Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000830998
Ethics application status
Approved
Date submitted
21/05/2020
Date registered
21/08/2020
Date last updated
21/08/2020
Date data sharing statement initially provided
21/08/2020
Date results information initially provided
21/08/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Using influenza vaccination to understand and improve immune responses to vaccination in patients with chronic obstructive pulmonary disease (COPD) and healthy older people.
Scientific title
Immunogenicity of the influenza vaccination in patients with chronic obstructive pulmonary disease (COPD).
Secondary ID [1] 301265 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
IVC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 317435 0
Influenza viral disease 317436 0
Condition category
Condition code
Respiratory 315530 315530 0 0
Chronic obstructive pulmonary disease
Infection 315531 315531 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
Open label, observational study of seasonal influenza vaccination in COPD patients and healthy age-matched control subjects.
COPD patients will be recruited over three (3) seasonal influenza vaccine years, with each year considered a separate cohort. Some patients will be repeat participants, however, they will be considered individual participants for separate years due to differences in age and physical parameters that occur in the course of one year. COPD patients will provide an initial single blood sample to be analysed of no more than 50ml, prior to receiving a single standard dose of inactivated and purified influenza vaccine in autumn of 2015, 2016, 2017. COPD patients will provide further single blood samples 24h post inoculation (p.i.) of no more 2.5ml, 7 and 28 days p.i. of no more than 40ml and 90 day p.i. of no more than 10ml.
COPD patients will be asked to attend three (3) mandatory study clinic visits, including administration of seasonal vaccine, with a additional 2 study clinic visits (days 7 and 90 p.i) being optional.
Intervention code [1] 317568 0
Diagnosis / Prognosis
Comparator / control treatment
Control group in observational study were healthy age-matched participants. All participants received the seasonal influenza vaccine as standard of care.
Healthy participants will be recruited over three (3) seasonal influenza vaccine years, with each year considered a separate cohort. Some participants will be repeat participants, however, they will be considered individual participants for separate years due to differences in age and physical parameters that occur in the course of one year. Healthy participants will provide an initial single blood sample to be analysed of no more than 50 ml, prior to receiving a single standard dose of inactivated and purified influenza vaccine in autumn of 2015, 2016, 2017. Healthy participants will provide further single blood samples 24 h post inoculation (p.i.) of no more 2.5 ml, 7 and 28 days p.i. of no more than 40 ml and 90 day p.i. of no more than 10 ml.
Healthy participants will be asked to attend three (3) mandatory study clinic visits, including administration of seasonal vaccine, with an additional 2 study clinic visits (days 7 and 90 p.i) being optional.
Control group
Active

Outcomes
Primary outcome [1] 323778 0
Proportion of influenza vaccine recipients achieving antibody levels that connote protection against specific influenza vaccine antibody strains. Individual study participant serum antibody levels will be assessed via haemaglutination inhibition assay for specific influenza strains.
Timepoint [1] 323778 0
Baseline, 24hrs, 7 days, 28 days and 90 days post initial influenza vaccine.
Secondary outcome [1] 382857 0
Measure cellular phenotype, in particular dendritic, B-cell and T-cell populations, to identify differences between COPD and healthy participants in response to influenza vaccine.
Changes in immune cell numbers will be assessed by flow cytometry. To determine the quantity and isotype of B cells elicited, influenza-specific B cells were identified using recombinant HA (rHA) probes and assessed by flow cytometry
Timepoint [1] 382857 0
Baseline, 24hrs, 7 days, 28 days and 90 days post initial Influenza Vaccine.
Secondary outcome [2] 384297 0
Identification of deferentially expressed genes that differ between COPD and healthy participants in response to the influenza vaccine, via RNASeq.
Timepoint [2] 384297 0
Baseline, and 24hrs post initial influenza vaccine.

Eligibility
Key inclusion criteria
Mild to very Severe COPD with a post bronchiodilater FEV1 less than 80% predicted FEV1 /FVC ratio less than 0.7. COPD patients will be stable with no COPD exacerbations or respiratory infections within the last 4 weeks.
Healthy controls no prior or current symptoms of lung disease, MRC dyspnoea scale less than 2 and normal spirometry. And normal spirometry with an FEV1 and FVC within normal range.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Invasive malignancy within the last 2 years.
Renal impairment (eGFR less than 40ml/min).
Acute febrile illness with fever greater than 38.5 dC.
Hypersensitivity to egg protein.
Use of oral Prednisolone (or equivalent) greater than or equal to 10mg per day.
Use of other systemic immunosuppressive therapy.
Anaphylaxis following a previous dose of influenza vaccine.
Anaphylaxis following a vaccine component (including eggs).
History of Guilliane Barre within 6 weeks of a previous influenza vaccination

Cardiac disease, diabetes mellitus and superficial non- melanoma skin cancers WILL NOT be exclusion criteria provided these are stable and well controlled in the opinion of the investigator.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Based on pilot data, a sample size of 36 COPD patients and 36 control subjects in each age strata (56-64 years, 65-74 years, and over 75 years) has a power of 90% to detect a difference between patients and controls in post-vaccination antibody titre at a significance level of 0.05. Thus a total of 108 COPD and 108 Control subjects will need to complete the study. On the assumption that 20% of participants will fail to attend one or more of the scheduled blood collections, we estimate that 135 COPD patients and 135 control subjects will need to be recruited.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
13/04/2015
Date of last participant enrolment
Anticipated
Actual
8/06/2017
Date of last data collection
Anticipated
Actual
30/08/2017
Sample size
Target
216
Accrual to date
Final
171
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 16653 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 16654 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 16656 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 30249 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 30250 0
3050 - Parkville
Recruitment postcode(s) [3] 30252 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 305713 0
Government body
Name [1] 305713 0
National Health and Medical Research Council
Country [1] 305713 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
199 Ipswitch Rd
Woolloongabba, QLD, 4102
Country
Australia
Secondary sponsor category [1] 306130 0
University
Name [1] 306130 0
The University of Queensland
Address [1] 306130 0
Brisbane, St Lucia, QLD, 4072
Country [1] 306130 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305988 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 305988 0
Metro South Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 305988 0
Australia
Date submitted for ethics approval [1] 305988 0
21/12/2009
Approval date [1] 305988 0
25/03/2010
Ethics approval number [1] 305988 0
HREC/09/QPAH/297
Ethics committee name [2] 306050 0
UQ Human Ethics, Research Management Office
Ethics committee address [2] 306050 0
Research Management Office,
UQ Research and Innovation,
The University of Queensland, Brisbane Queensland 4072
Ethics committee country [2] 306050 0
Australia
Date submitted for ethics approval [2] 306050 0
05/02/2015
Approval date [2] 306050 0
13/02/2015
Ethics approval number [2] 306050 0
2011000502

Summary
Brief summary
Influenza infection is a frequent and important problem in chronic obstructive pulmonary disease (COPD). Influenza can have severe consequences in these patients, leading to acute exacerbations of COPD, pneumonia and respiratory failure. COPD patients are thus recognised as a group at particular risk of influenza, and current guidelines recommend yearly influenza vaccination. These recommendations are largely based on expert opinion and observational studies, with very few randomised controlled trials having been conducted in COPD. It has been suggested that people with COPD may have an aberrant immune response to influenza viruses, and as such, they may be less able to effectively mount an immune response to influenza vaccination. This study will examine influenza vaccination in people with COPD, and healthy age-matched controls, focussing on the factors that predict an effective antibody response to the vaccine (seroprotection), especially aspects of dendritic cell and T-cell function.
We will conduct an open-label observational study of seasonal influenza vaccine in 108 COPD patients and 108 healthy, age-matched control subjects. Subjects will receive a single dose of inactivated and purified split influenza vaccine in the autumn of 2015, 2016 and 2017. Primary outcomes of this study will be the proportion of vaccine recipients who achieve seroprotection or seroconversion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102326 0
Prof John W Upham
Address 102326 0
The University of Queensland Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 102326 0
Australia
Phone 102326 0
+617 3443 8024
Fax 102326 0
Email 102326 0
[email protected]
Contact person for public queries
Name 102327 0
John W Upham
Address 102327 0
The University of Queensland Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 102327 0
Australia
Phone 102327 0
+617 3443 8024
Fax 102327 0
Email 102327 0
[email protected]
Contact person for scientific queries
Name 102328 0
John W Upham
Address 102328 0
The University of Queensland Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 102328 0
Australia
Phone 102328 0
+617 3443 8024
Fax 102328 0
Email 102328 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data for individual patients will not be available publicly due to ethical restrictions. Combined data for the trial will be publicly available.


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
SourceTitleYear of PublicationDOI
EmbaseVaccine strain affects seroconversion after influenza vaccination in COPD patients and healthy older people.2022https://dx.doi.org/10.1038/s41541-021-00422-4
N.B. These documents automatically identified may not have been verified by the study sponsor.