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Trial registered on ANZCTR


Registration number
ACTRN12617000585325p
Ethics application status
Submitted, not yet approved
Date submitted
19/04/2017
Date registered
26/04/2017
Date last updated
18/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing Hiprex tablets and Nitrofurantoin in women with recurrent urine infections
Scientific title
Methenamine Hippurate (Hiprex) versus Nitrofurantoin for recurrent lower urinary tract infection in women: An open-label non-inferiority multi-centre randomised controlled trial
Secondary ID [1] 291729 0
None
Universal Trial Number (UTN)
U1111-1195-6864
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
recurrent urinary tract infection 302918 0
Condition category
Condition code
Renal and Urogenital 302401 302401 0 0
Other renal and urogenital disorders
Infection 302440 302440 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Methenamine Hippurate tablets, 1 gram twice a day for 6 months
Arm 2: Nitrofurantoin capsules 100 mg once a day for 6 months

As the drugs are all supplied to patients by PBS scripts and they may purchase medications from any pharmacy we won't be able to check their adherence by any means except for patient reported adherence and doctor-patient trust
Intervention code [1] 297836 0
Treatment: Drugs
Comparator / control treatment
Comparing between Methenamine Hippurate and Nitrofurantoin
Control group
Active

Outcomes
Primary outcome [1] 301812 0
Recurrence of UTI in the 6 months duration of trial

If a participant reported symptoms suggesting UTI (See below for Diagnosis of UTI), a clean mid-stream urine sample for culture and sensitivity will be collected. If UTI was diagnosed based on the criteria described below, then the appropriate antibiotic therapy will be commenced with a follow up sample urine to confirm complete treatment of the UTI. A UTI during the trial phase will not lead to exclusion from the study. Patients will continue the treatment to which they were assigned in the beginning of the trial.

We will collect midstream urine samples with patients not voiding for at least 3 hours earlier and after washing the genital area with a sterile water wipe. We define diagnosis of UTI based on 1000 or more colony- forming units (CFU) in 1 ml of clean voided midstream urine, and at least two of the following lower urinary tract symptoms (LUTS): dysuria, frequency, urgency, suprapubic pain, nocturia and hematuria.
Timepoint [1] 301812 0
anytime during the 6 months
Secondary outcome [1] 333937 0
Number of UTI

The number of times a patient experiences UTI

If a participant reported symptoms suggesting UTI (See below for Diagnosis of UTI), a clean mid-stream urine sample for culture and sensitivity will be collected. If UTI was diagnosed based on the criteria described below, then the appropriate antibiotic therapy will be commenced with a follow up sample urine to confirm complete treatment of the UTI. A UTI during the trial phase will not lead to exclusion from the study. Patients will continue the treatment to which they were assigned in the beginning of the trial.

We will collect midstream urine samples with patients not voiding for at least 3 hours earlier and after washing the genital area with a sterile water wipe. We define diagnosis of UTI based on 1000 or more colony- forming units (CFU) in 1 ml of clean voided midstream urine, and at least two of the following lower urinary tract symptoms (LUTS): dysuria, frequency, urgency, suprapubic pain, nocturia and hematuria.
Timepoint [1] 333937 0
6 months
Secondary outcome [2] 334038 0
Time to first UTI

Measured in days since the commencement of the trial

If a participant reported symptoms suggesting UTI (See below for Diagnosis of UTI), a clean mid-stream urine sample for culture and sensitivity will be collected. If UTI was diagnosed based on the criteria described below, then the appropriate antibiotic therapy will be commenced with a follow up sample urine to confirm complete treatment of the UTI. A UTI during the trial phase will not lead to exclusion from the study. Patients will continue the treatment to which they were assigned in the beginning of the trial.

We will collect midstream urine samples with patients not voiding for at least 3 hours earlier and after washing the genital area with a sterile water wipe. We define diagnosis of UTI based on 1000 or more colony- forming units (CFU) in 1 ml of clean voided midstream urine, and at least two of the following lower urinary tract symptoms (LUTS): dysuria, frequency, urgency, suprapubic pain, nocturia and hematuria.
Timepoint [2] 334038 0
6 months
Secondary outcome [3] 334039 0
Adverse events and side effects

Any adverse event and side effects reported by patients will be documented and reported

Methenamine Hippurate:
Nausea, Upset stomach, Painful urination, Rash, Inflammation of the mouth

Nitrofurantoin:
Nausea, Vomiting, Diarrhoea, Headache and dizziness, Drowsiness, Feeling week
Timepoint [3] 334039 0
6 months
Secondary outcome [4] 334040 0
Cost of treatment

The cost of each medication is available as per the pharmaceutical benefits scheme (PBS)
www.pbs.gov.au
Timepoint [4] 334040 0
6 months

Eligibility
Key inclusion criteria
- 18 years old and above
- Have the capacity to give voluntary and informed consent
- Recurrent UTI with documented 2 or more infections in the last 6 months or 3 or more in the last 12 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
*Contraindication to Hiprex: Severe renal or hepatic insufficiency, know allergy. Current use of sulphonamides e.g. sulfamethizole or sulfathiazole
*Contraindication to nitrofurantoin: Known allergy to Nitrofurantoin, G6PD enzyme deficiency, active hepatitis, Jaundice, interstitial pneumonitis, pulmonary fibrosis, severe renal insufficiency
*Previously tried and failed Hiprex prophylaxis
*Pregnancy/Breastfeeding
*Underlying renal disease e.g. renal transplant, vesicoureteric reflux
*Urethral disorders e.g. stricture, diverticulum
*Bladder outlet obstruction e.g. stage 3 or 4 cystocele
*Presence of fistula e.g. vesicovaginal or rectovaginal
*Urolithiasis
*Currently on prophylaxis or recent history of prophylaxis in last 3 months
*Permanent urinary indwelling catheter
*Poorly controlled diabetes mellitus
*Immunosuppressive treatments

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 involves contacting the staff in the administration office who will access the block randomisation tables and allocate the participants to either arm of the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be in order of block randomisation using a block random sequence generator. We will use randomisation in permuted blocks to achieve balance in each arm.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Multicentre study: 3 centres are participating in this trial.
- Mercy Hospital for Women
163 Studley Road, Heidelberg VIC 3084 Australia

- Monash Medical Centre and Austin Hospital
246 Clayton Rd, Clayton VIC 3168 Australia

- Austin Hospital
145 Studley Road, Heidelberg VIC 3084 Australia
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
We calculated the sample size for this non-inferiority study using an estimate of 60% success for the nitrofurantoin group and a 15% non-inferiority limit. With 5% alpha and 80% power, we therefore require 264 patients (132 in each group).

The intention-to-treat (ITT) analysis approach, supported by the per-protocol approach, will be adopted to make inference on the possible non-inferiority of the Hiprex arm, compared to the nitrofurantoin arm, in terms of 6-month freedom from UTI recurrence. The proportions of patients with at least one UTI recurrence (with 95% CIs) in the 2 study arms will be calculated. Logistic regression with ‘treatment group’ as the only covariate will be employed to draw inference on the possible non-inferiority of Hiprex treatment compared to the nitrofurantoin treatment. The odds ratio (with 95% CIs) will be calculated with the nitrofurantoin arm as the reference group. Appropriate parametric or non-parametric statistical techniques will be employed to analyse the data for secondary aims of the study.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Advised by ethics committee underpowered study
Protocol was reviewed by independent statistician and the number required to achieve power was very large
Date of first participant enrolment
Anticipated
3/07/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
264
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7864 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [2] 7865 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 7866 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 15811 0
3084 - Heidelberg
Recruitment postcode(s) [2] 15812 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 296227 0
Hospital
Name [1] 296227 0
Mercy Hospital for Women - Urogynaecology Department
Country [1] 296227 0
Australia
Funding source category [2] 296252 0
Hospital
Name [2] 296252 0
Monash Medical Centre - Pelvic Floor Unit
Country [2] 296252 0
Australia
Funding source category [3] 296253 0
Hospital
Name [3] 296253 0
Austin Hospital - Infectious Diseases Department
Country [3] 296253 0
Australia
Primary sponsor type
Hospital
Name
Mercy Hospital for Women- Urogynaecology department
Address
163 Studley Road, Heidelberg, VIC 3084
Country
Australia
Secondary sponsor category [1] 295168 0
None
Name [1] 295168 0
N/A
Address [1] 295168 0
N/A
Country [1] 295168 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 297466 0
Mercy Hospital for Women Ethics committee
Ethics committee address [1] 297466 0
Ethics committee country [1] 297466 0
Australia
Date submitted for ethics approval [1] 297466 0
09/04/2017
Approval date [1] 297466 0
Ethics approval number [1] 297466 0
not received yet

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1646 1646 0 0
/AnzctrAttachments/372768-Q-Recurrent UTI Sx.doc (Other)
Attachments [2] 1661 1661 0 0
/AnzctrAttachments/372768-Hiprex vs Nitrofurantoin rUTI proposal-Final Version.docx (Protocol)

Contacts
Principal investigator
Name 74130 0
Dr PAYAM NIKPOOR
Address 74130 0
MERCY HOSPITAL FOR WOMEN
DEPARTMENT OF UROGYNAECOLOGY
163 STUDLEY ROADM HEIDELBERG VIC 3084 AUSTRALIA
Country 74130 0
Australia
Phone 74130 0
+61384584500
Fax 74130 0
Email 74130 0
payam.nikpoor@gmail.com
Contact person for public queries
Name 74131 0
Christine Murray
Address 74131 0
MERCY HOSPITAL FOR WOMEN
DEPARTMENT OF UROGYNAECOLOGY
163 STUDLEY ROADM HEIDELBERG VIC 3084 AUSTRALIA
Country 74131 0
Australia
Phone 74131 0
+61384584500
Fax 74131 0
Email 74131 0
cjmurray@mercy.com.au
Contact person for scientific queries
Name 74132 0
PAYAM NIKPOOR
Address 74132 0
MERCY HOSPITAL FOR WOMEN
DEPARTMENT OF UROGYNAECOLOGY
163 STUDLEY ROADM HEIDELBERG VIC 3084 AUSTRALIA
Country 74132 0
Australia
Phone 74132 0
+61384584500
Fax 74132 0
Email 74132 0
payam.nikpoor@gmail.com

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
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