Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia

March 6, 2023 updated by: Michael Rothberg, The Cleveland Clinic
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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

12500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Abhishek Deshpande, M.D., PhD
  • Phone Number: 216-445-6207
  • Email: DESHPAA2@ccf.org

Study Locations

  • United States
    • Florida
      • Vero Beach, Florida, United States, 32960
        • Recruiting
        • Indian River Hospital
        • Contact:
      • Weston, Florida, United States, 33331
        • Recruiting
        • Weston Hospital/Cleveland Clinic Florida
        • Contact:
          • Richard Rothman, MD
          • Phone Number: 2000 772-567-4311
          • Email: ROTHMAR@ccf.org
    • Ohio
      • Akron, Ohio, United States, 44307
        • Recruiting
        • Akron General Hospital
        • Contact:
      • Avon, Ohio, United States, 44011
        • Recruiting
        • Avon Hospital
        • Contact:
          • Rosa Solis, MD
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Main Campus
        • Contact:
      • Cleveland, Ohio, United States, 44113
      • Euclid, Ohio, United States, 44119
        • Recruiting
        • Euclid Hospital
        • Contact:
      • Fairview Park, Ohio, United States, 44111
        • Recruiting
        • Fairview Hospital
        • Contact:
          • Ali Acker Gantz, CNP
      • Garfield Heights, Ohio, United States, 44125
        • Recruiting
        • Marymount Hospital
        • Contact:
          • Debasis Sahoo, MD
      • Mayfield Heights, Ohio, United States, 44124
        • Recruiting
        • Hillcrest Hospital
        • Contact:
      • Medina, Ohio, United States, 44256
        • Recruiting
        • Medina Hospital
        • Contact:
          • Shameer Khubber, MD
      • Warrensville Heights, Ohio, United States, 44122
        • Recruiting
        • South Pointe Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rapid diagnostic testing (RDT)
Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing and UAT testing to providers in hospitals randomized to receive it.
Diagnostic test: Rapid Diagnostic Testing
Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. A CDSS-based alert will be generated in real time. If the patient is not being admitted to the intensive care unit, the form will append orders for viral pathogen and UAT testing.
Active Comparator: Pharmacist-led de-escalation
Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for > 48 hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. The validated measures of clinical stability in patients with CAP are a) resolved vital sign abnormalities b) normal mental status c) ability to eat. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page.
Other: Pharmacist-led de-escalation
A CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results 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 pharmacist daily at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. The validated measures of clinical stability in patients with CAP are a) resolved vital sign abnormalities (temperature, heart rate, oxygen saturation, blood pressure and respiratory rate) b) normal mental status and c) ability to eat. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page. The de-escalation recommendations made by the pharmacist will be based on a protocol developed by the research team.
Active Comparator: Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation

Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing and UAT testing to providers in hospitals randomized to receive it.

Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for >48-hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page.
Diagnostic test: Rapid Diagnostic Testing
Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. A CDSS-based alert will be generated in real time. If the patient is not being admitted to the intensive care unit, the form will append orders for viral pathogen and UAT testing.
Other: Pharmacist-led de-escalation
A CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results 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 pharmacist daily at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. The validated measures of clinical stability in patients with CAP are a) resolved vital sign abnormalities (temperature, heart rate, oxygen saturation, blood pressure and respiratory rate) b) normal mental status and c) ability to eat. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page. The de-escalation recommendations made by the pharmacist will be based on a protocol developed by the research team.
No Intervention: Usual care (no intervention)
Usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of days of broad-spectrum antibiotic therapy
Time Frame: first 21 days of admission
duration of exposure to broad-spectrum antimicrobial therapy defined by the number of days of antibiotic therapy in the first 21 days of admission as per National Healthcare Safety Network (NHSN) guidelines
first 21 days of admission

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
viral testing ordered (yes/no)
Time Frame: Up to 48 hours
Proportion of patients in whom viral testing was ordered. We will look at each virus individually as well as all viruses together (i.e. any viral testing)
Up to 48 hours
detection of influenza virus (yes/no)
Time Frame: Up to 48 hours
Proportion of patients who test positive for influenza
Up to 48 hours
detection of RSV (yes/no)
Time Frame: up to 48 hours
Proportion of patients who test positive for RSV
up to 48 hours
detection of viruses/atypical bacteria in the respiratory panel (yes/no)
Time Frame: up to 48 hours
Proportion of patients who test positive for each of the viruses/atypical bacteria in the respiratory panel
up to 48 hours
treatment with anti-viral medications
Time Frame: up to 48 hours
treatment with anti-viral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
up to 48 hours
treatment with antiviral medications
Time Frame: within 21 days
treatment with antiviral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
within 21 days
S. pneumoniae urinary antigen test (UAT) performed
Time Frame: up to 48 hours
Proportion of patients in whom UAT is performed
up to 48 hours
positive pneumococcal UAT
Time Frame: up to 48 hours
Proportion of patients with positive pneumococcal UAT
up to 48 hours
de-escalation by 72 hours from admission (yes/no)
Time Frame: within 72 hours from admission.
Proportion of patients whose broad spectrum antimicrobials (imipenem, meropenem, piperacillin-tazobactam, aztreonam, cefepime, ceftazidime, tobramycin, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, ceftaroline, tigecycline, eravacycline, amikacin, linezolid or vancomycin) are de-escalated
within 72 hours from admission.
re-escalation to broad-spectrum antibiotics after de-escalation (yes/no)
Time Frame: by 21 days from admission
Proportion of patients whose antibiotics were de-escalated and that were subsequently re-escalated to broad-spectrum antibiotics (imipenem, meropenem, piperacillin-tazobactam, aztreonam, cefepime, ceftazidime, tobramycin, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, ceftaroline, tigecycline, eravacycline, amikacin, linezolid or vancomycin).
by 21 days from admission
total duration of any antibacterial antibiotic
Time Frame: up to 21 days
Total duration of any antibacterial antibiotic treatment up to 21 days, including re-initiation of antibiotics
up to 21 days
14-day mortality
Time Frame: up to 14 days
proportion of patients who die by 14 days
up to 14 days
30-day mortality
Time Frame: up to 30 days
proportion of patients who die by 30 days
up to 30 days
ICU transfer after admission (> 24 hours after admission)
Time Frame: up to 21 days
proportion of patients transferred to the ICU >24 hours after admission up to 21 days
up to 21 days
healthcare-associated C.difficile Infection (CDI) (yes/no)
Time Frame: after 72 hours of admission until discharge
CDI after 72 hours of admission. Proportion of patients with CDI after 72 hours of admission (healthcare-associated CDI) until discharge
after 72 hours of admission until discharge
acute kidney injury after 48 hours (yes/no) after 48 hours
Time Frame: up to 21 days
Proportion of patients with AKI after 48 hours of admission, up to 21 days
up to 21 days
total inpatient cost (from hospital's cost accounting system)
Time Frame: from admission to discharge or 21 days, whichever comes first
total inpatient cost (from hospital's cost accounting system) - from admission to discharge or 21 days, whichever comes first
from admission to discharge or 21 days, whichever comes first
hospital length-of-stay (days, hours)
Time Frame: days from the time of admission to the time of discharge
length of stay will be calculated in days from the time of admission to the time of discharge
days from the time of admission to the time of discharge
empyema (yes/no)
Time Frame: from 48 hours to 21 days
empyema (pus in the pleural space)
from 48 hours to 21 days
30-day readmission (yes/no)
Time Frame: up to 30 days after discharge
30-day hospital readmission
up to 30 days after discharge
Infection with a resistant organism in the future (yes/no)
Time Frame: up to 6 months after discharge
up to 6 months after discharge. Resistance to CAP therapy will be defined as resistance to either a respiratory quinolone or to both a beta-lactam/3rd generation cephalosporin and a macrolide. Multi-drug resistance will be defined as any CAP bacterial isolate that tests either intermediate (I) or resistant (R) to at least one agent in three or more antimicrobial classes
up to 6 months after discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Anticipated)

January 31, 2026

Study Completion (Anticipated)

June 30, 2026

Study Registration Dates

First Submitted

October 3, 2022

First Submitted That Met QC Criteria

October 3, 2022

First Posted (Actual)

October 6, 2022

Study Record Updates

Last Update Posted (Estimate)

March 7, 2023

Last Update Submitted That Met QC Criteria

March 6, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-863

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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