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Trial registered on ANZCTR


Registration number
ACTRN12620000954921
Ethics application status
Approved
Date submitted
30/06/2020
Date registered
25/09/2020
Date last updated
25/09/2020
Date data sharing statement initially provided
25/09/2020
Date results information initially provided
25/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Trialling a double-dose of influenza vaccine to examine the efficacy of the influenza vaccination in patients with chronic obstructive pulmonary disease (COPD)
Scientific title
Efficacy of a prime-boost, double-dose immunisation of the seasonal influenza vaccination in COPD patients.
Secondary ID [1] 301899 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
DDIVC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 318084 0
Influenza viral disease 318085 0
Condition category
Condition code
Respiratory 316112 316112 0 0
Chronic obstructive pulmonary disease
Infection 316113 316113 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Open label, interventional study of two sequential doses of seasonal influenza vaccination in COPD patients.
Initial recruitment of COPD patients via telephone contact will occur onward from January 2018, in readiness for receiving the 2018 seasonal influenza vaccine upon its availability. Study information will then be sent to potential participants via mail prior to their first study clinic visit. COPD patients will provide an initial single blood sample to be analysed of no more than 40 ml, prior to receiving a single, standard-dose (15 ug/strain) of inactivated and purified seasonal influenza vaccine, administered intra-muscularly in the deltoid by a clinical nurse. COPD patients will return 28 days post initial inoculation (p.i.), to provide a second single blood sample of no more 40 ml, prior to receiving a second single, standard-dose (15 ug/strain) of inactivated and purified seasonal influenza vaccine. COPD patients will then attend two further clinic visits to provide blood samples of no more than 40 ml at 56 days, and no more than 10 ml at 84 days post initial vaccine.
In 2018, COPD patients will be asked to attend four (4) mandatory study clinic visits, including administration of two sequential, standard, seasonal vaccines delivered 28 days apart. The duration of the first study clinic visit will be approximately two hours in which to complete study screening paperwork, signed consent forms, perform initial lung capacity testing, including a 15 minute period to assess patient reaction to vaccine. Duration of remaining study clinic visits will be approximately 45min, in which to take blood samples and assess patient health, and includes a 15 minute period to assess patient reaction to vaccine on the second visit. Participants will be telephoned to remind them of upcoming clinic visits and research nurses will maintain an attendance log to monitor participant clinic visits for follow up blood collections.
Intervention code [1] 317970 0
Treatment: Drugs
Comparator / control treatment
No control group assessed.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324303 0
Assess whether prime-boost, sequential double-dose influenza vaccine administration is able to increase antibody response relative to baseline and day 28 post initial vaccination.
Individual study participant serum antibody levels will be assessed via haemaglutination inhibition assay for specific influenza strains.
Timepoint [1] 324303 0
Baseline, 28 days, 56 days (primary endpoint), and 84 days post initial influenza vaccine
Primary outcome [2] 324314 0
Vaccine strain specific antibody titres, looking at the proportion of influenza vaccine recipients achieving ‘seroconversion’ (defined as a 4-fold increase in HI titre from baseline), at day 56 post initial vaccination.
Study participant serum antibody levels will be assessed via haemaglutination inhibition assay for specific influenza strains
Timepoint [2] 324314 0
Baseline, 28 days, 56 days (primary endpoint), and 84 days post initial influenza vaccine.
Primary outcome [3] 324898 0
Vaccine strain specific antibody titres, looking at the proportion of influenza vaccine recipients achieving ‘seroprotection’ (defined as haemagglutination inhibition antibody (HI) titre greater-than-or-equal-to 1:40) at day 56 post initial vaccination. Individual study participant serum antibody levels will be assessed via haemaglutination inhibition assay for specific influenza strains
Timepoint [3] 324898 0
Baseline, 28 days, 56 days (primary endpoint), and 84 days post initial influenza vaccine.
Secondary outcome [1] 384291 0
Proportion of strain-specific B-cells induced by influenza vaccination, Assessment of B-cell type and quantification will be via flow cytometry.
Timepoint [1] 384291 0
Baseline, 28 days, and 56 days post initial influenza vaccine.
Secondary outcome [2] 384292 0
Phenotypic changes in memory B-cells, induced by influenza vaccination. Assessment of B-cell type and quantification will be via flow cytometry.
Timepoint [2] 384292 0
Baseline, 28 days, and 56 days post initial influenza vaccine.
Secondary outcome [3] 386190 0
Ability of prime-boost, sequential double-dose influenza vaccine administration is able to extend antibody response.
Individual study participant serum antibody levels will be assessed via haemaglutination inhibition assay for specific influenza strains
Timepoint [3] 386190 0
Baseline, 28 days, 56 days, and 84 days 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 0.8.
COPD patients will be stable with no COPD exacerbations or respiratory infections within the 4 weeks prior to participating in the study.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Invasive malignancy within the last 2 years.
Renal impairment (eGFR less than 40 ml/min).
Acute febrile illness with fever greater than 38.5 degrees Celsius.
Hypersensitivity to egg protein.
Use of oral Prednisolone or equivalent. greater than or equal to 10 mg 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
Non-stable cardiac disease, non-stable diabetes mellitus, and some skin cancers as assessed by the principal investigator,

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
All outcomes will be presented using descriptive statistics; normally distributed data by the mean and standard deviation (SD) and skewed distributions by the geometric mean and 95% confidence intervals (CI). Binary and categorical variables will be presented using counts and percentages.
Primary analysis
The primary analysis will compare HI titres from baseline to days 28, 56 and 84 post initial vaccine using non-parametric analyses, or HI data will be log-transformed and assessed using standard parametric methods for differences between means. Data will be presented as geometric mean titre including 95% CI. Variables will be used in correlation analyses against post vaccination titres.
Secondary analysis
Variables influencing seroconversion (a greater-than-or-equal-to 4-fold difference in HI titre from baseline to day post initial vaccination) or seroprotection (a post vaccination HI titre greater-than-or-equal-to 1:40) will be assessed with GLM analyses, using seroconversion or seroprotection as the dependant variable. Percentage induction of strain specific B-cells on days post initial vaccination, and percentage change in B-cell phenotypes on days post initial vaccination will be assessed using non-parametric rank sum tests.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 17014 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 17015 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 30678 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 30679 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 306090 0
Government body
Name [1] 306090 0
National Health and Medical Research Council
Address [1] 306090 0
16 Marcus Clarke street
Canberra, ACT, 2601
Country [1] 306090 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
199 Ipswitch Rd
Woolloongabba, QLD, 4102
Country
Australia
Secondary sponsor category [1] 306559 0
University
Name [1] 306559 0
The University of Queensland
Address [1] 306559 0
Brisbane, St Lucia, QLD, 4072
Country [1] 306559 0
Australia
Other collaborator category [1] 281375 0
Hospital
Name [1] 281375 0
Royal Melbourne Hospital
Address [1] 281375 0
300 Grattan St, Parkville, Melbourne, Victoria, 3050
Country [1] 281375 0
Australia
Other collaborator category [2] 281376 0
University
Name [2] 281376 0
University of Melbourne
Address [2] 281376 0
Department of Pharmacology and Therapeutics,
Medical Sciences Building, Building 181,
Reception Level 2 west wing,
Corner Grattan and Royal Parade,
Parkville, Victoria 3010
Country [2] 281376 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306310 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 306310 0
Metro South Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 306310 0
Australia
Date submitted for ethics approval [1] 306310 0
21/12/2009
Approval date [1] 306310 0
25/03/2010
Ethics approval number [1] 306310 0
HREC/09/QPAH/297

Summary
Brief summary
It has been suggested that people with chronic obstructive pulmonary disease (COPD) 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. As little is known about the efficacy of influenza vaccine in COPD, this pilot study will examine the effect of two sequential doses of the seasonal influenza vaccination in those with COPD, and whether this higher vaccine dose is able to augment the immune response in COPD patients. Outcomes will focus on antibody response and the factors that predict an effective antibody response to the vaccine.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103458 0
Prof John W Upham
Address 103458 0
The University of Queensland, Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 103458 0
Australia
Phone 103458 0
+617 3443 8024
Fax 103458 0
Email 103458 0
j.upham@uq.edu.au
Contact person for public queries
Name 103459 0
Prof John W Upham
Address 103459 0
The University of Queensland, Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 103459 0
Australia
Phone 103459 0
+617 3443 8024
Fax 103459 0
Email 103459 0
j.upham@uq.edu.au
Contact person for scientific queries
Name 103460 0
Prof John W Upham
Address 103460 0
The University of Queensland, Diamantina Institute
Translational Research Institute
37 Kent Street
Woolloongabba, QLD 4102
Country 103460 0
Australia
Phone 103460 0
+617 3443 8024
Fax 103460 0
Email 103460 0
j.upham@uq.edu.au

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary