PROcalcitonin Impact on Antibiotic Reduction, adverSe Events and AVoidable healthcarE Costs (ProSAVE): A RCT
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Procalcitonin algorithm+stewardship team antibiotic prescription guided by PCT values |
Diagnostic Test: procalcitonin
accuracy of procalcitonin as a diagnostic marker in guiding antibiotic therapy in patients with a lower respiratory tract infection
|
| No Intervention: standard group standard of care guided by current guidelines |
Outcome Measures
Primary Outcome Measures
- Primary objective [30 days]
difference in safety outcomes, antibiotic exposure and healthcare cost between standard of care group and PCT group
- Composite safety adverse event rate at 30 days [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
Secondary Outcome Measures
- hospital stay [30 days]
difference in length of hospital stay including ICU duration and resource utilization between standard of care and PCT group
- Antibiotic duration [30 days]
Endpoints include: number of patients with short antibiotic treatments (<4 days of antibiotic treatment), antibiotic exposure at discharge, days of therapy per 1000 patients days (inclusive of antibiotics prescribed at discharge)
Other Outcome Measures
- Clostridium difficile infection (CDI) [30 days]
Treatment or readmission for CDI until day 30 after discharge
- Healthcare economic endpoints [30 days]
Costs associated with primary hospitalization, readmission for CDI, and loss of function
Eligibility Criteria
Criteria
Inclusion Criteria:
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Hospitalized adult patients ≥ 18 years of age
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Suspected or confirmed pneumonia <28 days at time of admission to the hospital (ED) who are prescribed antibiotics
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Minimum of 2 (two) blood samples available for PCT value assessment within 24 hours of hospitalization
Exclusion Criteria:
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Patient has tested positive for SARS-CoV-2
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Non-hospitalized patients
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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
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Active malignancy and/or active chemotherapy within 3 months
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Known pregnancy
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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)
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Infection where long course antibiotics are the standard of care(>2 weeks) other than anti-inflammatory reasons.
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Neutropenia
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Concomitant non-pulmonary bacterial infection that requires antibiotic therapy based on an active medical team decision
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Antibiotics given for non-infectious indications (e.g. rifaximin for hepatic encephalopathy)
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Patients with cystic fibrosis
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Patients receiving dialysis for end-stage renal disease
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Patients with solid organ transplant, bone marrow transplant or stem cell transplant recipient
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ST elevation myocardial infarction
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Prior enrollment into this study within 30 days
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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.
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Patient with acute viral hepatitis and/or decompensated severe liver cirrhosis (Child-Pugh Class C).
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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)
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Patient with pancreatitis, chemical pneumonitis or heat stroke
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Active infection with invasive fungal pathogen (e.g. candidiasis, aspergillosis) or plasmodium falciparum malaria or mycobacteria
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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.
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Patient is under hospice care
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Patient with ventilator associated pneumonia
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Patients with untreated, active, and symptomatic autoimmune disease
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Patients with empyema, abscess, or cavitary/necrotizing pneumonia
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Patients actively enrolled in other clinical trial involving immunomodulatory therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Charlotte Hungerford Hospital | Torrington | Connecticut | United States | 06790 |
| 2 | Grady Memorial Hospital | Atlanta | Georgia | United States | 30303 |
| 3 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 4 | Martha's Vineyard Hospital | Oak Bluffs | Massachusetts | United States | 02557 |
| 5 | North Shore Medical Center | Salem | Massachusetts | United States | 01970 |
Sponsors and Collaborators
- Massachusetts General Hospital
- B·R·A·H·M·S GmbH , part of Thermo Fisher Scientific
Investigators
- Principal Investigator: Michael K Mansour, MD, PhD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019P000362