007239 | Infections |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| D019072 | Antibiotic Prophylaxis |
| D002443 | Ceftriaxone |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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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.
| Antibiotic prophylaxis | Drug | Ceftriaxone 2 gm IV q12h for 3 days |
|
|
Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation |
| ≥ 4 days |
| Clinically-diagnosed Late-onset Pneumonia | Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation | ≥ 4 days |
| Non-pulmonary Infections | Percentage of Participants with non-pulmonary infections | 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 | 28 days |
| Mechanical Ventilator-free Days During Admission | Mechanical ventilator-free days in the first 28 days of admission | 28 days |
| Death in the Hospital | Percentage of Participants who Die in the Hospital during admission | 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 | 6 months post-hospital discharge |
| Clostridioides Difficile-associated Diarrhea | Percentage of Participants with Clostridioides difficile-associated Diarrhea | 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 | Three days |
| Participants With Gallbladder Disease | Percentage of Participants with Gallbladder disease | During the intervention and immediately after the intervention until death or hospital discharge |
| Gagnon 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. |
Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. Antibiotic prophylaxis: Ceftriaxone 2 gm IV q12h for 3 days |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Microbiologically-confirmed Early-onset Pneumonia | Percentage of Participants with Microbiologically-confirmed Early-onset Pneumonia occurring <4 days after initiation of mechanical ventilation | Posted | Count of Participants | Participants | 4 days |
|
|
|
| Secondary | Microbiologically-confirmed Late-onset Pneumonia | Percentage of Participants with Microbiologically-confirmed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation | Posted | Count of Participants | Participants | ≥ 4 days |
|
|
|
| Secondary | Clinically-diagnosed Late-onset Pneumonia | Percentage of Participants with Clinically-diagnosed late-onset pneumonia occurring ≥4 days after initiation of mechanical ventilation | Posted | Count of Participants | Participants | ≥ 4 days |
|
|
|
| Secondary | Non-pulmonary Infections | Percentage of Participants with non-pulmonary infections | Posted | Count of Participants | Participants | During the intervention and immediately after the intervention until hospital discharge, up to 6 months |
|
|
|
| Secondary | ICU-free Days During Admission | ICU-free days in the first 28 days of admission | Posted | Median | Inter-Quartile Range | days | 28 days |
|
|
|
| Secondary | Mechanical Ventilator-free Days During Admission | Mechanical ventilator-free days in the first 28 days of admission | Posted | Median | Inter-Quartile Range | days | 28 days |
|
|
|
| Secondary | Death in the Hospital | Percentage of Participants who Die in the Hospital during admission | Posted | Count of Participants | Participants | During the intervention (3 days) and immediately after the intervention until subject death or hospital discharge, an average of 30 days |
|
|
|
| Secondary | 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 | Posted | Median | Inter-Quartile Range | units on a scale | 6 months post-hospital discharge |
|
|
|
| Secondary | Clostridioides Difficile-associated Diarrhea | Percentage of Participants with Clostridioides difficile-associated Diarrhea | Posted | Count of Participants | Participants | During the intervention and immediately after the intervention until death or hospital discharge |
|
|
|
| Secondary | Type One Hypersensitivity Reactions | Percentage of Participants with Type One (immediate-type) hypersensitivity reactions | Posted | Count of Participants | Participants | Three days |
|
|
|
| Secondary | Participants With Gallbladder Disease | Percentage of Participants with Gallbladder disease | Posted | Count of Participants | Participants | During the intervention and immediately after the intervention until death or hospital discharge |
|
|
|
| 19 |
| 26 |
| 0 |
| 26 |
| 0 |
| 26 |
| EG001 | Prophylaxis | Antibiotic prophylaxis for 3 days. Antibiotic prophylaxis with Ceftriaxone 2 gm IV q12h for 3 days. Antibiotic prophylaxis: Ceftriaxone 2 gm IV q12h for 3 days | 11 | 26 | 0 | 26 | 0 | 26 |
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| D012140 |
| Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018890 | Chemoprevention |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D011292 | Premedication |
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |