ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12614001003662

Ethics application status

Approved

Date submitted

2/09/2014

Date registered

17/09/2014

Date last updated

14/07/2016

Type of registration

Prospectively registered

Titles & IDs

Public title

Efficacy and safety of Prevenar 13 in people with asthma

Scientific title

A single-site trial to investigate the efficacy, safety and immunogenicity of conjugated pneumococcal vaccine
(CJPV13, Prevenar) on airway inflammation in people with eosinophilic asthma

Secondary ID [1]

Nil

Secondary ID [2]

Nil known

Universal Trial Number (UTN)

Trial acronym

PIES (Pneumococcal vaccine In Eosinophilic asthma Study)

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Asthma

Condition category

Condition code

Respiratory

Asthma

Inflammatory and Immune System

Allergies

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Prevenar 13 (Active ingredients: 30.8 mg pneumococcal purified capsular polysaccharides and 32 mg CRM197 protein)
0.5ml to be administered by intramuscular injection
given in 2 doses at monthly intervals

Parallel group to receive Pneumovax 23 (Pneumococcal vaccine polyvalent). It contains a mixture of purified capsular polysaccharides from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae.
Each 0.5 ml dose of vaccine contains 25 mcg of each polysaccharide type dissolved in isotonic saline solution containing 0.25% phenol as preservative.
0.5ml to be administered by intramuscular injection
1 dose given, followed by 1 dose of saline 4 weeks later

Intervention code [1]

Treatment: Other

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Prevenar treatment group will be compared to parallel group who receive Pneumococcal vaccine Pneumovax23

Control group

Active

Outcomes

Primary outcome [1]

Induced sputum eosinophils- Sputum induction will be performed with selection and dispersion of muco-cellular clumps and performance of total and differential cell counts.

Timepoint [1]

Assessed at screening visit, during two treatment visits, at the end of treatment visit, which is 4 weeks after treatment 2, and end of study visit which is 12 months after the first treatment.

Primary outcome [2]

Regulatory T cell numbers and functional responses-
Treg cell numbers and functional responses will be analysed in peripheral blood mononuclear cells through flow cytometry.

Timepoint [2]

Assessed at the two treatment visits and at the end of treatment visit, which is 4 weeks after treatment 2.

Secondary outcome [1]

Asthma symptoms- assessed using the Juniper Asthma Control Questionnaire (ACQ(6))

Timepoint [1]

ACQ(6) will be assessed at screening visit, two treatment visits, end of treatment visit (4 weeks after treatment 2), and end of study visit (12 months after treatment 1)

Secondary outcome [2]

Health status- assessed using the Juniper Asthma Quality of Life
Questionnaire (AQLQ).

Timepoint [2]

AQLQ will be assessed at screening visit, two treatment visits, end of treatment visit (4 weeks after treatment 2), and end of study visit (12 months after treatment 1).

Eligibility

Key inclusion criteria

Symptomatic stable asthma [ACQ(6) > 0.75], confirmed variable airflow obstruction, maintenance therapy

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Forced expiratory volume in 1 second (FEV1) < 40% predicted.. Received pneumococcal vaccination with Pneumovax in the past 12 months, or Prevenar ever. Current smoking (or having quit within 6 months of study entry). Cold or respiratory tract infection within 4 weeks of study entry. Pregnancy, breast feeding, possibility of becoming pregnant (unwilling to use contraception during the treatment phase). Inability to attend study visits. Participation in another investigative drug study within 4 weeks of study entry.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

We will use concealed random allocation. Randomisation is done by a computer generated list. Outcomes will be assessed by staff unaware of treatment allocation.
The person assessing eligibility will not have access to the randomisation information, randomisation will be done over the phone by designated staff members who do not have any participant contact in the study.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The randomisation ratio is 1:1. A computer generated list was created.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 1

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Hypothesis A will be tested using analysis of covariance. A model will be fitted with sputum eosinophils at 52 weeks as the outcome of interest. The predictor variable of interest in the analysis of variance model will be treatment group (Prevenar13 or Pneumovax 23) with baseline level of sputum eosinophils included as a covariate.
Hypothesis B, health status and asthma symptom scores, will also be analysed using analysis of covariance with baseline level included as a covariate.
Baseline characteristics, change scores and end of treatment results will be summarised by treatment group. Continuous outcomes will be analysed using Student’s t test for parametric data and Wilcoxon ranksum tests for nonparametric data. Categorical data will be compared using the Chi square or Fisher’s exact test as appropriate.
Data will be analysed on an intention-to-treat basis using 2-sided tests with p values <0.05 considered statistically significant. The analysis will be repeated on the per protocol population.

Number of study participants for the study:
Alpha: 0.05; Power: 80%; Sample size required is 49 per group, as described below and allowing for dropouts.

ACQ: a clinically important difference is 0.5 units. In a previous study the response within each subject group was normally distributed with standard deviation 0.83. If the true difference in the experimental and control means is 0.5, we will need 44 experimental and 44 control subjects.

FEV1%predicted: In a prior study the response within each subject group was normally distributed with standard deviation 20.8. If the true difference in the experimental and control means is 15.5, we will need to study 29 experimental subjects and 29 control subjects.

Sputum eosinophils: In a previous study the response within each subject group was normally distributed with standard deviation of 16.28%. If the true difference in the experimental and control means is 10%, we will need to study 43 experimental subjects and 43 control subjects.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/06/2016

Actual

1/07/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Hunter Medical Research Institute - New Lambton Heights

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Asthma Australia

Address [1]

PO Box 394
Fortitude Valley QLD 4006

Country [1]

Australia

Primary sponsor type

Other

Name

Hunter Medical Research Institute

Address

1/Kookaburra Circuit, New Lambton Heights NSW 2305

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Human Research Ethics Committee

Ethics committee address [1]

Hunter New England Area Health Service Locked Bag 1, Hunter Region 
Mail Centre, Newcastle NSW 2310

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/04/2016

Approval date [1]

09/05/2016

Ethics approval number [1]

16/04/20/3.01

Ethics committee name [2]

Hunter New England Human Research Ethics Committee

Ethics committee address [2]

Hunter New England Area Health Service Locked Bag 1, Hunter Region Mail Centre, Newcastle NSW 2310

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

20/04/2016

Approval date [2]

09/05/2016

Ethics approval number [2]

16/04/20/3.01

Summary

Brief summary

Asthma is a high impact, chronic inflammatory airway disease where modulation holds the promise of long term clinical benefits. Different types of cells have been involved in asthma such as eosinophils, neutrophils and a mixture of both eosinophils and neutrophils. The main purpose of this study is to see if treatment with conjugated pneumococcal vaccine (Prevenar 13) will help people with eosinophilic asthma. It is hypothesised that Prevenar 13 will attenuate eosinophilic airway inflammation and improve health status.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Peter Gibson

Address

Hunter Medical Research Institute
John Hunter Hospital
Department of Respiratory and Sleep Medicine
Locked Bag 1000,
New Lambton NSW 2305

Country

Australia

Phone

+61240420143

Fax

[email protected]

Contact person for public queries

Name

Catherine Delahunty

Address

Department of Respiratory & Sleep Medicine
Hunter Medical Research Institute
Level 2 West
Locked Bag 1000
New Lambton NSW 2305

Country

Australia

Phone

+61240420135

Fax

+61240420046

[email protected]

Contact person for scientific queries

Name

Peter Gibson

Address

Hunter Medical Research Institute
John Hunter Hospital
Department of Respiratory and Sleep Medicine
Locked Bag 1000,
New Lambton NSW 2305

Country

Australia

Phone

+61240420143

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Basic results	No			366820-(Uploaded-17-12-2020-19-57-22)-Basic results summary.pdf
Plain language summary	No		1. Research Question The aim of this pilot study ... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Neutrophilic asthma features increased airway classical monocytes.	2021	https://dx.doi.org/10.1111/cea.13811

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically