PROcalcitonin Impact on Antibiotic Reduction, adverSe Events and AVoidable healthcarE Costs (ProSAVE): A RCT

Study Overview
=================
Brief Summary
-----------------
Trials comparing PCT-guided antibiotic algorithms to standard management show a significant reduction in antibiotic exposure without an increase in mortality or treatment failure. Despite this strong evidence from multiple studies a recent prospective multicentric interventional trial in the US fell short of demonstrating antibiotic reductions by PCT-guided antibiotic management. Amongst other limitations the authors of that study concluded that successful implementation of PCT may require closer educational oversight. As such, this study will compare effectiveness and safety of antibiotic prescription guided by a PCT-algorithm via a Stewardship Team over standard guidelines in hospitalized adult patients with suspected or confirmed LRTI (including sepsis with respiratory focus).

Official Title
-----------------
PROcalcitonin Impact on Antibiotic Reduction, adverSe Events and AVoidable healthcarE Costs

Conditions
-----------------
Pneumonia, Bacterial

Intervention / Treatment
-----------------
* Diagnostic Test: procalcitonin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hospitalized adult patients ≥ 18 years of age Suspected or confirmed pneumonia <28 days at time of admission to the hospital (ED) who are prescribed antibiotics Minimum of 2 (two) blood samples available for PCT value assessment within 24 hours of hospitalization Exclusion Criteria: Patient has tested positive for SARS-CoV-2 Non-hospitalized patients Patients admitted to home health Major surgeries, defined as any procedure in which an incision is made with the exception of superficial procedures (eyes, cornea, skin, dental procedures), organs removed, or normal anatomy altered (e.g. open thoracic, abdominal and/or major orthopedic surgery), in the past 1 month or expected surgical procedure or patient receiving antibiotics for surgical prophylaxis Active metastatic cancer or neuroendocrine tumor or liquid tumor and/or on check point inhibitors within 3 months or has signs of mucositis (e.g. mouth lesions or intestinal bleeding) Known pregnancy Primary and acquired cell-mediated immune deficiency (HIV with CD4 <350 cells/mm³; receipt of systemic chemotherapy and/or biologics in the past 3 months for reasons other than malignancy) Infection where long course antibiotics are the standard of care(>2 weeks) other than anti-inflammatory reasons. Neutropenia (<1,500 ANC) Concomitant non-pulmonary bacterial infection that requires antibiotic therapy based on an active medical team decision Antibiotics given for non-infectious indications (e.g. rifaximin for hepatic encephalopathy) Patients with cystic fibrosis Patients receiving dialysis Patients with solid organ transplant, bone marrow transplant or stem cell transplant recipient ST elevation myocardial infarction Prior enrollment into this study within 30 days Patient experiencing major trauma defined as any injury that could cause prolonged disability and/or an Injury Severity Score >15, and/or burns or patient under extracorporeal circulation confirmed by a second research staff member. Patient with acute viral hepatitis and/or decompensated severe liver cirrhosis (Child-Pugh Class C). Patient with prolonged or severe cardiogenic shock, defined as decreased cardiac output leading to end organ injury (e.g. severe hypotension or AKI or oliguria or altered mental status or cool extremities or respiratory distress AND evidence of metabolic acidosis on lab testing) Patient with pancreatitis, chemical pneumonitis or heat stroke Active infection with invasive fungal pathogen (e.g. candidiasis, aspergillosis) or plasmodium falciparum malaria or mycobacteria Patient under treatment with OKT3 antibodies, OK-432, interleukins, TNF-alpha and other drugs stimulating the release of pro-inflammatory cytokines or resulting in anaphylaxis. Patient is under hospice care Patient with ventilator associated pneumonia Patients with untreated, active, and symptomatic autoimmune disease Patients with empyema, abscess, or cavitary/necrotizing pneumonia Patients actively enrolled in other clinical trial involving immunomodulatory therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Procalcitonin algorithm+stewardship team<br>antibiotic prescription guided by PCT values | Diagnostic Test: procalcitonin<br>* accuracy of procalcitonin as a diagnostic marker in guiding antibiotic therapy in patients with a lower respiratory tract infection<br>|
| No Intervention: standard group<br>standard of care guided by current guidelines | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary objective | difference in safety outcomes, antibiotic exposure and healthcare cost between standard of care group and PCT group | 30 days | 
| Short treatment of pneumonia | Proportion of patients with short treatment of pneumonia with antibiotics (less than 4 days, shortABx) | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite safety adverse event rate | Composite endpoints include: all-cause in-hospital mortality, all-cause mortality after discharge (as available), hospital readmission, septic shock (vasopressor use for > 1 hour), mechanical ventilation (via endotracheal tube), required dialysis, lung abscess/empyema/cavitation/necrotizing pneumonia | 30 days | 
| Antibiotic exposure at discharge | Duration of antibiotics prescribed at discharge | 30 days | 
| Days of therapy per 1000 patient days | Days of therapy per 1000 patient days (inclusive of antibiotics prescribed at discharge) | 30 days | 
| Length of stay | Length of stay in hospital and length of stay in ICU | 30 days | 
| ICU admissions | Number of ICU admissions | 30 days |