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

NCT05568654 | Active Not Recruiting

• 1 other identifier: 21-863
• Study Type: interventional
• Target: 12,500
• Locations: 1 country
• Sites: 12

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of days of broad-spectrum antibiotic therapy

  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 Outcomes (23)

• viral testing ordered (yes/no)

  Up to 48 hours

• detection of influenza virus (yes/no)

  Up to 48 hours

• detection of RSV (yes/no)

  up to 48 hours

• detection of viruses/atypical bacteria in the respiratory panel (yes/no)

  up to 48 hours

• treatment with anti-viral medications

  up to 48 hours

Study Arms (4)

Rapid diagnostic testing (RDT)

ACTIVE COMPARATOR

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.

Diagnostic Test: Rapid Diagnostic Testing

Pharmacist-led de-escalation

ACTIVE COMPARATOR

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

Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation

ACTIVE COMPARATOR

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.

Diagnostic Test: Rapid Diagnostic Testing; Other: Pharmacist-led de-escalation

Usual care (no intervention)

NO INTERVENTION

Usual care

Interventions

Rapid Diagnostic Testing 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.

Rapid diagnostic testing (RDT); Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation

Pharmacist-led de-escalation 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.

Pharmacist-led de-escalation; Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (12)

Indian River Hospital

Vero Beach, Florida, 32960, United States

Location

Weston Hospital/Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Akron General Hospital

Akron, Ohio, 44307, United States

Location

Avon Hospital

Avon, Ohio, 44011, United States

Location

Lutheran Hospital

Cleveland, Ohio, 44113, United States

Location

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

Euclid Hospital

Euclid, Ohio, 44119, United States

Location

Fairview Hospital

Fairview Park, Ohio, 44111, United States

Location

Marymount Hospital

Garfield Heights, Ohio, 44125, United States

Location

Hillcrest Hospital

Mayfield Heights, Ohio, 44124, United States

Location

Medina Hospital

Medina, Ohio, 44256, United States

Location

South Pointe Hospital

Warrensville Heights, Ohio, 44122, United States

Location

Related Publications (12)

• 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.

  PMID: 25337751 BACKGROUND

• 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.

  PMID: 26172429 BACKGROUND

• 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.

  PMID: 31573350 BACKGROUND

• 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.

  PMID: 31587039 BACKGROUND

• 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.

  PMID: 33256870 BACKGROUND

• 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.

  PMID: 32129438 BACKGROUND

• 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.

  PMID: 26538501 BACKGROUND

• 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.

  PMID: 32697323 BACKGROUND

• 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.

  PMID: 31665249 BACKGROUND

• 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.

  PMID: 27048748 BACKGROUND

• 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.

  PMID: 33352192 BACKGROUND

• 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.

  PMID: 37716990 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Michael Rothberg, M.D.

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

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

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 6, 2022
• Study Start: November 1, 2022
• Primary Completion: January 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)