Feasibility Study of Contemporary Diagnostics for Patients With Suspected Hospital-Acquired Pneumonia. (HAP-FAST)

Feasibility Study of the Clinical and Cost-effectiveness of Contemporary Diagnostics for Patients With Suspected Hospital-Acquired Pneumonia (HAP).

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.

Study Overview

• Status: Completed
• Conditions: Hospital-acquired Pneumonia
• Intervention / Treatment: Diagnostic test: FilmArray Pneumonia Panel; Diagnostic test: CT scan

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L69 7BE
    • Liverpool University Hospitals NHS Foundation Trust
  • Manchester, United Kingdom
    • Manchester University NHS Foundation Trust
  • Preston, United Kingdom
    • Lancashire Teaching Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic Treatment Regimen 1; Patients will receive a chest x-ray and their sputum sample will be analysed using the FilmArray Pneumonia Panel.	Diagnostic test: FilmArray Pneumonia Panel; The FilmArray Pneumonia Panel is used to analysis the patient's sputum sample for the cause of the hospital acquired pneumonia
No Intervention: Diagnostic Treatment Regimen 2; Patients will receive a chest x-ray and their sputum sample will not be analysed using the FilmArray Pneumonia Panel.
Experimental: Diagnostic Treatment Regimen 3; Patients will receive a CT scan and their sputum sample will be analysed using the FilmArray Pneumonia Panel.	Diagnostic test: FilmArray Pneumonia Panel; The FilmArray Pneumonia Panel is used to analysis the patient's sputum sample for the cause of the hospital acquired pneumonia; Diagnostic test: CT scan; Patients receive a CT scan
Experimental: Diagnostic Treatment Regimen 4; Patients will receive a CT scan and their sputum sample will not be analysed using the FilmArray Pneumonia Panel.	Diagnostic test: CT scan; Patients receive a CT scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the feasibility of a full-scale Randomised Controlled Trial (RCT) comparing different diagnostic dynamic treatment regimens (DTRs) in adult patients suspected of HAP.	Rate of recruitment; proportion screened that meet eligibility criteria; proportion eligible that consent and where they present; proportion consented and randomised that complete study pathway as per protocol; proportion consented and randomised that withdraw from trial intervention or follow up.	Screening and randomisation (1 year); follow up (3 months); end of study analysis (9 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate population statistics for each DTR - Time to clinical cure	Time to clinical cure, defined as the number of days from baseline when there is a combination of resolution of signs and symptoms present at enrolment and improvement or lack of progression of radiological signs.	Day 90
Estimate population statistics for each DTR - Antibiotic usage	Antibiotic usage for the HAP episode	Day 90
Estimate population statistics for each DTR - Change to Quality of Life	Change of quality of life using the EQ-5D-5L measure	Baseline, day 10, 28 and 90
Estimate population statistics for each DTR - Length of hospital stay	Length of hospital stay post HAP diagnosis.	Day 90
Estimate population statistics for each DTR - Mortality	We will evaluate the best way to record this by analysing: in-hospital mortality, survival at three timepoints.	Day 14, 28 and 90
Estimate number of eligible patients and the pattern of their presentation.	Hospital/ward type, time of day/day of week.	At end of study (15 months)
Estimate rates of successful follow up.	Participants who attend 28 day visit and complete the post discharge indirect cost survey at 90 days.	At end of study (15 months)
Estimate rates of completion of questionnaires.	EQ5D5L, CAP-sym, economic evaluation.	At end of study (15 months)
Test the web-based randomisation process and incorporate clinical and researcher feedback.	Qualitative conclusions based on staff focus groups.	During qualitative analysis throughout the study (up to 15 months)
Perform a costing analysis of HAP to inform the cost-effectiveness analysis for any definitive trial.	Summary statistics for numbers and types of costs with comparison between DTRs.	At end of study (15 months)
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.	Qualitative conclusions based on staff focus groups.	During qualitative analysis throughout the study (up to 15 months)
Evaluate willingness of clinicians to recruit to the study.	Qualitative conclusions based on staff focus groups.	During qualitative analysis throughout the study (up to 15 months)
Evaluate willingness of potential participants or their consultees to be recruited.	Qualitative conclusions based on participant and carer interviews.	During qualitative analysis throughout the study (up to 15 months)
Evaluate adherence to antibiotic guidelines and study protocol.	Summary statistics relating to antibiotic use in the pilot study with a comparison between the DTRs.	At end of study (15 months)
Assess the study participant and carer experience of participating in the study.	Qualitative interviews.	During qualitative analysis throughout the study (up to 15 months)

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: National Institute for Health Research, United Kingdom

Publications and helpful links

General Publications

• Shafiqa N, Aston S, Howard A, Turtle L, Abrams S, Young B, Sherratt F, Alvarez Nishio A, Wilshaw S, Jones AP, Wootton DG. HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE(R) FILM ARRAY(R) pneumonia plus panel in adults with suspected non-ventilator-associated hospital-cquired pneumonia. BMJ Open. 2024 Jul 4;14(7):e088490. doi: 10.1136/bmjopen-2024-088490.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Actual): June 11, 2025
• Study Completion (Actual): June 11, 2025

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Healthcare-Associated Pneumonia; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Tomography, X-Ray Computed
• Other Study ID Numbers: UoL001676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes