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Trial registered on ANZCTR


Registration number
ACTRN12623000258651p
Ethics application status
Submitted, not yet approved
Date submitted
22/02/2023
Date registered
10/03/2023
Date last updated
10/03/2023
Date data sharing statement initially provided
10/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of MV140 in older adults
Scientific title
Evaluation of the sublingual vaccination MV140 in the prevention of recurrent urinary tract infections in the older adult Australian population - a multi-centre, double-blinded, randomised controlled trial
Secondary ID [1] 309064 0
IIS-2023-027
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent urinary tract infections 329124 0
Condition category
Condition code
Renal and Urogenital 326098 326098 0 0
Other renal and urogenital disorders
Infection 326099 326099 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention arm: MV140
- Dose: 2 puffs (100uL) daily
- Mode of administration: Sublingual
- Duration: 3 months

Compliance will be ensure by participant return of the empty product packaging to the clinical trials pharmacy following the 3-month treatment duration.
Intervention code [1] 325506 0
Prevention
Comparator / control treatment
Control arm: Placebo (sterile water)
- Dose: 2 puffs daily
- Mode of administration: Sublingual
- Duration: 3 months
Control group
Placebo

Outcomes
Primary outcome [1] 333965 0
The number of urinary tract infections detected over 12-months following the completion of a 3-month treatment course of MV140 or Placebo, assessed by positive urine microscopy and cultures and symptoms of urinary tract infection.

Assessment of urine microscopy and culture will be performed by investigators either on-site or via electronic medical records. Urinary tract infection symptoms will be described to participants at trial commencement, and participants are asked to document any such symptoms within their trial diary.
Timepoint [1] 333965 0
3, 6, 9, and 12 months post completion of treatment course
Secondary outcome [1] 418872 0
Any change in the rates of antibiotic usage for UTI following commencement of the trial treatment course, determined by antibiotics commenced for positive urine microscopy and culture or positive urinalysis in conjunction with symptoms of UTI.

Information will be gathered by electronic medical records and participant trial diary.
Timepoint [1] 418872 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [2] 418874 0
To identify whether there is a change in bacterial profile on urine microscopy and culture following commencement of trial therapy.

Information will be gathered by electronic medical records.
Timepoint [2] 418874 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [3] 418875 0
The number of urinary tract infections detected following the commencement trial therapy, assessed by positive urine microscopy and cultures and symptoms of urinary tract infection.

Assessment of urine microscopy and culture will be performed by investigators either on-site or via electronic medical records. Urinary tract infection symptoms will be described to participants at trial commencement, and participants are asked to document any such symptoms within their trial diary.
Timepoint [3] 418875 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [4] 418876 0
Proportion of patients that remain UTI free in the 2 study arms in the 12-month period following completion trial therapy, assessed by positive urine microscopy and cultures and symptoms of urinary tract infection.

Assessment of urine microscopy and culture will be performed by investigators either on-site or via electronic medical records. Urinary tract infection symptoms will be described to participants at trial commencement, and participants are asked to document any such symptoms within their trial diary.
Timepoint [4] 418876 0
3, 6, 9, and 12 months post treatment completion
Secondary outcome [5] 418877 0
Patient reported outcomes data on quality of life before and 12-months after completion of MV140, assessed using the validated quality of life questionnaire SF-36
Timepoint [5] 418877 0
Trial commencement and 15-months post first-dose of trial therapy
Secondary outcome [6] 418878 0
The time taken (days) to first urinary tract infection detected following commencement of trial therapy into MV140 or Placebo treatment arms, assessed by positive urine microscopy and culture and symptoms of urinary tract infection.

Assessment of urine microscopy and culture will be performed by investigators either on-site or via electronic medical records. Urinary tract infection symptoms will be described to participants at trial commencement, and participants are asked to document any such symptoms within their trial diary.
Timepoint [6] 418878 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [7] 418879 0
The number of presentations to a General Practitioner for UTI following commencement of trial therapy assessed by positive urine microscopy and culture and symptoms of urinary tract infection.

Information will be gathered by data linkage to medical records and patient trial diary.
Timepoint [7] 418879 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [8] 418880 0
Number of presentations to Emergency for UTI following commencement of trial therapy, assessed by positive urine microscopy and culture and symptoms consistent with UTI.

Information will be sourced by electronic medical records and patient trial diary.
Timepoint [8] 418880 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [9] 418881 0
Number of hospitalisations due to UTI following commencement of trial therapy, assessed by positive urine microscopy and culture and symptoms consistent with UTI.

Information will be sourced by electronic medical records and patient trial diary.
Timepoint [9] 418881 0
3, 6, 9, 12, and 15 months post commencement of trial therapy
Secondary outcome [10] 418882 0
Side effects: type, severity, and duration

Known adverse effects include: Sore throat, oral thrush, and nausea.

Side effects will be assessed during 3-monthly consultations with participants by study investigators with clinical examination as required, or if participants are to contact study investigators due to a possible adverse effect.
Timepoint [10] 418882 0
3, 6, 9, 12, and 15 months post commencement of trial therapy

Eligibility
Key inclusion criteria
• People aged greater than or equal to 65-years of any gender
• Recurrent UTI (defined as 3 or more UTIs within the last 12 months)
• Competence to consent to participate in trial and comply with study requirements
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of bladder tumours
• Diagnosed bladder fistula disease
• Currently receiving immunotherapy for another condition
• Any immunological disease requiring active treatment
• Known intolerance/allergy to MV140 or ingredients it contains
• Known bladder stones
• Long-term urinary catheter dependence (IDC/SPC)
• Unable to provide informed consent or meet study requirements

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed to investigators and participants.

A trial manager is in place to provide allocation of participants into treatment arms using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomised allocation will be used to allow separate randomisation of men and women to prevent gender being a confounding factor.

Randomisation schema will be generated by the study biostatistician using STATA V17 software.
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
Study candidates will be identified and recruited from across Northern Sydney Local Health District inpatients and outpatient clinics via referral to the investigation team.

An introductory consult will take place to review inclusion and exclusion criteria, explain the study aims, treatment, and expectations for the candidate. A PISCF will be provided to the patient and they will be recontacted within 7-14 days to confirm consent.

Subsequently, an initial study consult will take place during which a urine MCS, uroflowmetry, and post-void residual bladder scan performed, and study steps involved for the patient explained. Participants will be randomised at this stage and provided a de-identified unique trial number. Each enrolled participant will have a history and examination specific to urinary tract infections undertaken, including review of electronic medical records to ascertain pertinent information to the study: Number of UTIs, urine microscopy and culture results, emergency department presentations, hospital admissions, courses of antibiotics, and alternative treatments for UTI. Participants will be provided a ‘study diary’, and its use will be explained.

Participants will undergo computer randomisation using STATA V17 software performed by the study biostatistician into 1 of 2 treatment arms MV140 vs. Placebo. Participants will undergo a 3-month treatment course.

Participants will be contacted at the conclusion of treatment and every 3-months thereafter via telephone consult from the investigator for 12-months. During each follow-up consult, the study diary will be reviewed to ascertain volume of urinary tract infections, treatments, and possible side effects.

The participant’s involvement in the study will conclude at the 12-month follow-up consultation.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample Size Estimation

Sample size analysis indicated that to detect a medium effect of 0.5 standard deviations difference in UT infections between treatment and control groups at a .05 level of significance, 0.80 power, and adjusting for a 10% dropout rate, a total of 150 patients (75 per group) must be recruited and included in the study.

Population to be analysed

Participants of any gender aged older than 65-years will be included within the study. Participants will be recruited from inpatients and outpatients across the NSLHD.

Statistical Analysis Plan

The data will be presented as mean, standard deviation (symmetric normal data), median, inter-quartile range (skewed data or ordinal data), proportions, risk ratios, and hazard ratios with 95% confidence intervals. The primary outcome of interest is the difference in the volume of UTI between treatment (MV140) and placebo groups after 12 months of follow-up. It will be tested using the Mann-Whitney U test. A Poisson regression model will be used to estimate and compare the UTI incidence rate between treatment and placebo groups. The UTI-free rate between two groups will be compared using Chi-square/Fisher’s exact test.
The number needed to treat (NNT) was calculated based on the number of patients to be treated to prevent one case of UTI during the study and was computed as the reciprocal of the absolute risk reduction (ARR) which is defined as the proportion of control events minus the proportion of treatment events.

The time to first UTI will be assessed using the Kaplan-Meier estimator. The significance of the difference in time to the first UTI between treatment and control groups will be tested using log-rank tests. The associated hazard ratio (event of first UTI) and their 95% confidence intervals will be estimated by Cox’s proportional hazards regression model. The assumption of the proportionality of hazards will be tested using the Schoenfeld residuals test. Robust standard errors will be used if the Schoenfeld residuals test indicates a violation of the proportionality assumption in Cox’s regression model. Rates of presentation of GP for UTI, presentations to Emergency for, UTI, and hospitalisation due to UTI will be compared using Chi-square / Fisher’s exact test.

All the statistical tests will be performed at a .05 level (0 < .05) of significance. All the statistical analyses will be performed in STATA V17.0.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
Date of last participant enrolment
Anticipated
3/07/2023
Actual
Date of last data collection
Anticipated
3/10/2024
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24116 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 24117 0
Northern Beaches Hospital - Frenchs Forest
Recruitment hospital [3] 24118 0
Ryde Hospital - Eastwood
Recruitment hospital [4] 24119 0
Hornsby Ku-ring-gai Hospital - Hornsby
Recruitment postcode(s) [1] 39624 0
2065 - St Leonards
Recruitment postcode(s) [2] 39625 0
2086 - Frenchs Forest
Recruitment postcode(s) [3] 39626 0
2122 - Eastwood
Recruitment postcode(s) [4] 39627 0
2077 - Hornsby

Funding & Sponsors
Funding source category [1] 313269 0
Commercial sector/Industry
Name [1] 313269 0
Australasian Medical & Scientific Ltd.
Country [1] 313269 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Australasian Medical & Scientific Ltd.
Address
2 McCabe Pl, Chatswood NSW 2067
Country
Australia
Secondary sponsor category [1] 315007 0
None
Name [1] 315007 0
Address [1] 315007 0
Country [1] 315007 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312500 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 312500 0
Ethics committee country [1] 312500 0
Australia
Date submitted for ethics approval [1] 312500 0
22/02/2023
Approval date [1] 312500 0
Ethics approval number [1] 312500 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124882 0
Dr James Kovacic
Address 124882 0
Department of Urology, Royal North Shore Hospital, Reserve Rd, St Leonards, 2065, NSW
Country 124882 0
Australia
Phone 124882 0
+61 411359053
Fax 124882 0
Email 124882 0
james.kovacic@health.nsw.gov.au
Contact person for public queries
Name 124883 0
James Kovacic
Address 124883 0
Department of Urology, Royal North Shore Hospital, Reserve Rd, St Leonards, 2065, NSW
Country 124883 0
Australia
Phone 124883 0
+61 411359053
Fax 124883 0
Email 124883 0
james.kovacic@health.nsw.gov.au
Contact person for scientific queries
Name 124884 0
James Kovacic
Address 124884 0
Department of Urology, Royal North Shore Hospital, Reserve Rd, St Leonards, 2065, NSW
Country 124884 0
Australia
Phone 124884 0
+61 411359053
Fax 124884 0
Email 124884 0
james.kovacic@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To minimise risk of confidentiality breach and to ensure data is presented following analysis in a contextualised manner in an effort to avoid misconstrued interpretation.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18419Study protocol    The investigators are intending to publish the stu... [More Details]
18420Statistical analysis plan    The statistical analysis plan will be documented w... [More Details]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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