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

NCT ID: NCT05568654

Last Updated: 2025-07-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

12500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-01

Study Completion Date

2026-06-30

Brief Summary

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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

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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, UAT and procalcitonin 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.

Conditions

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Community-Acquired Pneumonia Antimicrobial Stewardship Point-of-Care Testing

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

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

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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 and procalcitonin 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, UAT and procalcitonin testing to providers in hospitals randomized to receive it.

Group Type ACTIVE_COMPARATOR

Rapid Diagnostic Testing

Intervention Type DIAGNOSTIC_TEST

Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin 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, UAT and procalcitonin testing.

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.

Group Type ACTIVE_COMPARATOR

Pharmacist-led de-escalation

Intervention Type OTHER

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.

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 and procalcitonin 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, UAT and procalcitonin 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.

Group Type ACTIVE_COMPARATOR

Rapid Diagnostic Testing

Intervention Type DIAGNOSTIC_TEST

Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin 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, UAT and procalcitonin testing.

Pharmacist-led de-escalation

Intervention Type OTHER

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.

Usual care (no intervention)

Usual care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Rapid Diagnostic Testing

Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin 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, UAT and procalcitonin testing.

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

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Michael Rothberg

Staff Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Rothberg, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Indian River Hospital

Vero Beach, Florida, United States

Site Status RECRUITING

Weston Hospital/Cleveland Clinic Florida

Weston, Florida, United States

Site Status RECRUITING

Akron General Hospital

Akron, Ohio, United States

Site Status RECRUITING

Avon Hospital

Avon, Ohio, United States

Site Status RECRUITING

Lutheran Hospital

Cleveland, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Main Campus

Cleveland, Ohio, United States

Site Status RECRUITING

Euclid Hospital

Euclid, Ohio, United States

Site Status RECRUITING

Fairview Hospital

Fairview Park, Ohio, United States

Site Status RECRUITING

Marymount Hospital

Garfield Heights, Ohio, United States

Site Status RECRUITING

Hillcrest Hospital

Mayfield Heights, Ohio, United States

Site Status RECRUITING

Medina Hospital

Medina, Ohio, United States

Site Status RECRUITING

South Pointe Hospital

Warrensville Heights, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael Rothberg, M.D.

Role: CONTACT

216-445-0719

Abhishek Deshpande, M.D., PhD

Role: CONTACT

216-445-6207

Facility Contacts

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Kruti Yagnik, DO

Role: primary

772-794-5631

Richard Rothman, MD

Role: primary

772-567-4311 ext. 2000

Donald Dumford, MD

Role: primary

330-344-8971

Rosa Solis, MD

Role: primary

Jay Bhimani, MD

Role: primary

Kanza Qaiser, MD

Role: primary

216-215-7254

Beverly O'Neill, MD

Role: primary

216-692-7848

Ali Acker Gantz, CNP

Role: primary

Debasis Sahoo, MD

Role: primary

Aaron Hamilton, MD

Role: primary

440-312-3000

Shameer Khubber, MD

Role: primary

Ryan Heaney, MD

Role: primary

216-491-6110

References

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Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014 Oct 23;371(17):1619-28. doi: 10.1056/NEJMra1312885. No abstract available.

Reference Type BACKGROUND
PMID: 25337751 (View on PubMed)

Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015 Jul 30;373(5):415-27. doi: 10.1056/NEJMoa1500245. Epub 2015 Jul 14.

Reference Type BACKGROUND
PMID: 26172429 (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)

Schimmel JJ, Haessler S, Imrey P, Lindenauer PK, Richter SS, Yu PC, Rothberg MB. Pneumococcal Urinary Antigen Testing in United States Hospitals: A Missed Opportunity for Antimicrobial Stewardship. Clin Infect Dis. 2020 Sep 12;71(6):1427-1434. doi: 10.1093/cid/ciz983.

Reference Type BACKGROUND
PMID: 31587039 (View on PubMed)

Klompas M, Imrey PB, Yu PC, Rhee C, Deshpande A, Haessler S, Zilberberg MD, Rothberg MB. Respiratory viral testing and antibacterial treatment in patients hospitalized with community-acquired pneumonia. Infect Control Hosp Epidemiol. 2021 Jul;42(7):817-825. doi: 10.1017/ice.2020.1312. Epub 2020 Dec 1.

Reference Type BACKGROUND
PMID: 33256870 (View on PubMed)

Deshpande A, Richter SS, Haessler S, Lindenauer PK, Yu PC, Zilberberg MD, Imrey PB, Higgins T, Rothberg MB. De-escalation of Empiric Antibiotics Following Negative Cultures in Hospitalized Patients With Pneumonia: Rates and Outcomes. Clin Infect Dis. 2021 Apr 26;72(8):1314-1322. doi: 10.1093/cid/ciaa212.

Reference Type BACKGROUND
PMID: 32129438 (View on PubMed)

Madaras-Kelly K, Jones M, Remington R, Caplinger CM, Huttner B, Jones B, Samore M. Antimicrobial de-escalation of treatment for healthcare-associated pneumonia within the Veterans Healthcare Administration. J Antimicrob Chemother. 2016 Feb;71(2):539-46. doi: 10.1093/jac/dkv338. Epub 2015 Nov 3.

Reference Type BACKGROUND
PMID: 26538501 (View on PubMed)

Higgins TL, Deshpande A, Zilberberg MD, Lindenauer PK, Imrey PB, Yu PC, Haessler SD, Richter SS, Rothberg MB. Assessment of the Accuracy of Using ICD-9 Diagnosis Codes to Identify Pneumonia Etiology in Patients Hospitalized With Pneumonia. JAMA Netw Open. 2020 Jul 1;3(7):e207750. doi: 10.1001/jamanetworkopen.2020.7750.

Reference Type BACKGROUND
PMID: 32697323 (View on PubMed)

Haessler S, Lindenauer PK, Zilberberg MD, Imrey PB, Yu PC, Higgins T, Deshpande A, Rothberg MB. Blood Cultures Versus Respiratory Cultures: 2 Different Views of Pneumonia. Clin Infect Dis. 2020 Oct 23;71(7):1604-1612. doi: 10.1093/cid/ciz1049.

Reference Type BACKGROUND
PMID: 31665249 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27048748 (View on PubMed)

Allgaier J, Lagu T, Haessler S, Imrey PB, Deshpande A, Guo N, Rothberg MB. Risk Factors, Management, and Outcomes of Legionella Pneumonia in a Large, Nationally Representative Sample. Chest. 2021 May;159(5):1782-1792. doi: 10.1016/j.chest.2020.12.013. Epub 2020 Dec 19.

Reference Type BACKGROUND
PMID: 33352192 (View on PubMed)

Deshpande A, Walker R, Schulte R, Pallotta AM, Tereshchenko LG, Hu B, Kadri SS, Klompas M, Rothberg MB. Reducing antimicrobial overuse through targeted therapy for patients with community-acquired pneumonia: a study protocol for a cluster-randomized factorial controlled trial (CARE-CAP). Trials. 2023 Sep 16;24(1):595. doi: 10.1186/s13063-023-07615-3.

Reference Type DERIVED
PMID: 37716990 (View on PubMed)

Other Identifiers

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21-863

Identifier Type: -

Identifier Source: org_study_id

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