Impact of Molecular Testing on Improved Diagnosis, Treatment and Management of CAP

NCT04660084 | Terminated DMC

• 1 other identifier: HaukelandUH_31935
• Study Type: interventional
• Target: 374
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will recruit patients suspected of community-acquired pneumonia at Haukeland University Hospital, Bergen, into a pragmatic randomized controlled trial to assess if provision of ultra-rapid, high-quality accurate molecular diagnostics with direct feedback to the clinician can facilitate pathogen-directed usage of antibiotics, shorten antibiotic exposure and admission time and is safe. Additionally, transcriptional and immune marker profiling of patients will guide appropriate management through a targeted focus on the individual patient's physical capacity, nutritional status and co- morbidities. The pragmatic design of this trial together with broad inclusion criteria and a straightforward intervention would make our results generalisable to other similar centres.

Conditions

Pneumonia

Keywords

Microbiology; Bacteria and viruses; Rapid diagnosis; Antibiotic resistance; Diagnostic stewardship

Outcome Measures

Primary Outcomes (2)

• The provision of pathogen-directed treatment based on a microbiological test result deemed as clinically relevant within 48 hours of receipt of respiratory samples.

  Binary outcome: yes: it was provided/no: it was not provided

  "Up to 72 hours"

• Time in hours from receipt of respiratory specimens to receiving pathogen-directed treatment

  Quantitative outcome (measured in hours): time from receipt of respiratory specimens to provision of pathogen-directed treatment based on a microbiological test result deemed as clinically relevant or an elapse of 48 hours, whichever event came first.

  "Up to 72 hours"

Secondary Outcomes (12)

• Duration of antibiotic use in days

  "Up to 4 weeks"

• Proportion of patients receiving narrow-spectrum antibiotics within 48 hours from study inclusion

  "Up to 4 weeks"

• Proportion of patients receiving a single dose of antibiotics

  "Up to 1 week"

• Proportion of patients receiving ≤48 h of antibiotics

  "Up to 1 week"

• Proportion of patients receiving intravenous antibiotics

  "Up to 1 week"

Study Arms (2)

Ultra-rapid molecular point-of-care testing

OTHER

Extended and more rapid diagnostics on microbiological specimens and an active feedback to treating staff with results.

Diagnostic Test: Ultra-rapid molecular point-of-care testing

Standard of care

NO INTERVENTION

Standard collection of microbiological specimens and standard reply to treating staff.

Interventions

Ultra-rapid molecular point-of-care testing DIAGNOSTIC_TEST

Ultra-rapid molecular testing (UR-MT) comprises automated detection using the new BioFire® FilmArray® Pneumonia plus platform (Biomérieux). The total turn-around time is \<2 hrs. The UR-MT is combined with standard of care, comprising: Microbiological processing per current standard of care entails culture of respiratory tract samples according to national protocols to detect respiratory bacteria, identified using biochemical methods and/or matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS). Respiratory viruses are identified using real-time PCR (for metapneumovirus, rhinovirus, influenza A, influenza B, parainfluenza 1-3, RSV and SARS-CoV-2). The total turn-around time is up to 48 hrs.

Also known as: BioFire® FilmArray® Pneumonia plus platform (Biomérieux)

Ultra-rapid molecular point-of-care testing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (aged ≥18 years),
• Clinical diagnosis of CAP (presence of at least two clinical criteria \[new/worsening cough, new/worsening expectoration of sputum, haemoptysis, new/worsening dyspnoea, pleuritic chest pain, fever, or abnormalities on chest auscultation or percussion\] or one clinical criterion and radiological evidence of CAP)
• Requiring hospitalisation to a non-ICU ward
• Capacity to give informed written consent or consent provided by the patient's legally authorized representative.

You may not qualify if:

• Pulmonary embolism
• Lung tumor
• Cystic fibrosis
• Palliative approach
• Patients who decline to provide respiratory tract specimens
• Severe immunodeficiency
• Hospitalization for two or more days in the last 14 days

Sponsors & Collaborators

• Haukeland University Hospital: lead
• University of Bergen: collaborator
• Drammen sykehus: collaborator
• University of Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator
• UMC Utrecht: collaborator
• University of Southampton: collaborator
• Quadram Institute Bioscience: collaborator

Study Sites (1)

Haukeland University Hospital

Bergen, 5098, Norway

Location

Related Publications (6)

• Saghaug CS, Markussen DL, Knoop ST, Holvik BC, Serigstad S, Ulvestad E, Ritz C, Jenum S, Grewal HMS. Diagnostic accuracy of a host response test in suspected community-Acquired pneumonia during the COVID-19 era. Int J Infect Dis. 2025 Nov;160:108045. doi: 10.1016/j.ijid.2025.108045. Epub 2025 Sep 2.

  PMID: 40907740 DERIVED

• Markussen DL, Wathne JS, Ritz C, van Werkhoven CH, Serigstad S, Bjorneklett RO, Ulvestad E, Knoop ST, Jenum S, Grewal HMS. Determinants of non-adherence to antibiotic treatment guidelines in hospitalized adults with suspected community-acquired pneumonia: a prospective study. Antimicrob Resist Infect Control. 2024 Nov 23;13(1):140. doi: 10.1186/s13756-024-01494-2.

  PMID: 39580437 DERIVED

• Markussen DL, Serigstad S, Ritz C, Knoop ST, Ebbesen MH, Faurholt-Jepsen D, Heggelund L, van Werkhoven CH, Clark TW, Bjorneklett RO, Kommedal O, Ulvestad E, Grewal HMS. Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial. JAMA Netw Open. 2024 Mar 4;7(3):e240830. doi: 10.1001/jamanetworkopen.2024.0830.

  PMID: 38446481 DERIVED

• Markussen DL, Ebbesen M, Serigstad S, Knoop ST, Ritz C, Bjorneklett R, Kommedal O, Jenum S, Ulvestad E, Grewal HMS. The diagnostic utility of microscopic quality assessment of sputum samples in the era of rapid syndromic PCR testing. Microbiol Spectr. 2023 Sep 29;11(5):e0300223. doi: 10.1128/spectrum.03002-23. Online ahead of print.

  PMID: 37772853 DERIVED

• Serigstad S, Knoop ST, Markussen DL, Ulvestad E, Bjorneklett RO, Ebbesen MH, Kommedal O, Grewal HMS. Diagnostic utility of oropharyngeal swabs as an alternative to lower respiratory tract samples for PCR-based syndromic testing in patients with community-acquired pneumonia. J Clin Microbiol. 2023 Sep 21;61(9):e0050523. doi: 10.1128/jcm.00505-23. Epub 2023 Aug 16.

  PMID: 37585220 DERIVED

• Serigstad S, Ritz C, Faurholt-Jepsen D, Markussen D, Ebbesen MH, Kommedal O, Bjorneklett RO, Heggelund L, Clark TW, van Werkhoven CH, Knoop ST, Ulvestad E, Grewal HMS; CAPNOR study group. Impact of rapid molecular testing on diagnosis, treatment and management of community-acquired pneumonia in Norway: a pragmatic randomised controlled trial (CAPNOR). Trials. 2022 Aug 1;23(1):622. doi: 10.1186/s13063-022-06467-7.

  PMID: 35915452 DERIVED

MeSH Terms

Conditions

Pneumonia; Virus Diseases

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Harleen Grewal, MD PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A pragmatic, parallel-arm, single-blinded, single-centre, randomised controlled superiority trial

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: December 9, 2020
• Study Start: September 25, 2020
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: October 26, 2023

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)