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Trial registered on ANZCTR


Registration number
ACTRN12618001171202
Ethics application status
Approved
Date submitted
4/07/2018
Date registered
16/07/2018
Date last updated
23/09/2021
Date data sharing statement initially provided
17/07/2019
Date results information initially provided
23/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Bactek­O Sublingual Vaccine Treatment in Bronchiectasis - A Pilot Study
Scientific title
Changes in sputum procalcitonin with Bactek -O sublingual vaccine treatment in adult patients with non­-cystic fibrosis  bronchiectasis: A pilot study
Secondary ID [1] 295360 0
HRC 18/113
Universal Trial Number (UTN)
U1111-1216-7308
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-cystic fibrosis bronchiectasis 308582 0
Condition category
Condition code
Respiratory 307536 307536 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single centre, double-blinded, randomised, placebo-controlled study in patients with non-cystic fibrosis bronchiectasis. Patients aged over 18 years with non-cystic fibrosis bronchiectasis diagnosed by high-resolution CT scan.

Bactek-O is a commercially available polyvalent bacterial preparation (Immunotek Laboratories, Madrid, Spain). It is administered in liquid form as a spray, sublingually. It contains different species of inactivated bacteria that are frequently present in the respiratory tract: Streptococcus pyogenes (15%), Moraxella catarrhalis (15%), Haemophilus influenzae (35%), Streptococcus pneumoniae (35%). The other excipients are glycerol, pineapple essence to improve taste, sodium chloride and water for injection

Bactek-O vaccine and a placebo will be identically packaged and delivered sublingually. Eligible subjects will be randomised to Bactek-O vaccine or placebo with the following regime: day 1, one sublingual spray and thereafter, up to day 180, two sublingual sprays daily. The total duration of treatment is therefore 6 months. The dose is 2 x 100 µL sprays. In terms of active ingredients, there is 10^9 bacteria/mL so each spray would have 10^8 b/mL.

Adherence will be monitored and measured by keeping and reviewing the bottles both through visual inspection and weight assessment. Patient's adherence with the proper use of the study drug or placebo will be assessed at visits 3 and 4, and patients will be reminded to bring all study medication pack(s) (used or unused) and completed diaries to these visits
Intervention code [1] 301683 0
Treatment: Drugs
Comparator / control treatment
Placebo containing glycerol, pineapple essence to improve taste, sodium chloride and water for injection
Control group
Placebo

Outcomes
Primary outcome [1] 306516 0
Sputum procalcitonin
Timepoint [1] 306516 0
Comparison between baseline and 6 months
Secondary outcome [1] 348735 0
Bactek-O vaccine safety
- safety will be measured by regularly assessing for adverse events or side effects. This will be performed at study visits (week 0, 4, 12 and 24). There will also be phone calls on week 1, 3, 6, 10, 16 and 22.
- Patients will also be requested to documents any symptoms or concerns in their diary cards provided throughout the study.
Timepoint [1] 348735 0
Baseline and 6 months (see above for further details)
Secondary outcome [2] 349151 0
Health-related Quality of Life in bronchiectasis patients
• St. George’s Respiratory Questionnaire (SGRQ)
• Bronchiectasis Health Questionnaire (BHQ)
• The Leicester Cough Questionnaire (LCQ)
Timepoint [2] 349151 0
Baseline and 6 months
Secondary outcome [3] 349152 0
Lung function (FEV1, FVC) which will be measured using spirometry.
Timepoint [3] 349152 0
Baseline and 6 months
Secondary outcome [4] 349153 0
Pulmonary exacerbations - this is defined in relation to the recent ERS consensus definition. This requires "a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is require".
- This will be assessed during study visits and phone calls. The diary card also contains all of these components which will allow us to determine the suitability of antibiotic prescription in the community.
- Both number of exacerbations and time to first exacerbation will be assessed.
Timepoint [4] 349153 0
Baseline and 6 months
Secondary outcome [5] 349154 0
Effect on lung and nasopharyngeal microbiome
• Microbiome analysis from nasopharyngeal swab and sputum at baseline and 6 months
• Ecological network analyses to look at bacterial co-occurrence and potential deterrence within the airway microbiome
Timepoint [5] 349154 0
Baseline and 6 months
Secondary outcome [6] 349155 0
Sputum and plasma cytokines – interferon, IL-4 IL-5, IL-6, IL-8, IL-10, TNF-a
Timepoint [6] 349155 0
Baseline and 6 months
Secondary outcome [7] 349156 0
Systemic inflammation using plasma CRP and blood neutrophil counts
Timepoint [7] 349156 0
Baseline and 6 months
Secondary outcome [8] 349430 0
Batek-O tolerance and adherence
- these will be assessed by weighing medication bottles and asking patients to return empty bottles. They will also document daily administration in their diary cards.
Timepoint [8] 349430 0
Diary cards will be reviewed during study visits (week 4, 8, 12 and 24) as medication will be weighed at study visits at week 12 and 24.
Secondary outcome [9] 372737 0
Impact on co-existing sinus disease using SNOT-22 questionnaire
Timepoint [9] 372737 0
Baseline and at 6 months
Secondary outcome [10] 401281 0
Sputum high-sensitivity CRP
Timepoint [10] 401281 0
Baseline and at 6 months (end of study)
Secondary outcome [11] 401282 0
Sputum neutrophil elastase
Timepoint [11] 401282 0
Baseline and at 6 months (end of study)

Eligibility
Key inclusion criteria
• Aged 18 years or over.
• Able to provide written informed consent.
• Able to provide spontaneous sputum sample at visit 2 (week 0).
• High-resolution CT scan (HRCT) diagnosis of bronchiectasis; CT scan performed within the past 5 years
• Clinically stable during baseline period, which is 4 weeks prior to randomisation (as defined by the absence of clinical worsening beyond normal daily variation, with no need for increasing habitual medications or taking antibiotics or prednisone and stable spirometry).
• History of at least one pulmonary exacerbation requiring antibiotic treatment in the past 12 months. Patients with asthma and COPD will be included if the primary diagnosis is bronchiectasis.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Oral or intravenous antibiotic treatment (including macrolides) within 4 weeks prior to commencing study drug.
• Patients taking continuous oral corticosteroids (> 6 weeks) or immunosuppressive agents (e.g. azathioprine, methotrexate, cyclophosphamide).
• Bronchiectasis exacerbation or respiratory infection requiring oral or intravenous antibiotic or steroid treatment within 4 weeks prior to commencing study drug.
• Patients with a history of non-adherence with medications.
• Patients with significant medical conditions other than bronchiectasis.
o A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient’s ability to participate in the study.
• Patients with cystic fibrosis.
• Patients with hypo-gammaglobulinaemia.
• Patients with primary ciliary dyskinesia.
• Patients with allergic bronchopulmonary aspergillosis (total IgE >420 IU/mL and aspergillus specific IgE level of +3 or +4, and proximal bronchiectasis on HRCT).
• Patients with evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is greater than or equal to 20% within 2 years judged by the treating physician (patients with basal cell carcinoma and squamous cell carcinoma are allowed). Patients who have undergone resection, radiation therapy or chemotherapy within 6 months prior to the first dose of the study drug or the expectation that such treatment will be required at any time during the study will also be excluded.
• Pregnant or lactating women.
• Participation in a separate clinical or device trial within 4 weeks prior to screening.
• Allergy to any of the components of Bactek-O
• Patients with chronic bacterial infection of Pseudomonas aeriginosa. This is defined by positive culture from standard microbiology from the lower airways of the same Pseudomonas aeriginosa on two or more occasions at least three months apart over one year in stable state.

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)
Patients will be randomly assigned to receive either Bactek-O or placebo in a 1:1 ratio according to centre-stratified block randomisation with random block sizes. The exact distribution of the block sizes will only be known to statistician external to the study until unblinding to promote concealment. Randomisation will take place at the second visit, immediately prior treatment commencement. Bottles will be labelled with a number according to the randomisation schedule. The bottles will be dispensed in consecutive order as the participants are recruited. The number on the first dispensed bottle will become the participant identifier.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomly assigned to receive either Bactek-O or placebo by computer generation technique
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Associate Professor Alain Vandal (Senior Biostatistician) was involved in the sample size calculation and will perform future statistical analyses for this study. A sample size of 40 participants gives a reasonable estimate of variance in a pilot study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/09/2018
Actual
3/12/2018
Date of last participant enrolment
Anticipated
26/08/2019
Actual
24/09/2019
Date of last data collection
Anticipated
23/03/2020
Actual
10/03/2020
Sample size
Target
40
Accrual to date
Final
46
Recruitment outside Australia
Country [1] 10594 0
New Zealand
State/province [1] 10594 0
Auckland

Funding & Sponsors
Funding source category [1] 299954 0
Government body
Name [1] 299954 0
Health Research Council of New Zealand
Country [1] 299954 0
New Zealand
Funding source category [2] 299955 0
Government body
Name [2] 299955 0
Counties Manukau-DHB
Country [2] 299955 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of New Zealand
Address
Level 3, 110 Stanley St
Grafton
Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 299334 0
Government body
Name [1] 299334 0
Counties Manukau DHB
Address [1] 299334 0
100 Hospital Road
Otahuhu
2025
Country [1] 299334 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300818 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 300818 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 300818 0
New Zealand
Date submitted for ethics approval [1] 300818 0
12/07/2018
Approval date [1] 300818 0
24/07/2018
Ethics approval number [1] 300818 0
18/CEN/127

Summary
Brief summary
Bronchiectasis is a troublesome disease characterised by productive cough, airway inflammation, and repeated respiratory infections. There are currently no specific treatments licensed for use in bronchiectasis worldwide. Oral bacterial vaccines have been shown to regulate the immune system and enhance the killing of important respiratory bacteria.

This is a single center, double-blinded randomised, placebo-controlled study in adult patients with non-cystic fibrosis bronchiectasis. The main aim of this study is to assess whether Bactek-O (a sublingual bacterial vaccine) can reduce inflammation in the lungs. We will also assess for similar changes in the bloodstream and whether the types of bacteria present in the lungs change following use of Bactek-O.

This pilot study will provide important information for the development of a larger study to assess whether Bactek-O treatment can prevent flare-ups (exacerbations) in patients with bronchiectasis.

Participants will attend 5 study visits (one of which is a screening visit) over this 6 month study where they will have their health-assessed (vital signs, lung function, sputum, nasal swabs and blood samples taken), complete questionnaires and study diaries.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84914 0
Dr William Good
Address 84914 0
Respiratory Department
Counties Manukau DHB
100 Hospital Road
Otahuhu
2025
Country 84914 0
New Zealand
Phone 84914 0
+64 2102960075
Fax 84914 0
Email 84914 0
William.Good@middlemore.co.nz
Contact person for public queries
Name 84915 0
Dr William Good
Address 84915 0
Respiratory Department
Counties Manukau DHB
100 Hospital Road
Otahuhu
2025
Country 84915 0
New Zealand
Phone 84915 0
+64 2102960075
Fax 84915 0
Email 84915 0
William.Good@middlemore.co.nz
Contact person for scientific queries
Name 84916 0
Dr William Good
Address 84916 0
Respiratory Department
Counties Manukau DHB
100 Hospital Road
Otahuhu
2025
Country 84916 0
New Zealand
Phone 84916 0
+64 2102960075
Fax 84916 0
Email 84916 0
William.Good@middlemore.co.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only, after de-identification.
When will data be available (start and end dates)?
Ending 5 years following main results publication
Available to whom?
Case by case at the discretion of the investigators
Available for what types of analyses?
Meta-analyses
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator
- Dr William Good = William.Good@middlemore.co.nz


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.