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

NeuroTherapia, Inc.

Status: Enrolling

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05568654

21-863

Details and patient eligibility

About

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

Full 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.

Enrollment: 12,500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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12,500 participants in 4 patient groups

Rapid diagnostic testing (RDT)

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Rapid Diagnostic Testing

Pharmacist-led de-escalation

Active Comparator group

Description:

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.

Treatment:

Other: Pharmacist-led de-escalation

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

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Rapid Diagnostic Testing

Other: Pharmacist-led de-escalation

Usual care (no intervention)

No Intervention group

Description:

Usual care