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Trial registered on ANZCTR


Registration number
ACTRN12623000861651
Ethics application status
Approved
Date submitted
30/06/2023
Date registered
11/08/2023
Date last updated
11/08/2023
Date data sharing statement initially provided
11/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Clinical Trial to see if a herbal medicine, Urox can prevent the recurrence of a urinary tract infections (UTIs) and cystitis.
Scientific title
A phase IIb Double-Blind, Placebo-controlled Randomised Clinical Trial assessing the efficacy of Urox for the prevention of recurrent urinary tract infections (UTIs) and cystitis.
Secondary ID [1] 309952 0
None
Universal Trial Number (UTN)
Trial acronym
URELIEF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Urinary tract infections 330435 0
Recurrent Cystitis 330436 0
Condition category
Condition code
Renal and Urogenital 327280 327280 0 0
Other renal and urogenital disorders
Infection 327751 327751 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
UROX® is a herbal therapeutic good, a proprietary combination of three herbal extracts, listed with the Australian Therapeutics Goods Administration, AUSTL400655. UROX contains Horsetail 150mg, Lindera 150mg and Crateva 120mg in one capsule.

Dose: 2 capsules a day in the morning for 6 months
Compliance: 4 weekly follow up (online) visits will be conducted to assess number of capsules left for each participant for the 6 months. Blood tests will be conducted at screening and at 6 months, urine tests will be conducted at each acute episode from a participant.
Intervention code [1] 326370 0
Prevention
Comparator / control treatment
Placebo - The placebo contains Calcium hydrogen phosphate and silica dioxide in a colour matched vegetarian capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 335154 0
Incidence of UTIs, and/or cystitis at 6 months. This is a composite primary outcome as the acute episode won't be assessed for cystitis although the participant maybe experiencing it.

At each acute episode, the participant is required to take a urine sample to be tested. They will then receive an automatic patient reported questionnaire (Urinary Tract Infection Symptom Assessment - UTISA) via text to complete for the next 7 days.
Timepoint [1] 335154 0
From baseline to 6 months (24 weeks)
Primary outcome [2] 335155 0
Severity of UTI symptoms via UTI symptom assessment (UTISA)
Timepoint [2] 335155 0
From baseline to 6 months (24 weeks)
Secondary outcome [1] 423294 0
Time to recurrence, i.e., time interval between UTI episodes. This will be assessed by the number of reported acute UTI episodes the patient reports which is recorded on REDCap and documented by the research assistant with the distance between episodes documented for analysis.
Timepoint [1] 423294 0
From baseline to 6 months. Follow ups occurring monthly while on intervention
Secondary outcome [2] 423295 0
Duration of UTI symptoms. This will be assessed by the patient-reported outcome measure (UTISA) which will be automatically sent to the participant upon reporting and acute episode. The duration of the UTI will be measured by this questionnaire and recorded.
Timepoint [2] 423295 0
From baseline to 6 months. Follow ups occurring monthly while on intervention
Secondary outcome [3] 423296 0
Number of days of antibiotic use for cystitis and/or UTIs. This will be assessed by a phone call by the research assistant on day 7 after an acute episode.
Timepoint [3] 423296 0
From baseline to 6 months. Follow ups occurring monthly while on intervention
Secondary outcome [4] 423297 0
Number of days of hospitalisation due to UTIs/cystitis. This will be assessed by a phone call by the research assistant on day 7 after an acute episode.
Timepoint [4] 423297 0
From baseline to 6 months. Follow ups occurring monthly while on intervention
Secondary outcome [5] 423298 0
Impairment via the Overactive Bladder questionnaire (OABq SF)
Timepoint [5] 423298 0
From baseline to 12 months. Follow ups occurring monthly while on intervention
Secondary outcome [6] 423299 0
Burden of UTI via Recurrent UTI Impact Questionnaire (RUTIIQ)
Timepoint [6] 423299 0
From baseline to 12 months. Follow ups occurring monthly while on intervention
Secondary outcome [7] 423300 0
Satisfaction via the Benefit, Satisfaction, Willingness (BSW)
Timepoint [7] 423300 0
From baseline to 12 months. Follow ups occurring monthly while on intervention
Secondary outcome [8] 423301 0
Quality of life via the SF-36
Timepoint [8] 423301 0
From baseline to 12 months. Follow ups occurring monthly while on intervention
Secondary outcome [9] 423302 0
Safety via adverse events via follow up visit questions on case report form.
Timepoint [9] 423302 0
From baseline to 6 months. Follow ups occurring monthly while on intervention
Secondary outcome [10] 423303 0
Safety via liver enzymes via blood samples
Timepoint [10] 423303 0
From baseline to 6 months. Follow ups occurring monthly while on intervention.
Secondary outcome [11] 423304 0
Safety via kidney function via blood samples
Timepoint [11] 423304 0
From baseline to 6 months. Follow ups occurring monthly while on intervention.
Secondary outcome [12] 423305 0
12 months incidence of UTIs/cystitis (participant self-report)
Timepoint [12] 423305 0
Baseline and 12 months
Secondary outcome [13] 423306 0
The number of times they had to commence of prophylaxis medication via patient report at the follow up visit.
Timepoint [13] 423306 0
Baseline, 12 months

Eligibility
Key inclusion criteria
History of recurrent UTI or cystitis (self-reported previous medical diagnosis) defined as at least two episodes of UTI and/or acute cystitis in the last 6 months and/or at least 3 episodes of UTI and/or acute cystitis in the last 12 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Those who fulfil the following exclusion criteria cannot be considered for participation:

Medical History
1. Symptoms of acute systemic inflammatory response, infection, or fever (sweats/chills) at screening
2. History of physical urinary tract abnormalities
3. History of an unmanaged and/or poorly managed chronic disease
4. Recent (within previous 6 months) history of kidney stones (renal calculi)
5. History of chronic kidney disease or kidney dysfunction
6. History of chronic kidney infection (chronic pyelonephritis)
7. History of bladder or kidney cancer or other significant urinary co-morbidity
8. Presence of an indwelling or suprapubic catheter, or current use of in/out catheters to aid urination
9. Known allergy to any of the ingredients in the IMP

Medications
1. Current administration of antibiotics
2. Current administration of natural prophylaxis such as cranberry or d-mannose or other natural supplements or herbal medicine for urinary tract infections/cystitis treatment or associated symptoms. These supplements may be ceased for 28 days to allow for trial inclusion at the participant’s discretion.
3. Concurrent administration of any supplement containing any ingredient of the IMP
4. Current treatment for cancer except hormone deprivation therapy or hormone blocking medication
5. Current use of anti-diabetic drugs e.g. metformin, insulin
6. Current use of lithium

Pathology abnormalities
1. Liver enzymes if greater than 1.5 x ULN
2. eGFR if below 70 on screening pathology
3. Urine pathology indicative of current UTI/infective cystitis
4. TSH > 5 (males only)

Other
1. Pregnant or breast-feeding women
2. Unwilling to use effective contraception during the trial (those of child-bearing capacity only)

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)
The supplier will provide the medication in containers already labelled to ensure concealment. One person in from the funder will know the allocation to ensure all investigators for the trial do not have access to the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation sequence will be a computer-generated random number based on block randomisation with varying block length ranging from 6 to 10 with a stratum for participant’s sex. The randomisation sequence will be generated via the online platform www.sealedenvelope.com.
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
Statistical methods / analysis
All data will be analysed via SPSS 28.0, or other statistical program. The analyses will be conducted on an intention-to-treat analysis, followed by a subsequent per-protocol analysis. Missing data will be imputed using the Markov chain Monte Carlo multiple imputation method in SPSS.

The primary outcome is a combined outcome at 6 months. Severity of UTI symptoms will be analysed using analysis of co-variance (ANCOVA), which models the posttreatment outcome as a function of treatment group (classified factor), and compliance (linear covariate). The incidence of UTIs will be compared between groups using Chi2 tests, or non-parametric tests for categorical data.
Efficacy estimates will be reported as group differences with 95% confidence intervals, and effect sizes. A significance level of 5% will be applied with no correction for the primary outcome.

Secondary outcomes will be analysed with equivalent methods. Responders will be defined as participants who had greater than 1 acute cystitis and/or UTI episode in 6 months and compared via Chi2 tests. Associations between self-report and objective outcomes will be analysed using correlational, and regression techniques. Time to recurrence will be analysed using Kaplan Meyer survival estimates.
Interim analysis

No interim blind analysis has been planned.

IMP compliance data
The IMP compliance data will be collated over the trial period and presented as absolute and relative frequencies. The compliance data will be compared between groups via independent t-tests, or non-parametric tests as required. Compliance data will be used as a covariate for the analysis of the primary and secondary outcomes.

Adverse Event data
The adverse event data will be reported descriptively via absolute and relative frequencies, presented separately for system organ classes, and severity.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/08/2023
Actual
Date of last participant enrolment
Anticipated
30/08/2024
Actual
Date of last data collection
Anticipated
30/08/2025
Actual
Sample size
Target
202
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 314129 0
Commercial sector/Industry
Name [1] 314129 0
Seipel Group
Country [1] 314129 0
Australia
Funding source category [2] 314130 0
Charities/Societies/Foundations
Name [2] 314130 0
Jacka Foundation
Country [2] 314130 0
Australia
Primary sponsor type
University
Name
Southern Cross University
Address
1 Military Road, Lismore NSW 2480
Country
Australia
Secondary sponsor category [1] 316047 0
University
Name [1] 316047 0
National Centre for Naturopathic Medicine
Address [1] 316047 0

Southern Cross University
1 Military Road
Lismore NSW 2480
Country [1] 316047 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313265 0
Southern Cross University HREC
Ethics committee address [1] 313265 0
Ethics committee country [1] 313265 0
Australia
Date submitted for ethics approval [1] 313265 0
05/06/2023
Approval date [1] 313265 0
02/08/2023
Ethics approval number [1] 313265 0
2023/151

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

Contacts
Principal investigator
Name 127534 0
Dr Janet Schloss
Address 127534 0
Southern Cross University
National Centre for Naturopathic Medicine
1 Military Road, Lismore NSW 2480
Country 127534 0
Australia
Phone 127534 0
+61 436 101 306
Fax 127534 0
Email 127534 0
[email protected]
Contact person for public queries
Name 127535 0
Janet Schloss
Address 127535 0
Southern Cross University
National Centre for Naturopathic Medicine
1 Military Road, Lismore NSW 2480
Country 127535 0
Australia
Phone 127535 0
+61 436 101 306
Fax 127535 0
Email 127535 0
[email protected]
Contact person for scientific queries
Name 127536 0
Janet Schloss
Address 127536 0
Southern Cross University
National Centre for Naturopathic Medicine
1 Military Road, Lismore NSW 2480
Country 127536 0
Australia
Phone 127536 0
+61 436 101 306
Fax 127536 0
Email 127536 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
No individual data will be made publicly available. All data will be presented as cumulative results.


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.