Comprehensive Molecular Diagnosis and Management of Hospital- and Ventilator-associated Pneumonia in Norway (HVAPNOR)

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.

Study Overview

• Status: Recruiting
• Conditions: Infectious Disease; Hospital-acquired Pneumonia; Pneumonia, Ventilator-Associated; Antibiotic Resistant Infection; Infection, Hospital
• Intervention / Treatment: Diagnostic test: Molecular diagnostics in HAP and VAP

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.

• Study Type: Observational
• Enrollment (Anticipated): 550

Contacts and Locations

• Study Contact: Name: Lars Heggelund, MD, PhD; Phone Number: +47 48285882; Email: lars.heggelund@vestreviken.no
• Study Contact Backup: Name: Harleen Grewal, MD, PhD; Phone Number: +47 99450554; Email: harleen@grewal@uib.no

Study Locations

• Norway
  • Viken
    • Drammen, Viken, Norway, 3004
      • Recruiting
      • Vestre Viken Health Trust
      • Contact: Lars Heggelund, MD; PhD; Phone Number: +47 482 85 882; Email: lars.heggelund@vestreviken.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients developing pneumonia during hospital stay for other cause.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to microbiological diagnose	Hours	September 2020-August 2022
Microbiological diagnose	Microbes	September 2020-August 2022
Prevalence of resistance mutations	Types and numbers	September 2020-August 2022
Change from empirical to targeted antimicrobial treatment	Percentage based upon optimized microbiological diagnostics	September 2020-August 2022
Time to targeted antimicrobial treatment	Hours	September 2020-August 2022

Collaborators and Investigators

• Sponsor: Vestre Viken Hospital Trust
• Collaborators: University of Bergen; Haukeland University Hospital
• Investigators: Principal Investigator: Lars Heggelund, MD, PhD, Vestre Viken Hospital Trust; Study Director: Harleen Grewal, MD, PhD, University of Bergen; Study Director: Elling Ulvestad, MD, PhD, University of Bergen

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: biomarker; antibiotic stewardship; pneumonia; ventilator-associated pneumonia; molecular diagnostics; hospital-acquired pneumonia
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Iatrogenic Disease; Infections; Communicable Diseases; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Cross Infection
• Other Study ID Numbers: VV HVAPNOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol, SAP and ICF will be made avialbe after the study has been initiated. CSR will be made avialbel after publication.
• IPD Sharing Time Frame: September 2020-December 2024.
• IPD Sharing Access Criteria: PI must be contacted
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No