Clinical trial NCT05483309: Feasibility Study of Contemporary Diagnostics for Patients With Suspected Hospital-Acquired Pneumonia.
Official title: Feasibility Study of the Clinical and Cost-effectiveness of Contemporary Diagnostics for Patients With Suspected Hospital-Acquired Pneumonia (HAP).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hospital-acquired Pneumonia
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2022-08-02
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Hospital-Acquired Pneumonia (HAP) is a severe lung infection that develops while a patient is in hospital. We aim to design a trial to see if modern diagnostic investigations can safely improve outcomes for patients suspected of HAP.

Currently, doctors use chest x-rays to make the diagnosis, but these are difficult to interpret and a third of patients suspected of HAP receive antibiotics inappropriately. Patients are concerned about misdiagnosis and a solution might be to replace the chest x-ray with a CT scan since these show the lungs in more detail.

Once a diagnosis of HAP is made, doctors would like to identify the bacteria or viruses responsible. However, current tests are too slow to determine the initial treatment, so guidelines suggest we cover a range of possibilities with two extended spectrum antibiotics. Patients tell us they are concerned, because these antibiotics increase the risk of severe side effects and promote antibiotic resistance. The BIOFIRE® FILMARRAY® pneumonia panel (FAPP) is a new test that can identify the cause of HAP quickly. If we can determine the best way to use the FAPP, we can give antibiotics more effectively and slow the development of antimicrobial resistance.

We will conduct a feasibility study to inform the design of a fully powered trial to discover whether using CT scans or the FAPP, or both together, helps improve antibiotic use and patient recovery whilst being cost effective.

We will interview some participants and staff about how the trial is working so that we can improve the design. We will list the costs associated with HAP so we can design a cost effectiveness evaluation for the definitive trial. We will use patient samples to investigate immune and inflammation related processes to better understand why some people develop HAP and why some become particularly unwell.


Eligibility criteria: Inclusion Criteria:

Stage 1:

* Age ≥ 18 years
* Suspected HAP\*

For the purposes of this study, HAP is defined as per the BTS and FDA definitions i.e. pneumonia which develops 48 hours after an admission to hospital for an alternative diagnosis; or a new presentation to hospital with pneumonia in a patient who has been discharged from an overnight stay in hospital within the last 10 days.

Stage 2:

* The clinician intends to treat the patient for HAP or a hospital acquired respiratory tract infection (RTI).
* A sputum sample has been obtained before 2nd dose of antibiotic.

Exclusion Criteria:

Stage 1:

* Already received a chest X-ray to confirm suspected HAP diagnosis
* Diagnosis or suspected diagnosis of ventilator acquired pneumonia
* Intention to palliate rather than cure
* Interventions cannot be completed before administration of second antibiotic dose\*
* Cannot be randomised to low-dose, non-contrast CT scan on clinical grounds e.g. strong suspicion of PE\*\*
* Pregnancy\*\*\*
* Previous study participation (patients with second of third episodes of HAP will not be re-recruited)

In the circumstance where a patient is diagnosed with HAP whist receiving antibiotics for a non-respiratory infection e.g. cellulitis or UTI, if the HAP diagnosis leads to a change in the antibiotic prescription to cover the HAP then that patient will be eligible for recruitment. However, if the diagnosis of HAP does not result in a change in antibiotic then the patient is not eligible.

A non-contrast, low-dose thoracic CT scan is an inappropriate test for a PE and if that is high in the differential diagnosis then tick yes here.

A urine pregnancy test is required as part of routine care prior to a chest X-ray or CT scan. If the test reveals the patient is pregnant, they will not be eligible for the study as they will be unable to receive a CT scan as part of this study. Pregnancy tests are not required at future time points.

Stage 2:

- Following the CXR or CT the clinician decides not to treat with antibiotics for either HAP or a hospital acquired RTI.

Primary outcomes:
measure: Determine the feasibility of a full-scale Randomised Controlled Trial (RCT) comparing different diagnostic dynamic treatment regimens (DTRs) in adult patients suspected of HAP.
timeFrame: Screening and randomisation (1 year); follow up (3 months); end of study analysis (9 months).
Secondary outcomes:
measure: Estimate population statistics for each DTR - Time to clinical cure
timeFrame: Day 90
measure: Estimate population statistics for each DTR - Antibiotic usage
timeFrame: Day 90
measure: Estimate population statistics for each DTR - Change to Quality of Life
timeFrame: Baseline, day 10, 28 and 90
measure: Estimate population statistics for each DTR - Length of hospital stay
timeFrame: Day 90
measure: Estimate population statistics for each DTR - Mortality
timeFrame: Day 14, 28 and 90
measure: Estimate number of eligible patients and the pattern of their presentation.
timeFrame: At end of study (15 months)
measure: Estimate rates of successful follow up.
timeFrame: At end of study (15 months)
measure: Estimate rates of completion of questionnaires.
timeFrame: At end of study (15 months)
measure: Test the web-based randomisation process and incorporate clinical and researcher feedback.
timeFrame: During qualitative analysis throughout the study (up to 15 months)
measure: Perform a costing analysis of HAP to inform the cost-effectiveness analysis for any definitive trial.
timeFrame: At end of study (15 months)
measure: Assess human factors involved in delivery of the study and how the different diagnostic tests influence clinical decision making by conducting qualitative interviews and focus groups with healthcare workers and researchers.
timeFrame: During qualitative analysis throughout the study (up to 15 months)
measure: Evaluate willingness of clinicians to recruit to the study.
timeFrame: During qualitative analysis throughout the study (up to 15 months)
measure: Evaluate willingness of potential participants or their consultees to be recruited.
timeFrame: During qualitative analysis throughout the study (up to 15 months)
measure: Evaluate adherence to antibiotic guidelines and study protocol.
timeFrame: At end of study (15 months)
measure: Assess the study participant and carer experience of participating in the study.
timeFrame: During qualitative analysis throughout the study (up to 15 months)
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Preston
country: United Kingdom
facility: Lancashire teaching hospitals NHS Foundation Trust
Study officials:
References: