Early Antibiotics After Aspiration in ICU Patients

Sponsor

UConn Health (Other)

Overall Status

Recruiting

CT.gov ID

NCT05079620

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aspiration Aspiration Pneumonia	Drug: Ceftriaxone Drug: Amoxicillin clavulanic acid Drug: Cefepime Drug: Vancomycin Drug: Levofloxacin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Antibiotic Prophylaxis in Critically Ill Patients After Suspected Aspiration

Actual Study Start Date :

Nov 30, 2021

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Apr 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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 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 Other Names: Augmentin 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 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. 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
No Intervention: Control No initial antibiotic therapy unless clinical picture changes or worsens. Supportive care including oxygen and ventilation can be offered ad libitum.

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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

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

Other Names:

Augmentin

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

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.

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

No Intervention: Control

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

Outcome Measures

Primary Outcome Measures

ICU-free days [From admission to 30 days, death, or hospital discharge, whichever occurs first]

Secondary Outcome Measures

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]
Intubated after enrollment [Between admission to 30 days, death, or hospital discharge, whichever occurs first]
Yes/no
Tracheostomy after enrollment [Between admission to 30 days, death, or hospital discharge, whichever occurs first]
Yes/no
Developed pneumonia after enrollment [Between admission to 30 days, death, or hospital discharge, whichever occurs first]
Yes/no, by criteria: 2 or more present simultaneously of temperature >38c, WBC >11k, S/F ratio <215, and purulent secretions
Days before developing pneumonia criteria [Between admission to 30 days, death, or hospital discharge, whichever occurs first]
By criteria: 2 or more present simultaneously of temperature >38c, WBC >11k, S/F ratio <215, and purulent secretions
Additional antibiotics prescribed [Between admission to 30 days, death, or hospital discharge, whichever occurs first]
Yes/no. Excluding prophylactic antibiotics and excluding perioperative prophylactic antibiotics.
Positive sputum culture with presumed pathogen [Between enrollment and 30 days, death, or hospital discharge, whichever occurs first]
Yes/no
Any positive culture with organism resistant to prophylactic antibiotics [Between admission and 30 days, death, or hospital discharge, whichever occurs first]
Yes/no
Positive C. Difficile stool toxin assay after enrollment [Between enrollment and 30 days, death, or hospital discharge, whichever occurs first]
Yes/no
Temperature >38 centigrade on day 3 [Day 3 after enrollment]
Yes/no
White blood cell count >11k on day 3 [Day 3 after enrollment]
Yes/no
Arterial oxygen saturation / Fraction of inspired oxygen (S/F) <215 on day 3 [Day 3 after enrollment]
Yes/no
Purulent secretions [Day 3 after enrollment]
Yes/no

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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