Clinical trial NCT04660084: Impact of Molecular Testing on Improved Diagnosis, Treatment and Management of CAP
Official title: Impact of Molecular Testing on Improved Diagnosis, Treatment and Management of CAP in Norway: a Pragmatic Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Pneumonia
Keywords: Microbiology
Bacteria and viruses
Rapid diagnosis
Antibiotic resistance
Diagnostic stewardship
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: University of Bergen
name: Drammen sykehus
name: University of Copenhagen
name: Rigshospitalet, Denmark
name: UMC Utrecht
name: University of Southampton
name: Quadram Institute Bioscience
First posted: 2020-12-09
Enrollment: 374
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A pragmatic, parallel-arm, single-blinded, single-centre, randomised controlled superiority trial
Primary purpose: DIAGNOSTIC

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.

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

Eligibility 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

Primary outcomes:
measure: The provision of pathogen-directed treatment based on a microbiological test result deemed as clinically relevant within 48 hours of receipt of respiratory samples.
timeFrame: "Up to 72 hours"
measure: Time in hours from receipt of respiratory specimens to receiving pathogen-directed treatment
timeFrame: "Up to 72 hours"
Secondary outcomes:
measure: Duration of antibiotic use in days
timeFrame: "Up to 4 weeks"
measure: Proportion of patients receiving narrow-spectrum antibiotics within 48 hours from study inclusion
timeFrame: "Up to 4 weeks"
measure: Proportion of patients receiving a single dose of antibiotics
timeFrame: "Up to 1 week"
measure: Proportion of patients receiving ≤48 h of antibiotics
timeFrame: "Up to 1 week"
measure: Proportion of patients receiving intravenous antibiotics
timeFrame: "Up to 1 week"
measure: Duration of intravenous antibiotics in days
timeFrame: "Up to 4 weeks"
measure: Proportion of cases where the UR-MT results were used to guide treatment
timeFrame: "Up to 1 week"
measure: Time in days to isolation or de-isolation
timeFrame: "Up to 2 weeks"
measure: Duration of "door-to-needle time" in hours
timeFrame: "Up to 1 week"
measure: Length of hospital stay in days
timeFrame: "Up to 3 months"
measure: Proportion of 30-day readmission
timeFrame: "Up to 30 days from discharge"
measure: Proportion of 30- and 90-day and 1- and 5 year mortality
timeFrame: "Up to 1 month, 3 months, 1 and 5 years, from admission"
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Harleen Grewal, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.