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

Sponsor

The Cleveland Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT05568654

Collaborator

(none)

12,500

Enrollment

Locations

Arms

43.9

Anticipated Duration (Months)

1136.4

Patients Per Site

25.9

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Community-Acquired Pneumonia Antimicrobial Stewardship Point-of-Care Testing	Diagnostic Test: Rapid Diagnostic Testing Other: Pharmacist-led de-escalation	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

12500 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

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:To accomplish these two aims, we will perform a, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms:

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Jan 31, 2026

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of days of broad-spectrum antibiotic therapy [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

Secondary Outcome Measures

viral testing ordered (yes/no) [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)
detection of influenza virus (yes/no) [Up to 48 hours]
Proportion of patients who test positive for influenza
detection of RSV (yes/no) [up to 48 hours]
Proportion of patients who test positive for RSV
detection of viruses/atypical bacteria in the respiratory panel (yes/no) [up to 48 hours]
Proportion of patients who test positive for each of the viruses/atypical bacteria in the respiratory panel
treatment with anti-viral medications [up to 48 hours]
treatment with anti-viral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
treatment with antiviral medications [within 21 days]
treatment with antiviral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
S. pneumoniae urinary antigen test (UAT) performed [up to 48 hours]
Proportion of patients in whom UAT is performed
positive pneumococcal UAT [up to 48 hours]
Proportion of patients with positive pneumococcal UAT
de-escalation by 72 hours from admission (yes/no) [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
re-escalation to broad-spectrum antibiotics after de-escalation (yes/no) [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).
total duration of any antibacterial antibiotic [up to 21 days]
Total duration of any antibacterial antibiotic treatment up to 21 days, including re-initiation of antibiotics
14-day mortality [up to 14 days]
proportion of patients who die by 14 days
30-day mortality [up to 30 days]
proportion of patients who die by 30 days
ICU transfer after admission (> 24 hours after admission) [up to 21 days]
proportion of patients transferred to the ICU >24 hours after admission up to 21 days
healthcare-associated C.difficile Infection (CDI) (yes/no) [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
acute kidney injury after 48 hours (yes/no) after 48 hours [up to 21 days]
Proportion of patients with AKI after 48 hours of admission, up to 21 days
total inpatient cost (from hospital's cost accounting system) [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
hospital length-of-stay (days, hours) [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
empyema (yes/no) [from 48 hours to 21 days]
empyema (pus in the pleural space)
30-day readmission (yes/no) [up to 30 days after discharge]
30-day hospital readmission
Infection with a resistant organism in the future (yes/no) [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria for patient's records:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weston Hospital/Cleveland Clinic Florida	Weston	Florida	United States	33331
2	Akron General Hospital	Akron	Ohio	United States	44307
3	Avon Hospital	Avon	Ohio	United States	44011
4	Lutheran Hospital	Cleveland	Ohio	United States	44113
5	Cleveland Clinic Main Campus	Cleveland	Ohio	United States	44195
6	Euclid Hospital	Euclid	Ohio	United States	44119
7	Fairview Hospital	Fairview Park	Ohio	United States	44111
8	Marymount Hospital	Garfield Heights	Ohio	United States	44125
9	Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
10	Medina Hospital	Medina	Ohio	United States	44256
11	South Pointe Hospital	Warrensville Heights	Ohio	United States	44122

Sponsors and Collaborators

The Cleveland Clinic

Investigators

Principal Investigator: Michael Rothberg, M.D., The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Michael Rothberg, Staff Physician, The Cleveland Clinic

ClinicalTrials.gov Identifier:

NCT05568654

Other Study ID Numbers:

21-863

First Posted:

Oct 6, 2022

Last Update Posted:

Jan 6, 2023

Last Verified:

Jan 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pneumonia

Study Results

No Results Posted as of Jan 6, 2023