Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001721897
Ethics application status
Approved
Date submitted
14/07/2021
Date registered
16/12/2021
Date last updated
17/11/2022
Date data sharing statement initially provided
16/12/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
ImmuneCAP: Immune responses in severe community acquired pneumonia
Scientific title
ImmuneCAP: Tissue-resident memory T cell response in severe community acquired pneumonia
Secondary ID [1] 304773 0
None
Universal Trial Number (UTN)
Trial acronym
ImmuneCAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Community Acquired Pneumonia 322827 0
Sepsis 322828 0
COVID-19 323438 0
Condition category
Condition code
Respiratory 320417 320417 0 0
Other respiratory disorders / diseases
Infection 320991 320991 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We will analyse tissue samples (blood and bronchial washings) of patients with severe community acquired pneumonia (CAP) and compare these with patients without CAP. Samples will be collected during the intensive care admission by an appropriately trained intensive care doctor or nurse within 72 hours of intubation. Bronchial washings will be collected via a formal bronchoscope if clinically indicated or by passing a catheter through an endotracheal tube and introducing and aspirating a small amount of sterile saline solution (10-20ml). Blood samples will be collected via a central line, arterial line or via venesection when clinically indicated. Outcomes will be assessed at discharge from hospital via the electronic patient record with no further participant involvement post discharge.
Intervention code [1] 321155 0
Diagnosis / Prognosis
Comparator / control treatment
Control groups will be participants with non infective causes of lung inflammation and participants without infection or lung inflammation
Control group
Active

Outcomes
Primary outcome [1] 328250 0
Survival as determined by review of the electronic patient record
Timepoint [1] 328250 0
Hospital discharge
Primary outcome [2] 328768 0
Tissue resident memory response as determined by flow cytometry
Timepoint [2] 328768 0
At time of sample collection within 72 hour of intubation
Secondary outcome [1] 398252 0
Days free of mechanical ventilation as determined by review of the electronic patient record
Timepoint [1] 398252 0
28 days post initial intubation
Secondary outcome [2] 400271 0
Acute Physiology and Chronic Health Evaluation (APACHE) Score assessed via the electronic patient record
Timepoint [2] 400271 0
24 hours after admission to Intensive Care
Secondary outcome [3] 401978 0
PaO2 in mmHg/FiO2 as fraction of 1.0 (lowest) as determined by review of the electronic patient record
Timepoint [3] 401978 0
in first 72 hours of admission
Secondary outcome [4] 401979 0
Sequential Organ Failure Assessment Score as assessed by review of the electronic patient record
Timepoint [4] 401979 0
At time of sample acquisition within 72 hours of intubation
Secondary outcome [5] 401980 0
Bronchial washing mRNA analysis
Timepoint [5] 401980 0
At time of sample acquisition within 72 hours of intubation
Secondary outcome [6] 403709 0
Peripheral blood mRNA analysis
Timepoint [6] 403709 0
At time of sample acquisition within 72 hours of intubation

Eligibility
Key inclusion criteria
Admitted to a critical care setting
• A diagnosis of community acquired pneumonia has been made by the treating physicians
based on the following criteria;
- Symptoms and/or signs consistent with a lower respiratory tract infection
- Radiological evidence of new onset consolidation on a chest x-ray or CT scan
• Mechanically ventilated for less than 72 hours
• Age equal to or greater than 18 years old
• Participant consent or person responsible consent
• Patients with confirmed COVID-19 disease meeting the criteria for CAP will be included in
the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously included in the study

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
Associations between wet-lab data and clinical parameters will be determined by Spearman’s Correlation. RNA will be analysed using the Nanostring nCounter
Sprint machine and RNA panels analysed using the nSolver (Nanostring, Seattle, USA) and g:profiler software (https://biit.cs.ut.ee/gprofiler/) to generate volcano plots and Pathway Analysis “Manhattan plots”, respectively. Single-cell protein-RNA analysis will be analysed on the BD machine and using the in-built pipeline

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/08/2021
Date of last participant enrolment
Anticipated
1/08/2026
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
75
Accrual to date
31
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19963 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 19964 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 19965 0
Prince of Wales Private Hospital - Randwick
Recruitment postcode(s) [1] 34671 0
2065 - St Leonards
Recruitment postcode(s) [2] 34672 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 34673 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 309144 0
Charities/Societies/Foundations
Name [1] 309144 0
Intensive Care Foundation Australia and New Zealand
Country [1] 309144 0
Australia
Funding source category [2] 309148 0
University
Name [2] 309148 0
University of New South Wales
Country [2] 309148 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 5, 1 King Street
Newtown 2042
NSW, Australia
Country
Australia
Secondary sponsor category [1] 310098 0
None
Name [1] 310098 0
Address [1] 310098 0
Country [1] 310098 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309010 0
Northern Sydney Local Health District
Ethics committee address [1] 309010 0
NSLHD Research Office, Level 13 Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065
Ethics committee country [1] 309010 0
Australia
Date submitted for ethics approval [1] 309010 0
04/08/2020
Approval date [1] 309010 0
17/09/2020
Ethics approval number [1] 309010 0
2020/ETH00047

Summary
Brief summary
Community acquired pneumonia (CAP) is an infection of the lungs where the lungs become inflamed. CAP is most commonly caused by bacterial infections however during the seasonal ‘flu epidemics and novel pandemics such as COVID-19, viral infections may predominate. Severe CAP requires treatment in an intensive care unit (ICU) and often support of breathing with a ventilator. In Australia pneumonia is the most common infection treated in ICU and unfortunately often proves fatal. Additionally, there is a large economic cost and survivors are often left with significant reductions in their quality of life.

The body’s immune responses in the lung is designed to kill and eliminate the bacteria or viruses causing the infection but can also cause collateral damage to the lung through inflammation and injury. the lung has specialised immune cells called Tissue Resident Memory T-cells, (TRM)that play a crucial role in protecting the lung against bacteria and viruses. As the name suggests this specialised type of immune cells are ‘resident’ in the lung tissues and are not detected in the circulating blood. In this preliminary study we will evaluate a system to collect and study TRM -cells in mechanically ventilated patients with severe CAP. We will compare the immune responses of patients with severe CAP caused by COVID-19, other viral infections and bacterial infections. We will also compare patients with severe CAP to two different control groups. The first control group will be mechanically ventilated patients with lung injury not caused by infection. The second control group will be mechanically ventilated patients without evidence of lung injury.

Studying the local immune response in this way will offer insights into how severe CAP occurs, may help identify which patients are going to need to most support and may identify new treatments for this important condition.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112638 0
Dr Christopher Andersen
Address 112638 0
Intensive Care Department
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 112638 0
Australia
Phone 112638 0
+61294632580
Fax 112638 0
Email 112638 0
[email protected]
Contact person for public queries
Name 112639 0
Dr Christopher Andersen
Address 112639 0
Intensive Care Department
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 112639 0
Australia
Phone 112639 0
+61294632580
Fax 112639 0
Email 112639 0
[email protected]
Contact person for scientific queries
Name 112640 0
Dr Christopher Andersen
Address 112640 0
Intensive Care Department
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 112640 0
Australia
Phone 112640 0
+61294632580
Fax 112640 0
Email 112640 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data may be shared following approval from the study management team
When will data be available (start and end dates)?
At the conclusion of the recruitment and follow up period, anticipated to be 01/08/2024, the data will be retained for a minimum of 5 years as per institutional requirements
Available to whom?
Non commercial researchers with appropriate Human Research Ethics Committee approval
Available for what types of analyses?
Database analyses
How or where can data be obtained?
By contacting the study coordinator via The George Institute for Global Health
[email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.