Clinical trial NCT04381247: Comprehensive Molecular Diagnosis and Management of Hospital- and Ventilator-associated Pneumonia in Norway
Official title: Comprehensive Molecular Diagnosis and Management of Hospital- and Ventilator-associated Pneumonia in Norway
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pneumonia, Ventilator-Associated
Hospital-acquired Pneumonia
Infectious Disease
Infection, Hospital
Antibiotic Resistant Infection
Keywords: pneumonia
hospital-acquired pneumonia
ventilator-associated pneumonia
molecular diagnostics
biomarker
antibiotic stewardship
Lead sponsor: Vestre Viken Hospital Trust
Sponsor class: OTHER
Collaborators: name: Haukeland University Hospital
name: University of Bergen
First posted: 2020-05-08
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients developing pneumonia during hospital stay for other cause.

Brief summary: HVAPNOR consists of Three work packages:

1. Prospective observational study of Hospital (HAP) - and ventilator-Associated pneumonia (VAP) at 5 hospitals in Norway. Establish optimized routines for microbiological sampling, diagnostics and antibiotic stewardship..
2. Biomarker studies in HAP and VAP.
3. Studies on capacity building in HAP and VAP diagnostics.

Detailed description: Lower respiratory tract infections include hospital-acquired pneumonia (HAP) and ventilator- associated pneumonia (VAP) with a very high mortality in critically ill patients. Diagnosis is difficult with an inherent uncertainty and complicated by comorbidity, lack of routines for high-quality airway sampling and low sensitivity of routine microbiological tests. There is limited data on the aetiology and burden from HAP and VAP, and to the investigators knowledge, no previous prospective HAP and VAP studies has been performed in Norway. In the absence of rapid and accurate microbiological diagnosis, seriously ill HAP and VAP patients are often provided broad-spectrum antibiotics that have to be active on putative multi-drug resistant (MDR) bacteria, as failure to initiate prompt adequate therapy is associated with increased mortality. Overuse of broad-spectrum antibiotics promotes the selection and dissemination of MDR bacteria.

HVAPNOR brings together a multidisciplinary research team from Norwegian (Haukeland University Hospital (HUS), University of Bergen (UoB), Vestre Viken Hospital Trust (VVHF), and international institutions (Denmark, Netherlands and United Kingdom), with a strong record in respiratory disease research.

The overall aims of the HVAPNOR study are to improve diagnostic methods, antibiotic stewardship, treatment and management of HAP and VAP. The investigators will in a Norwegian context, map the incidence and the aetiology of HAP/VAP infections. During a two-year period, adult HAP and VAP patients admitted at HUS and VVHF, will be identified and voluntarily included in a prospective descriptive study. The project will strengthen the routines for adequate airway sampling and assess if provision of ultra-rapid, high-quality accurate molecular diagnostics will provide a more comprehensive microbiological etiological diagnose than routine analysis. A direct feedback to the clinician can facilitate pathogen-directed usage of antibiotics. We will evaluate the potential of molecular diagnostic platforms for the detection of pathogens and antimicrobial markers in HAP and VAP. Furthermore, the investigators will identify barriers that inhibit the acceptance of rapid molecular tests; and contribute to the optimisation of treatment protocols for HAP and VAP.

Finally, the study will also evaluate and identify new and clinically relevant diagnostic and prognostic biomarkers, including immune biomarkers and transcriptional profiling, in HAP and VAP.

The HVAPNOR study is in line with the objectives of the funding agencies, addresses clinical research activities to help to ensure that patients receive high-quality and reliable diagnostics and optimized treatment.

Eligibility criteria: A case definition of NV-HAP and VAP will be applied according to the 2005 American Thoracic Society and Infectious Disease Society of America´s clinical practice guidelines (unchanged in the 2016 revision).

Inclusion criteria:

* Age ≥18 years
* Meets case definition criteria (patient admitted to hospital or endotracheal intubation ≥ 48 hours, a new lung infiltrate + ≥2 of the following: temperature \>38˚C, leukocytes \<3.5 or \>11.0, purulent secretions)
* Eligible for lower airways sampling
* Written informed consent

Exclusion criteria:

* Pulmonary embolism, segmental or larger
* Refractory septic shock (meeting the Sepsis-3 definition of septic shock, and requiring vasopressors ≥ 0.5 mcg/kg/min noradrenaline or equivalent dose of other vasopressor(s)
* Glasgow Coma Scale score 3
* Patients not eligible for lower airways sampling
* Palliative situation with life expectancy \< 1 week

Primary outcomes:
measure: Time to microbiological diagnose
timeFrame: September 2020-August 2022
measure: Microbiological diagnose
timeFrame: September 2020-August 2022
measure: Prevalence of resistance mutations
timeFrame: September 2020-August 2022
measure: Change from empirical to targeted antimicrobial treatment
timeFrame: September 2020-August 2022
measure: Time to targeted antimicrobial treatment
timeFrame: September 2020-August 2022
Secondary outcomes:
Other outcomes:
Locations:
city: Drammen
country: Norway
facility: Vestre Viken Health Trust
state: Viken
Study officials:
affiliation: Vestre Viken Hospital Trust
name: Lars Heggelund, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bergen
name: Harleen Grewal, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Bergen
name: Elling Ulvestad, MD, PhD
role: STUDY_DIRECTOR
References: