Clinical trial NCT05568654: Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia
Official title: Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Community-Acquired Pneumonia
Antimicrobial Stewardship
Point-of-Care Testing
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2022-10-06
Enrollment: 12500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: To accomplish these two aims, we will perform a, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms:
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to reduce the exposure of broad-spectrum antimicrobials by optimizing the rapid detection of CAP pathogens and improving rates of de-escalation following negative cultures. To accomplish this, we will perform a 3-year, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms: a) rapid diagnostic testing b) pharmacist-led de-escalation c) rapid diagnostic testing + pharmacist-led de-escalation and d) usual care

Detailed description: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and inpatient antimicrobial use in the United States. However, diagnostic uncertainty at the time of initial treatment and following negative cultures is associated with prolonged exposure to broad-spectrum antimicrobials. We propose a large multicenter cluster randomized controlled trial to test two approaches to reducing the use of broad-spectrum antibiotics in adult patients with CAP a) routine use of rapid diagnostic testing at the time of admission and b) pharmacist -led de-escalation after 48 hours for clinically stable patients with negative cultures.

When a patient is admitted with a diagnosis of pneumonia, it will trigger the admission order set and if the physician is in a hospital randomized to the rapid diagnostic testing arm, a CDSS-based alert will be generated in real time, and the form will append orders for viral and UAT testing. For physicians at a hospital randomized to the control condition, ordering will proceed as usual (standard-of-care). A second CDSS algorithm will identify study patients who have negative culture results (blood and/or sputum) for greater than 48 hours and generate a list for the antimicrobial stewardship pharmacist, who will be a member of the study team. The alerts will be audited by the clinical pharmacist daily on weekdays at a centralized location. In clinically stable patients from hospitals randomized to the de-escalation arm, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call, Epic chat, or page. The primary outcome will be the duration of exposure to broad-spectrum antimicrobial therapy defined by the number of days of antibiotic therapy from initiation to discontinuation. Secondary outcomes will include detection of influenza/RSV, de-escalation and re-escalation to broad-spectrum antibiotics after de-escalation, total antibiotic duration, in-hospital mortality, ICU transfer after admission, healthcare-associated CDI and acute kidney injury after 48 hours.

Eligibility criteria: Inclusion Criteria for patient's records:

1. Men or women greater than or equal to 18 years of age
2. Admitted to a participating (i.e. enrolled and randomized) hospital
3. Admitting diagnosis of pneumonia

Exclusion Criteria:

1. Admission to intensive care unit within 24 hours of hospital admission
2. Comfort care measures only
3. Cystic fibrosis
4. Discharged from an acute care hospital in the past week
5. Patients not eligible for empiric therapy due to a known pathogen (any positive blood or respiratory cultures in the 72 hours prior to admission)

Primary outcomes:
measure: Number of days of broad-spectrum antibiotic therapy
timeFrame: first 21 days of admission
Secondary outcomes:
measure: viral testing ordered (yes/no)
timeFrame: Up to 48 hours
measure: detection of influenza virus (yes/no)
timeFrame: Up to 48 hours
measure: detection of RSV (yes/no)
timeFrame: up to 48 hours
measure: detection of viruses/atypical bacteria in the respiratory panel (yes/no)
timeFrame: up to 48 hours
measure: treatment with anti-viral medications
timeFrame: up to 48 hours
measure: treatment with antiviral medications
timeFrame: within 21 days
measure: S. pneumoniae urinary antigen test (UAT) performed
timeFrame: up to 48 hours
measure: positive pneumococcal UAT
timeFrame: up to 48 hours
measure: de-escalation by 72 hours from admission (yes/no)
timeFrame: within 72 hours from admission.
measure: re-escalation to broad-spectrum antibiotics after de-escalation (yes/no)
timeFrame: by 21 days from admission
measure: total duration of any antibacterial antibiotic
timeFrame: up to 21 days
measure: 14-day mortality
timeFrame: up to 14 days
measure: 30-day mortality
timeFrame: up to 30 days
measure: ICU transfer after admission (> 24 hours after admission)
timeFrame: up to 21 days
measure: healthcare-associated C.difficile Infection (CDI) (yes/no)
timeFrame: after 72 hours of admission until discharge
measure: acute kidney injury after 48 hours (yes/no) after 48 hours
timeFrame: up to 21 days
measure: total inpatient cost (from hospital's cost accounting system)
timeFrame: from admission to discharge or 21 days, whichever comes first
measure: hospital length-of-stay (days, hours)
timeFrame: days from the time of admission to the time of discharge
measure: empyema (yes/no)
timeFrame: from 48 hours to 21 days
measure: 30-day readmission (yes/no)
timeFrame: up to 30 days after discharge
measure: Infection with a resistant organism in the future (yes/no)
timeFrame: up to 6 months after discharge
Other outcomes:
Locations:
city: Vero Beach
country: United States
facility: Indian River Hospital
state: Florida
city: Weston
country: United States
facility: Weston Hospital/Cleveland Clinic Florida
state: Florida
city: Akron
country: United States
facility: Akron General Hospital
state: Ohio
city: Avon
country: United States
facility: Avon Hospital
state: Ohio
city: Cleveland
country: United States
facility: Lutheran Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Euclid
country: United States
facility: Euclid Hospital
state: Ohio
city: Fairview Park
country: United States
facility: Fairview Hospital
state: Ohio
city: Garfield Heights
country: United States
facility: Marymount Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital
state: Ohio
city: Medina
country: United States
facility: Medina Hospital
state: Ohio
city: Warrensville Heights
country: United States
facility: South Pointe Hospital
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Michael Rothberg, M.D.
role: PRINCIPAL_INVESTIGATOR
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citation: Belforti RK, Lagu T, Haessler S, Lindenauer PK, Pekow PS, Priya A, Zilberberg MD, Skiest D, Higgins TL, Stefan MS, Rothberg MB. Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia. Clin Infect Dis. 2016 Jul 1;63(1):1-9. doi: 10.1093/cid/ciw209. Epub 2016 Apr 5.
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