Early Antibiotics After Aspiration in ICU Patients

NCT05079620 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 22-004-02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the use of early antibiotics in ICU patients who appear to have aspirated, to help determine whether this improves outcomes by reducing the later incidence of pneumonia and other negative consequences.

Conditions

Aspiration; Aspiration Pneumonia

Keywords

ventilator associated pneumonia

Outcome Measures

Primary Outcomes (1)

• ICU-free Days

  Number of days not spent in the ICU, between date of admission and 30 days afterwards. Death or discharge can both reduce this measure.

  From admission to 30 days, death, or hospital discharge, whichever occurs first

Secondary Outcomes (16)

• Ventilator-free Days

  From admission to 30 days, death, or hospital discharge, whichever occurs first

• Hospital-free Days

  From admission to 30 days, death, or hospital discharge, whichever occurs first

• Antibiotic-free Days

  Days with no antibiotics from admission to 30 days, death, or hospital discharge, whichever occurs first

• Number of Participants Intubated After Enrollment

  Between admission to 30 days, death, or hospital discharge, whichever occurs first

• Number of Participants Who Underwent Tracheostomy After Enrollment

  Between admission to 30 days, death, or hospital discharge, whichever occurs first

Study Arms (2)

Antibiotics

EXPERIMENTAL

5 days of empiric antibiotics selected from a guideline-appropriate regimen. Alternate agents may be selected by the treating team if allergies or other patient factors mandate, but are still recommended for a 5 day course. Supportive care including oxygen and ventilation can be offered ad libitum. Options include ceftriaxone, Augmentin, cefepime, vancomycin, levofloxacin.

Drug: Ceftriaxone; Drug: Amoxicillin clavulanic acid; Drug: Cefepime; Drug: Vancomycin; Drug: Levofloxacin

Control

NO INTERVENTION

No initial antibiotic therapy unless clinical picture changes or worsens. Supportive care including oxygen and ventilation can be offered ad libitum.

Interventions

Ceftriaxone DRUG

If there is low risk for P. aeruginosa and/or methicillin-resistant staphylococcus aureus (MRSA), as deemed by the treating team: Ceftriaxone 2 g IV, every 24 hours for 5 days

Antibiotics

Amoxicillin clavulanic acid DRUG

At any point after 24 hours, clinicians may (but are not required to) transition stable patients on ceftriaxone to the oral agent Amoxicillin + clavulanate (Augmentin) 875 mg PO or per feeding tube, twice daily for the remainder of 5 days

Also known as: Augmentin

Antibiotics

Cefepime DRUG

If there is significant risk of P. aeruginosa and/or MRSA as deemed by the treating team: Cefepime 2 g IV, every 8 hours for 5 days, plus vancomycin

Antibiotics

Vancomycin DRUG

If there is significant risk of P. aeruginosa and/or MRSA as deemed by the treating team: Vancomycin IV, dosed by trough or AUC/MIC (area under the curve/minimum inhibitory concentration) monitoring for 5 days, plus cefepime. Order nasal MRSA swab and consider discontinuing vancomycin if MRSA swab is negative.

Antibiotics

Levofloxacin DRUG

At any point after 24 hours, clinicians may (but are not required to) transition stable patients on cefepime to levofloxacin PO or per feeding tube, 750 mg every 24 hours for the remainder of 5 days

Antibiotics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admitted to the ICU within the last 24 hours, or with a witnessed aspiration event in the last 24 hours while in the ICU
• Radiographic findings on chest x-ray or CT deemed by the treating ICU team to be consistent with aspiration (e.g. dependent infiltrates or intraluminal airway debris)
• Clinical history consistent with possible aspiration (e.g. cardiac arrest, found unconscious, or with a witnessed aspiration event).

You may not qualify if:

• Already received 3 or more doses of any antibiotic since hospital presentation, unless the last dose was greater than 1 week before enrollment
• Requires antibiotic therapy for the treatment of other infections
• Patient "comfort measures only" at time of screening
• Currently participating in other trials using investigational drugs or interventions
• Currently pregnant
• Currently a prisoner
• The consenting party (patient or their legally authorized representative) is unable to understand or read English at a fifth-grade level.
• or more of the following are present at the time of screening:
• White blood cell count: ≥ 11.0
• Temperature ≥ 38.0C (100.4F)
• Purulent secretions
• S/F (pulse oximetry saturation to FiO2) ratio ≤ 215

Sponsors & Collaborators

• UConn Health: lead

Study Sites (1)

UConn Health, John Dempsey Hospital

Farmington, Connecticut, 06030, United States

Location

Related Publications (12)

• Dragan V, Wei Y, Elligsen M, Kiss A, Walker SAN, Leis JA. Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis. Clin Infect Dis. 2018 Aug 1;67(4):513-518. doi: 10.1093/cid/ciy120.

  PMID: 29438467 BACKGROUND

• Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N. Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Intensive Care Med. 2005 Apr;31(4):510-6. doi: 10.1007/s00134-005-2585-5. Epub 2005 Mar 8.

  PMID: 15754197 BACKGROUND

• DiBardino DM, Wunderink RG. Aspiration pneumonia: a review of modern trends. J Crit Care. 2015 Feb;30(1):40-8. doi: 10.1016/j.jcrc.2014.07.011. Epub 2014 Jul 22.

  PMID: 25129577 BACKGROUND

• El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, Gifford N. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003 Jun 15;167(12):1650-4. doi: 10.1164/rccm.200212-1543OC. Epub 2003 Apr 10.

  PMID: 12689848 BACKGROUND

• Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.

  PMID: 31693806 BACKGROUND

• Lascarrou JB, Lissonde F, Le Thuaut A, Bachoumas K, Colin G, Henry Lagarrigue M, Vinatier I, Fiancette M, Lacherade JC, Yehia A, Joret A, Lebert C, Bourdon S, Martin Lefevre L, Reignier J. Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis. Crit Care Med. 2017 Aug;45(8):1268-1275. doi: 10.1097/CCM.0000000000002525.

  PMID: 28594680 BACKGROUND

• Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST.

  PMID: 31573350 BACKGROUND

• Marik PE. Aspiration syndromes: aspiration pneumonia and pneumonitis. Hosp Pract (1995). 2010 Feb;38(1):35-42. doi: 10.3810/hp.2010.02.276.

  PMID: 20469622 BACKGROUND

• Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999 Jan;115(1):178-83. doi: 10.1378/chest.115.1.178.

  PMID: 9925081 BACKGROUND

• Rebuck JA, Rasmussen JR, Olsen KM. Clinical aspiration-related practice patterns in the intensive care unit: a physician survey. Crit Care Med. 2001 Dec;29(12):2239-44. doi: 10.1097/00003246-200112000-00001.

  PMID: 11801813 BACKGROUND

• Sirvent JM, Torres A, El-Ebiary M, Castro P, de Batlle J, Bonet A. Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma. Am J Respir Crit Care Med. 1997 May;155(5):1729-34. doi: 10.1164/ajrccm.155.5.9154884.

  PMID: 9154884 BACKGROUND

• Valles J, Peredo R, Burgueno MJ, Rodrigues de Freitas AP, Millan S, Espasa M, Martin-Loeches I, Ferrer R, Suarez D, Artigas A. Efficacy of single-dose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013 May;143(5):1219-1225. doi: 10.1378/chest.12-1361.

  PMID: 23715136 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Aspiration; Pneumonia, Ventilator-Associated

Interventions

Ceftriaxone; Amoxicillin-Potassium Clavulanate Combination; Cefepime; Vancomycin; Levofloxacin

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Healthcare-Associated Pneumonia; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

• Title: Brandon Oto
• Organization: UConn Health

oto.brandon@gmail.com

18606792000

Study Officials

• Brandon Oto

  UConn Health, Adult Critical Care

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of Pulmonary, Critical Care and Sleep Medicine

Study Record Dates

• First Submitted: October 2, 2021
• First Posted: October 15, 2021
• Study Start: November 30, 2021
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: December 30, 2025
• Results First Posted: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)