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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hospital-acquired Pneumonia

Intervention / Treatment
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* Diagnostic Test: CT scan
* Diagnostic Test: FilmArray Pneumonia Panel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 1: ≥ 18 years Patients with suspected HAP Stage 2: The clinician intends to treat the patient for HAP or a hospital acquired respiratory tract infection (RTI). A sputum sample can be obtained Exclusion Criteria: Stage 1: Intention to palliate rather than cure Interventions cannot be completed before administration of second antibiotic dose Cannot have low-dose, non-contrast CT scan on clinical grounds Pregnancy Previous study participation (patients with second or third episodes of HAP will not be re-recruited) Stage 2: Following the CXR or CT the clinician decides not to treat with antibiotics for either HAP or a hospital acquired RTI. A sputum sample cannot be obtained

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |