Feasibility Study of Contemporary Diagnostics for Patients With Suspected Hospital-Acquired Pneumonia.

Hospital-acquired Pneumonia Clinical Trial

— HAP-FAST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05483309
• Other study ID #: UoL001676
• Status: Recruiting
• Phase: N/A
• Start date: June 13, 2023
• Est. completion date: May 2024

Study information

• Verified date: January 2024
• Source: University of Liverpool
• Contact: Daniel Wootton
• Phone: 0151 529 3796
• Email: dwootton[@]liverpool.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Hospital-acquired Pneumonia
• Pneumonia

Intervention

Diagnostic Test:
• CT scan
Patients receive a CT scan
• FilmArray Pneumonia Panel
The FilmArray Pneumonia Panel is used to analysis the patient's sputum sample for the cause of the hospital acquired pneumonia

Locations

Country	Name	City	State
United Kingdom	Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	Lancashire teaching hospitals NHS Foundation Trust	Preston

Sponsors (2)

Lead Sponsor	Collaborator
University of Liverpool	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Estimate population statistics for each DTR - Antibiotic usage	Antibiotic usage for the HAP episode	Day 90
Secondary	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
Secondary	Estimate population statistics for each DTR - Length of hospital stay	Length of hospital stay post HAP diagnosis.	Day 90
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Estimate rates of completion of questionnaires.	EQ5D5L, CAP-sym, economic evaluation.	At end of study (15 months)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Assess the study participant and carer experience of participating in the study.	Qualitative interviews.	During qualitative analysis throughout the study (up to 15 months)