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

• ClinicalTrials.gov Identifier: NCT04660084
• Recruitment Status: Recruiting
• First Posted: December 9, 2020
• Last Update Posted: December 9, 2020
• Sponsor: Haukeland University Hospital
• Collaborators: University of Bergen; Drammen sykehus; University of Copenhagen; Rigshospitalet, Denmark; UMC Utrecht; University of Southampton; Quadram Institute Bioscience
• Information provided by (Responsible Party): Haukeland University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pneumonia	Diagnostic Test: Ultra-rapid molecular point-of-care testing	Not Applicable

Detailed Description:

The study is a pragmatic, single-blind, single-centre randomised controlled trial (RCT) where community-acquired pneumonia (CAP) patients will receive standard of care microbiological testing or standard of care microbiological testing and comprehensive ultra-rapid molecular testing (UR-MT).

Investigators will over a 3-year period (2020-2022), consecutively enroll cases of CAP admitted (~900/year) to Haukeland University Hospital (HUS, Bergen). The study will consist of representative patients admitted with CAP and thus, will potentially be generalisable to hospitalised patients with CAP in Norway. As COVID-19 cannot be distinguished clinically from other pneumonias, the study will therefore include patients with suspected CAP, including with COVID-19. Approximately 1500 CAP patients will be screened to achieve a total of 1060 (allowing for a 10% dropout rate) enrolled patients that are randomly assigned to receive standard of care microbiological testing or standard of care testing microbiological and the comprehensive ultra-rapid molecular test (UR-MT).

Inclusion criteria for the study are: adults (aged ≥18 years), with a 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, and with a capacity to give informed written consent or consent provided by the patient's legally authorized representative.

Exclusion criteria include: lung tumour, cystic fibrosis, a palliative approach, patients who decline to provide respiratory tract specimens, severe immunodeficiency, and hospitalization for two or more days in the last 14 days.

Based on clinical evaluation and data of admission, patients will be triaged for severity according to current risk assessment guidelines, as well as the CRB-65 score for the assessment of severity of pneumonia. Randomization of CAP patients to the two treatment arms (1:1) will be performed in blocks of size 4, 6, or, 8, occurring in random order, to ensure approximately equal allocation over the year.

The prescribed empirical therapy for each patient will be compared with what antimicrobial(s) would have been appropriate for pathogen-directed therapy, based on the UR-MT result. Appropriate pathogen-directed therapy will be determined using national guidelines recommended by the Norwegian directorate of health

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1060 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Diagnostic
• Official Title: Impact of Molecular Testing on Improved Diagnosis, Treatment and Management of CAP in Norway: a Pragmatic Randomised Controlled Trial
• Actual Study Start Date: September 25, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Ultra-rapid molecular point-of-care testing; 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; 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.; Other Name: BioFire® FilmArray® Pneumonia plus platform (Biomérieux)
No Intervention: Standard of care; Standard collection of microbiological specimens and standard reply to treating staff.

Outcome Measures

Primary Outcome Measures :

1. The provision of pathogen-directed treatment based on a microbiological test result deemed as clinically relevant within 48 hours of receipt of respiratory samples. [ Time Frame: "Up to 72 hours" ]
   Binary outcome: yes: it was provided/no: it was not provided
2. Time in hours from receipt of respiratory specimens to receiving pathogen-directed treatment [ Time Frame: "Up to 72 hours" ]
   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.

Secondary Outcome Measures :

1. Duration of antibiotic use in days [ Time Frame: "Up to 4 weeks" ]
   Duration of antibiotic use in days
2. Proportion of patients receiving narrow-spectrum antibiotics within 48 hours from study inclusion [ Time Frame: "Up to 4 weeks" ]
   Proportion of patients receiving narrow-spectrum antibiotics within 48 hours from study inclusion
3. Proportion of patients receiving a single dose of antibiotics [ Time Frame: "Up to 1 week" ]
   Proportion of patients receiving a single dose of antibiotics
4. Proportion of patients receiving ≤48 h of antibiotics [ Time Frame: "Up to 1 week" ]
   Proportion of patients receiving ≤48 h of antibiotics
5. Proportion of patients receiving intravenous antibiotics [ Time Frame: "Up to 1 week" ]
   Proportion of patients receiving intravenous antibiotics
6. Duration of intravenous antibiotics in days [ Time Frame: "Up to 4 weeks" ]
   Duration of intravenous antibiotics in days
7. Proportion of cases where the UR-MT results were used to guide treatment [ Time Frame: "Up to 1 week" ]
   Proportion of cases where the UR-MT results were used to guide treatment
8. Time in days to isolation or de-isolation [ Time Frame: "Up to 2 weeks" ]
   Time in days to isolation or de-isolation
9. Duration of "door-to-needle time" in hours [ Time Frame: "Up to 1 week" ]
   Duration of "door-to-needle time" in hours
10. Length of hospital stay in days [ Time Frame: "Up to 3 months" ]
    Length of hospital stay in days
11. Proportion of 30-day readmission [ Time Frame: "Up to 30 days from discharge" ]
    Proportion of 30-day readmission
12. Proportion of 30- and 90-day and 1- and 5 year mortality [ Time Frame: "Up to 1 month, 3 months, 1 and 5 years, from admission" ]
    Proportion of 30- and 90-day and 1- and 5 year mortality

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Contacts and Locations

Contacts

Contact: Harleen Grewal, MD PhD; +4799450554; harleen.grewal@uib.no

Locations

Norway

Haukeland University Hospital; Recruiting

Bergen, Norway, 5098

Contact: Harleen Grewal, MD PhD +47 99450554 Harleen.Grewal@uib.no

Contact: Elling Ulvestad, MD PhD +47 90824574 Elling.Ulvestad@helse-bergen.no

Principal Investigator: Harleen Grewal, MD PhD

Sub-Investigator: Elling Ulvestad, MD PhD

Sub-Investigator: Rune Bjørneklett, MD PhD

Sponsors and Collaborators

Haukeland University Hospital

University of Bergen

Drammen sykehus

University of Copenhagen

Rigshospitalet, Denmark

UMC Utrecht

University of Southampton

Quadram Institute Bioscience

Investigators

• Principal Investigator: Harleen Grewal, MD PhD; Haukeland University Hospital

More Information

• Responsible Party: Haukeland University Hospital
• ClinicalTrials.gov Identifier: NCT04660084
• Other Study ID Numbers: HaukelandUH_31935
• First Posted: December 9, 2020
• Last Update Posted: December 9, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Haukeland University Hospital:

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

Additional relevant MeSH terms:

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