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Pulmonary CT in Pneumonia Complicating Stroke

Completed
Conditions
Stroke
Pneumonia
Registration Number
NCT03106909
Lead Sponsor
Natalie Garratt
Brief Summary

Pneumonia commonly complicates stroke and has a profound impact on clinical outcomes. Accurate and timely diagnosis of pneumonia complicating stroke remains a major challenge as several issues potentially confound diagnosis. Chest X-ray (CXR), a central component in the diagnostic work-up, may have limited utility in the early stages as they are often of suboptimal quality, and infrequently confirm typical diagnostic infiltrates. Blood biomarkers of the stress-immune response have received considerable attention, but interpretation has been limited by differing methodologies, including definition of pneumonia. Bacterial organisms in the oral cavity may also be of relevance as biomarkers of post-stroke pneumonia. Major challenges facing frontline clinicians are therefore whether to initiate antibiotics; if so, when and for how long. These issues have antibiotic stewardship implications for clinicians in terms of potential for under-treatment or over-treatment with antibiotics based on CXR appearances.

Pulmonary Computed Tomography (CT) could be of value as a radiological reference standard when pneumonia is suspected after stroke, and enable more rigorous evaluation of the diagnostic performance of CXR (and other candidate biomarkers) to inform decision-making when pneumonia is suspected.

The overall primary aim is therefore to investigate the feasibility and reliability of using pulmonary CT as a radiological reference standard for evaluating suspected pneumonia complicating stroke. The secondary aims are to explore the diagnostic accuracy of CXR and blood biomarkers (index tests) when pneumonia is suspected during hospital admission after stroke using pulmonary CT as a reference standard.

Detailed Description

Pneumonia is a frequent complication of stroke, particularly within the first few days. The risk of pneumonia is increased in patients who are older, have a more severe stroke and in those who have swallowing problems as a result of their stroke. Patients who develop pneumonia have a higher risk of death and longer hospital stay. The diagnosis of pneumonia is not always easy, but it is important to identify pneumonia early in order to begin the most appropriate treatment in a timely fashion and avoid giving antibiotics unnecessarily. Chest x-ray, the standard test undertaken when pneumonia is suspected, infrequently shows changes and is of limited value.

Pulmonary Computed Tomography (CT) scans can be used to image the lungs in more detail than a standard chest xray. The Investigators plan to assess if it is feasible to perform pulmonary CT imaging in stroke patients within 48 hours of symptoms and who may be acutely unwell. The Investigators will also investigate how reliable CT is at diagnosing pneumonia by asking different x-ray doctors to review the scans. Comparing the result of the pulmonary CT imaging to the chest x-ray will allow assessment of their utility for the diagnosis of pneumonia. The Investigators will also record whether the CT informs clinical management e.g. stopping antibiotics if pneumonia is excluded.

Blood samples will be collected for measurement of inflammatory markers and mouth swabs will measure types of bacteria. The analysis will be conducted at Salford Royal NHS Foundation Trust (SRFT) and using new cutting-edge techniques performed by collaborators at ThermoFisher and Manchester Collaborative Centre for Inflammation Research. The Investigators will assess how useful these inflammatory proteins are in pneumonia diagnosis compared to the pulmonary CT scans. This research will help the Investigating team design larger studies to diagnose pneumonia earlier and more accurately, enabling more effective use of antibiotics.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
41
Inclusion Criteria
  • Inpatient in SRFT or RSUH with diagnosis of stroke current admission
  • Within 24h of clinically suspected pneumonia occurring after admission
  • Aged ≥18y
  • Provision of informed consent from participant or personal consultee
  • Able to undergo pulmonary CT within next 48h
Exclusion Criteria
  • Treatment for lower respiratory tract infection (LRTI) completed within the preceding month
  • Mechanical ventilation planned or anticipated imminently
  • End-of-life care planned or anticipated imminently

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Proportions of eligible participants from screening; eligible participants declining participation (and reasons)18 months
Proportion of participants undergoing pulmonary CT18 months

Participants scanned and reasons for not scanning

Secondary Outcome Measures
NameTimeMethod
Proportion of consenting participants undergoing repeat CXR when indicated18 months
Proportion with changes consistent with pneumonia on CXR; proportion with changes consistent with pneumonia on pulmonary CT18 months
Proportion participants with changes consistent with pneumonia on pulmonary CT18 months
Characteristics and distribution of radiological changes consistent with pneumonia on pulmonary CT18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Spectrum of additional radiological findings on pulmonary CT18 months
Inter-rater reliability of CXR; and pulmonary CT interpretation3 months

Inter-rater reliability of the CXR reports will be evaluated using k statistics and the Bland and Altman method

Inter-rater reliability of pulmonary CT interpretation3 months

Inter-rater reliability of the pulmonary CT reports will be evaluated using k statistics and the Bland and Altman method

Proportion of participants with confirmed pneumonia18 months

Confirmed pneumonia is defined as meeting the PISCES clinical criteria AND with changes of pneumonia on pulmonary CT, agreed by an adjudication panel

Estimate and confidence intervals of sensitivity and specificity of CXR3 months

Using diagnostic odds ratio for CXR singly and with repeat CXR where indicated clinically

Estimate and confidence intervals of sensitivity and specificity of C-reactive protein (CRP) markers18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Estimate and confidence intervals of sensitivity and specificity of procalcitonin (PCT)18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Estimate and confidence intervals of sensitivity and specificity of copeptin18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Estimate and confidence intervals of sensitivity and specificity of pro-adrenomedullin (Pro-ADM)18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Estimate and confidence intervals of sensitivity and specificity of monocyte/ B-cell markers18 months

Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values

Characteristics of oral bacterial species18 months

Oral bacterial species will be compared in patients with and without confirmed pneumonia in univariate hypothesis generating analyses

Distribution of oral bacterial species18 months

Oral bacterial species will be compared in patients with and without confirmed pneumonia in univariate hypothesis generating analyses

Number of days of antibiotic treatment18 months

Trial Locations

Locations (2)

Royal Stoke University Hospital

🇬🇧

Stoke on Trent, Staffordshire, United Kingdom

Salford Royal Nhs Foundation Trust

🇬🇧

Salford, Greater Manchester, United Kingdom

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