Clinical trial NCT04158804: PROcalcitonin Impact on Antibiotic Reduction, adverSe Events and AVoidable healthcarE Costs (ProSAVE): A RCT
Official title: PROcalcitonin Impact on Antibiotic Reduction, adverSe Events and AVoidable healthcarE Costs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia, Bacterial
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: BRAHMS GmbH
name: Thermo Fisher Scientific, Inc
First posted: 2019-11-12
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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).


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

Primary outcomes:
measure: Short Treatment of Pneumonia
timeFrame: 30 days
Secondary outcomes:
measure: Composite Safety Adverse Event Rate
timeFrame: 30 days
measure: Antibiotic Exposure at Discharge
timeFrame: 30 days
measure: Days of Therapy Per 1000 Patient Days
timeFrame: 30 days
measure: Length of Stay
timeFrame: 30 days
measure: ICU Admissions
timeFrame: 30 days
Other outcomes:
measure: Clostridium Difficile Infection (CDI)
timeFrame: 30 days
measure: Healthcare Economic Endpoints
timeFrame: 30 days
Locations:
city: Torrington
country: United States
facility: Charlotte Hungerford Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Oak Bluffs
country: United States
facility: Martha's Vineyard Hospital
state: Massachusetts
city: Salem
country: United States
facility: North Shore Medical Center
state: Massachusetts
city: Fort Worth
country: United States
facility: Texas Health Harris Methodist Hospital
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Michael K Mansour, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: