Early Antibiotics After Aspiration in ICU Patients

NCT ID: NCT05079620

Last Updated: 2025-12-30

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2024-04-12

Brief Summary

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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.

Detailed Description

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ICU patients with signs of aspiration on imaging and a clinical history supportive of aspiration, but with no clear signs of infectious pneumonia, will be randomized to receive either 5 days of empiric antibiotics or supportive care only. They will be followed for 30 days with a primary outcome of ICU length-of-stay and various secondary outcomes including mortality, ventilator days, and antibiotic days.

Conditions

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Aspiration Aspiration Pneumonia

Keywords

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ventilator associated pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Antibiotics

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.

Group Type EXPERIMENTAL

Ceftriaxone

Intervention Type 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

Amoxicillin clavulanic acid

Intervention Type 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

Cefepime

Intervention Type 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

Vancomycin

Intervention Type 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.

Levofloxacin

Intervention Type 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

Control

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Ceftriaxone

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

Intervention Type DRUG

Amoxicillin clavulanic acid

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

Intervention Type DRUG

Cefepime

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

Intervention Type DRUG

Vancomycin

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.

Intervention Type DRUG

Levofloxacin

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

Intervention Type DRUG

Other Intervention Names

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Augmentin

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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.
* 2 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UConn Health

OTHER

Sponsor Role lead

Responsible Party

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Mark Metersky

Chief, Division of Pulmonary, Critical Care and Sleep Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Brandon Oto

Role: STUDY_DIRECTOR

UConn Health, Adult Critical Care

Locations

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UConn Health, John Dempsey Hospital

Farmington, Connecticut, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 29438467 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15754197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25129577 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12689848 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31693806 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28594680 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31573350 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 20469622 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9925081 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11801813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9154884 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23715136 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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22-004-02

Identifier Type: -

Identifier Source: org_study_id