Effect of IN Hospital PCR Based Assessment of Patients With Lower Respiratory Tract Infections on LEngth of Stay (INHALE)

Effect of IN Hospital PCR Based Assessment of Patients With Lower Respiratory Tract Infections on LEngth of Stay - INHALE Trial

Does the use of the BIOFIRE® FILMARRAY® Pneumonia Panel plus in hospitalized patients with lower respiratory infections lead to a reduction in length of hospital stay (LOS) and customized antibiotic treatment (higher amount of specific vs empiric treatment, shorter treatment duration, less antibiotic treatment, lower incidence of side effects) compared to the standard of care?

Study Overview

• Status: Recruiting
• Conditions: Respiratory Infection
• Intervention / Treatment: Diagnostic test: Respiratory Panel PCR Sputum

Detailed Description

Lower respiratory tract infections (LRTIs) like pneumonia, exacerbations of COPD or bronchitis are caused by several viral and/or bacterial pathogens. Even in huge epidemiological studies the causative pathogen can just be detected in approximately 50% of pneumonia cases. In clinical practice the pathogen is only known in few cases, e.g. Legionella via urine antigen test. It is impossible to distinguish the triggering bacteria by clinical parameters and even accurate differentiation between bacterial and viral infections is often not possible. The same problem exists for other LRTIs.

The lack of knowledge of the causative pathogen leads to several problems:

First, clinicians tend to observe patients after treatment initiation for a longer period than probably necessary, which may lead to an increased length of hospital stay. Secondly, the antibiotic treatment has to be broad enough to cover all possible pathogens empirically. This might lead to an overuse of broad-spectrum antibiotics, an increased risk of side effects, the development of antibiotic resistance or even delayed treatment of the causative agent. Finally, antibiotics are prescribed erroneously for viral infections, which have been misinterpreted as bacterial infections by clinicians.

The BIOFIRE® FILMARRAY® Pneumonia Panel plus can help to solve these problems by identifying the causative pathogen in LRTIs within 1.5 hours. The decision of the treatment and its duration would be pathogen driven and no longer just empirically based on a lot of unknown factors.

The investigators would like to perform the following study with two groups: standard of care (control group) vs Pneumonia panel plus (intervention group). Both groups will receive the standard of care treatment but the intervention group will additionally have their sputum analyzed via the BIOFIRE® FILMARRAY® Pneumonia Panel plus.

Additional information empiric vs specific treatment:

• empiric therapy - every antimicrobial therapy prescribed without knowing the pathogen

  o Amoxicillin/Clavulanic acid or Cefuroxime or Ceftriaxone/Cefotaxime or Piperacillin/Tazobactam or Levofloxacin

• Specific therapy - pathogen driven, prescribed knowing the pathogen; narrowed spectrum of agent

  • Pneumococcus - Penicillin G
  • H. influenzae - Cefuroxime or Doxycycline
  • Moraxella - Cefuroxime or Doxycycline
  • MSSA - Cefazolin or Flucloxacillin
  • MRSA - Linezolid or Vancomycin
  • Pseudomonas - Ceftazidime
  • E. coli - Cefuroxime or third generation Cephalosporin or Ciprofloxacin
  • Klebsiella - Cefuroxime or third generation Cephalosporin or Ciprofloxacin
  • Proteus, Serratia - third generation Cephalosporin or Ciprofloxacin
  • Enterobacter cloacae - Ertapenem
  • Legionella - Levofloxacin or Azithromycin
  • Mycoplasma - Azithromycin or Doxycycline
  • In case of ESBLs - Ertapenem or Meropenem
  • In case of carbapenemases - Ceftazidime/Avibactam (OXA48, KPC) or Meropenem/Vaborbactam (KPC) or Aztreonam +/- Ceftazidime/Avibactam (MBL +- others)

• Study Type: Interventional
• Enrollment (Estimated): 302
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander Zoufaly, Prof. Dr.; Phone Number: +43 1 60191 72415; Email: alexander.zoufaly@gesundheitsverbund.at
• Study Contact Backup: Name: Klaus Breinbauer, Dr. med.; Phone Number: +43 1 60191 72454; Email: klaus.breinbauer@gesundheitsverbund.at

Study Locations

• Austria
  • Österreich
    • Wien, Österreich, Austria, 1100
      • Recruiting
      • Klinik Favoriten
      • Contact: Klaus Breinbauer, Dr. med.; Phone Number: +4316019172454; Email: klaus.breinbauer@gesundheitsverbund.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Hospitalised patients on a general ward
• Ability to give consent
• Ability to produce sputum

AND (one of the following diagnosis)

• acute exacerabation of COPD (defined as known COPD and worsening of symptoms like dyspnea +/- wheezing +/- increased sputum purulence and the need for additional treatment)
• Pneumonia (diagnosed via chest X-ray)

OR

Lower respiratory infection (which does not belong to one of the two former diagnosis) with following symptoms:

At least one criterion Cough (more than usual if smoker) Dyspnea Increased sputum purulence

AND (at least one criterion) Respiratory rate ≥22/min Reduced oxygen saturation (<95%) (or worsening of oxygen saturation by 3% (e.g. in patients with COPD) Fever (temp >38°C) Rales/wheezing Chest pain upon breathing

Exclusion Criteria:

• Other proven or suspected systemic diseases which require antibiotic treatment, like:

  • Intraabdominal infections (appendicitis, cholecystitis, diverticulitis, peritonitis)
  • C. difficile associated diarrhea (only if existing on admission otherwise it will be identified as a side effect)
  • Urinary tract infections like pyelonephritis, urosepsis, cystitis + fever (asymptomatic bacteriuria is NOT an exclusion criterion)
  • Acute bacterial skin and skin structure infections (erysipelas, abscess with systemic symptoms, diabetic foot infection, osteomyelitis)
  • Another single cause which can explain the respiratory symptoms better than an infection (acute heart failure, pulmonary embolism, hypertension induced lung edema)
• Proven respiratory infection via another PCR based system (e.g. influenza or tuberculosis)
• Inability to give consent
• Inability to produce sputum
• Moribund and palliative patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; standard of care (SOC) group = control group: Routine laboratory parameters (CBC, CRP, kidney and liver parameters, etc.) on the day of admission and when clinically necessary - decision is made by the physician in charge; Sputum microscopy for quality assessment (via Bartlett score); Chest X-ray on the day of admission or the day after; 2 Sets of blood cultures (if temperature >38°); Pneumococcus urine antigen test for every patient with proven or suspected pneumonia; Legionella urine antigen test for every patient with proven or suspected pneumonia and clinical suspicion for Legionella infection (travel history, air condition, elevated CK, hyponatremia, reduced kidney function); Antibiotic treatment if deemed necessary by the treating physician
Experimental: Standard of Care + Respiratory Panel; Pneumonia panel plus group = intervention group; Sputum analysis via the BIOFIRE® FILMARRAY® Pneumonia Panel plus; Routine laboratory parameters (CBC, CRP, kidney and liver parameters, etc.) on the day of admission and when clinically necessary - decision is made by the physician in charge; Sputum microscopy for quality assessment (via Bartlett score); Chest X-ray on the day of admission or the day after; 2 Sets of blood cultures; Pneumococcus urine antigen test for every patient with proven or suspected pneumonia; Legionella urine antigen test for every patient with proven or suspected pneumonia and; Antibiotic treatment if deemed necessary by the treating physician	Diagnostic test: Respiratory Panel PCR Sputum; Multiplex PCR Respiratory Panel from Biomerieux used on Patients Sputum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
length of stay (LOS) in days	How long is the lenght of stay in days (half-days)?	From admission to discharge or death, whichever comes first, assessed up to 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of antibiotic treatment needed represented as days of treatment (DOT)	How long is the duration of antibiotic treatment in days?	From start of antibiotic treatment to discontinuation of any cause, assessed up to 12 Months
Number of usage of specific vs empiric antibiotic treatment	Is there a difference in used antibiotic treatment?	From start of antibiotic treatment to discontinuation of any cause, assessed up to 12 Months
Cost of antibiotic treatment	Is there a differnece in cost of antibiotic treatment?	From start of antibiotic treatment to discontinuation of any cause, assessed up to 12 Months
In hospital and 30-day mortality	Is there a difference in 30-day mortality?	From admission to death or 30 days after admission
C. difficile associated diarrhea within 30-day-follow-up	Is there a diference in incidence of C. difficile associated diarrhea?	From admission to death or 30 days after admission
30-day re-admission rate	Is there a difference in 30-day re-admission rate?	From admission to death or 30 days after admission

Collaborators and Investigators

• Sponsor: Alexander Zoufaly
• Collaborators: BioMérieux
• Investigators: Principal Investigator: Alexander Zoufaly, Prof. Dr., Klinik Favoriten

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Biofire
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: INHALE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No