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

Not Applicable

Completed

Conditions: Pneumonia, Bacterial

Interventions: Diagnostic Test: procalcitonin

Registration Number: NCT04158804

Lead Sponsor: Massachusetts General Hospital

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 700

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Procalcitonin algorithm+stewardship team	procalcitonin	antibiotic prescription guided by PCT values

Primary Outcome Measures

Name	Time	Method
Short Treatment of Pneumonia	30 days	Proportion of patients with short treatment of pneumonia with antibiotics (less than 4 days, "shortABx")

Secondary Outcome Measures

Name	Time	Method
Composite Safety Adverse Event Rate	30 days	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
Antibiotic Exposure at Discharge	30 days	Duration of antibiotics prescribed at discharge
Days of Therapy Per 1000 Patient Days	30 days	Days of therapy per 1000 patient days (inclusive of antibiotics prescribed at discharge)
Length of Stay	30 days	Length of stay in hospital
ICU Admissions	30 days	Number of Participants Admitted to the ICU

Trial Locations

Locations (6): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Martha's Vineyard Hospital
🇺🇸
Oak Bluffs, Massachusetts, United States
Grady Memorial Hospital
🇺🇸
Atlanta, Georgia, United States
Texas Health Harris Methodist Hospital
🇺🇸
Fort Worth, Texas, United States
North Shore Medical Center
🇺🇸
Salem, Massachusetts, United States
Charlotte Hungerford Hospital
🇺🇸
Torrington, Connecticut, United States