Community-Acquired PneumoniaNCT05568654
Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia
A study testing Rapid Diagnostic Testing and Pharmacist-led de-escalation in people with Community-Acquired Pneumonia and Antimicrobial Stewardship, run by The Cleveland Clinic at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Community-Acquired Pneumonia, Antimicrobial Stewardship, Point-of-Care Testing
- What is being tested?
- Rapid Diagnostic Testing and Pharmacist-led de-escalation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28,580 participants
- Where
- 12 sitesUnited States
- Study dates
- 1 Nov 2022to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Akron General Hospital
Akron, Ohio, 44307
Avon Hospital
Avon, Ohio, 44011
Lutheran Hospital
Cleveland, Ohio, 44113
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
Euclid Hospital
Euclid, Ohio, 44119
Fairview Hospital
Fairview Park, Ohio, 44111
Marymount Hospital
Garfield Heights, Ohio, 44125
Hillcrest Hospital
Mayfield Heights, Ohio, 44124
Medina Hospital
Medina, Ohio, 44256
Indian River Hospital
Vero Beach, Florida, 32960
South Pointe Hospital
Warrensville Heights, Ohio, 44122
Weston Hospital/Cleveland Clinic Florida
Weston, Florida, 33331
About this study
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
Read the 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, 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.
- Being tested
- Rapid Diagnostic Testing, Pharmacist-led de-escalation
- Medical subject headings
- Community-Acquired Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapid Diagnostic TestingDiagnostic 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-escalationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Diagnostic Test: Rapid Diagnostic Testing; Other: Pharmacist-led de-escalation |
| Usual care (no intervention) | No intervention | Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: first 21 days of admission
Secondary outcomes (23)
viral testing ordered (yes/no)
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)
Measured: Up to 48 hours
detection of influenza virus (yes/no)
Proportion of patients who test positive for influenza
Measured: Up to 48 hours
detection of RSV (yes/no)
Proportion of patients who test positive for RSV
Measured: up to 48 hours
detection of viruses/atypical bacteria in the respiratory panel (yes/no)
Proportion of patients who test positive for each of the viruses/atypical bacteria in the respiratory panel
Measured: up to 48 hours
treatment with anti-viral medications
treatment with anti-viral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
Measured: up to 48 hours
treatment with antiviral medications
treatment with antiviral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
Measured: within 21 days
S. pneumoniae urinary antigen test (UAT) performed
Proportion of patients in whom UAT is performed
Measured: up to 48 hours
positive pneumococcal UAT
Proportion of patients with positive pneumococcal UAT
Measured: up to 48 hours
de-escalation by 72 hours from admission (yes/no)
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
Measured: within 72 hours from admission.
re-escalation to broad-spectrum antibiotics after de-escalation (yes/no)
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).
Measured: by 21 days from admission
total duration of any antibacterial antibiotic
Total duration of any antibacterial antibiotic treatment up to 21 days, including re-initiation of antibiotics
Measured: up to 21 days
14-day mortality
proportion of patients who die by 14 days
Measured: up to 14 days
30-day mortality
proportion of patients who die by 30 days
Measured: up to 30 days
ICU transfer after admission (> 24 hours after admission)
proportion of patients transferred to the ICU >24 hours after admission up to 21 days
Measured: up to 21 days
healthcare-associated C.difficile Infection (CDI) (yes/no)
CDI after 72 hours of admission. Proportion of patients with CDI after 72 hours of admission (healthcare-associated CDI) until discharge
Measured: after 72 hours of admission until discharge
acute kidney injury after 48 hours (yes/no) after 48 hours
Proportion of patients with AKI after 48 hours of admission, up to 21 days
Measured: up to 21 days
total inpatient cost (from hospital's cost accounting system)
total inpatient cost (from hospital's cost accounting system) - from admission to discharge or 21 days, whichever comes first
Measured: from admission to discharge or 21 days, whichever comes first
hospital length-of-stay (days, hours)
length of stay will be calculated in days from the time of admission to the time of discharge
Measured: days from the time of admission to the time of discharge
empyema (yes/no)
empyema (pus in the pleural space)
Measured: from 48 hours to 21 days
30-day readmission (yes/no)
30-day hospital readmission
Measured: up to 30 days after discharge
Infection with a resistant organism in the future (yes/no)
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
Measured: up to 6 months after discharge
Procalcitonin test (PCT) performed
Procalcitonin test (PCT) performed. Proportion of patients in whom PCT testing is performed
Measured: up to 48 hours
Procalcitonin test (PCT) values
Procalcitonin test (PCT) values. Proportion of patients with low vs high PCT values
Measured: up to 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start1 Nov 2022
- Primary completion31 Jan 2026
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Community-Acquired PneumoniaStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 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)
- Enrolment
- 28,580 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Rothberg, The Cleveland Clinic
- Investigators
- Michael Rothberg, M.D., Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05568654
- Sponsor's protocol ID
- 21-863
- Status last verified
- Jun 2026
- First submitted
- 3 Oct 2022
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25337751Jain 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.
PubMed 26172429Metlay 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.
PubMed 31573350Schimmel 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.
PubMed 31587039Klompas 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.
PubMed 33256870Deshpande 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.
PubMed 32129438Madaras-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.
PubMed 26538501Higgins 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.
PubMed 32697323Haessler 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.
PubMed 31665249Belforti 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.
PubMed 27048748Allgaier 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.
PubMed 33352192Deshpande 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.
PubMed 37716990
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia
- ClinicalTrials.gov ID
- NCT05568654
- Acronym / sponsor ID
- 21-863
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28,580 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 31 Jan 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 6 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- To accomplish these two aims, we will perform a, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms:
| Arm | Type | Receives |
|---|---|---|
| Rapid diagnostic testing (RDT) | Active comparator | Diagnostic Test: Rapid Diagnostic TestingRapid 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. |
| Pharmacist-led de-escalation | Active comparator | Other: Pharmacist-led de-escalationPharmacist-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. |
| Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation | Active comparator | Diagnostic Test: Rapid Diagnostic Testing, Other: Pharmacist-led de-escalationRapid 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. |
| Usual care (no intervention) | No intervention | –Usual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rapid Diagnostic TestingEligible 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. | Diagnostic test | Rapid diagnostic testing (RDT), Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation |
| Pharmacist-led de-escalationA 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. | Other | Pharmacist-led de-escalation, Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation |
Primary outcome
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
23 secondary outcomes
viral testing ordered (yes/no)
Time frame: Up to 48 hours
detection of influenza virus (yes/no)
Time frame: Up to 48 hours
detection of RSV (yes/no)
Time frame: up to 48 hours
detection of viruses/atypical bacteria in the respiratory panel (yes/no)
Time frame: up to 48 hours
treatment with anti-viral medications
Time frame: up to 48 hours
treatment with antiviral medications
Time frame: within 21 days
S. pneumoniae urinary antigen test (UAT) performed
Time frame: up to 48 hours
positive pneumococcal UAT
Time frame: up to 48 hours
de-escalation by 72 hours from admission (yes/no)
Time frame: within 72 hours from admission.
re-escalation to broad-spectrum antibiotics after de-escalation (yes/no)
Time frame: by 21 days from admission
total duration of any antibacterial antibiotic
Time frame: up to 21 days
14-day mortality
Time frame: up to 14 days
30-day mortality
Time frame: up to 30 days
ICU transfer after admission (> 24 hours after admission)
Time frame: up to 21 days
healthcare-associated C.difficile Infection (CDI) (yes/no)
Time frame: after 72 hours of admission until discharge
acute kidney injury after 48 hours (yes/no) after 48 hours
Time frame: 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
hospital length-of-stay (days, hours)
Time frame: days from the time of admission to the time of discharge
empyema (yes/no)
Time frame: from 48 hours to 21 days
30-day readmission (yes/no)
Time frame: up to 30 days after discharge
Infection with a resistant organism in the future (yes/no)
Time frame: up to 6 months after discharge
Procalcitonin test (PCT) performed
Time frame: up to 48 hours
Procalcitonin test (PCT) values
Time frame: up to 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Background: PubMed 25337751Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014 Oct 23;371(17):1619-28. doi: 10.1056/NEJMra1312885. No abstract available.
- Background: PubMed 26172429Jain 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.
- Background: PubMed 31573350Metlay 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.
- Background: PubMed 31587039Schimmel 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.
- Background: PubMed 33256870Klompas 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.
- Background: PubMed 32129438Deshpande 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.
- Background: PubMed 26538501Madaras-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.
- Background: PubMed 32697323Higgins 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.
- Background: PubMed 31665249Haessler 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.
- Background: PubMed 27048748Belforti 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.
- Background: PubMed 33352192Allgaier 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.
- Derived from this study: PubMed 37716990Deshpande 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Rothberg, M.D. principal investigator
The Cleveland Clinic
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rapid Diagnostic Testing and Pharmacist-led de-escalation in people with Community-Acquired Pneumonia and Antimicrobial Stewardship, run by The Cleveland Clinic at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of days of broad-spectrum antibiotic therapy (time frame: first 21 days of admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05568654, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.