Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)
Primary Purpose
Recurrent Urinary Tract Infections
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intravesical Heparin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Recurrent Urinary Tract Infections
Eligibility Criteria
Inclusion Criteria:
Women aged 18-85 with history of recurrent urinary tract infections.
- Definition of Recurrent UTI: if experienced either more than 3 symptomatic UTI episodes in the past year (including the index infection) or 2 such episodes in the past 6 months.
- Definition of UTI: >103 cfu/mL of a uropathogen in midstream urine culture from a woman experiencing more than 2 symptoms of cystitis (dysuria, urgency, frequency, suprapubic pain, or hematuria) or, in the absence of a culture, demonstration of pyuria on urinalysis and more than 2 urinary symptoms, as well as complete and rapid resolution of symptoms in response to antibiotic therapy for UTI.
Exclusion Criteria:
- Taking any anticoagulant such as warfarin sodium, heparin
- Taking any thrombolytic agent such as a tissue plasminogen activator or streptokinase
- Known aneurysm, thrombocytopenia, hemorrhagic disease, hemophilia, gastrointestinal ulceration, polyps, or diverticula
- Known hypersensitivity to heparin
- History of, or currently has neurogenic bladder, pelvic irradiation or chemical cystitis
- Presence of urethral, pelvic, or rectal carcinoma, Benign or malignant bladder tumors
- Tuberculous cystitis, urinary schistosomiasis
- Bladder or ureteral calculi, urethral or bladder obstruction, augmentation cystoplasty, cystectomy, supratrigonal denervation of the bladder (cystolysis), neurectomy, or implanted peripheral nerve stimulator that has affected bladder function; Microscopic hematuria as defined as > 5 red blood cells (RBC) /high power field at baseline visit without a negative workup within the last year
- Positive pregnancy test at the baseline visit, are pregnant or lactating, or are planning to become pregnant during the study period
- Have history of uterine, cervical or vaginal cancer during the past 3 years
- Clinically significant vaginitis at baseline visit
Sites / Locations
- University of Oklahoma-Tulsa OB/GYN Dept and OU-PhysiciansRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intravesical heparin
Placebo
Arm Description
Recurrent UTI subject receives intravesical heparin once every week for 6 weeks
Recurrent UTI subject receives intravesical saline once every week for 6 weeks
Outcomes
Primary Outcome Measures
Change from Baseline in UTI rate at 6 months
Will measure change from baseline in UTI rate at 6 months using statistical methods
Secondary Outcome Measures
Change from Baseline in median time to UTI recurrence at 6 months
Will measure change from baseline in median time to UTI recurrence at 6 months by statistical analysis
Full Information
NCT ID
NCT02246270
First Posted
September 15, 2014
Last Updated
October 31, 2022
Sponsor
University of Oklahoma
1. Study Identification
Unique Protocol Identification Number
NCT02246270
Brief Title
Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)
Official Title
Recurrent Urinary Tract Infections and Heparin: a Double-blind Randomized Trial (RUTIH Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 28, 2017 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oklahoma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Urinary Tract Infections (UTIs) are the second most common infection in the body. UTIs account for five percent of all visits to primary care physicians. Many women who have had a UTI will develop recurring urinary tract infections. Recent studies suggest that some women who suffer from recurrent UTIs have urinary tracts that allow bacteria to adhere to it more readily than others. Women who suffered from bladder inflammation and recurrent UTIs were noted to have reduced UTIs and bladder inflammation with heparin bladder instillations. Heparin is a highly-sulfated glycosaminoglycan and stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, in addition to anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials. The central question the research is intended to answer is does Heparin bladder instillations decrease UTI rates in patients.
Detailed Description
Primary Objectives: The specific aims of this study are to 1) demonstrate that Heparin bladder instillations reduce the number of UTI episodes; 2) demonstrate Heparin bladder instillations increase median intervals between UTI; and 3) demonstrate that Heparin bladder instillations decrease urine inflammatory (NGAL) levels. Study Design: This study will be a randomized, double-blind, placebo-controlled trial of subjects treated for documented recurrent urinary tract infections with heparin bladder instillation versus sterile saline instillations. The study recruits women (n = 30) with 3 or more UTI episodes in one year from the patient population at The University of Oklahoma Health Sciences Center (OUHSC) and The University of Oklahoma-Tulsa (OU-Tulsa) and randomly assigns them to treatment as usual care with sterile saline instillation (n =15) or treatment as usual with heparin bladder instillations (n = 15). Subjects are given 6 weekly bladder instillations with interval follow-ups; the primary outcome measures are number of UTI episodes during the six month study period and a survival analysis assesses time to the next UTI. The usual care of this study is antibiotic treatment for UTI only. Urine samples will be collected at certain intervals. Analysis: We will seek a statistically significant difference of the recurrent UTI rate for 6 months between heparin instillation and sterile saline instillation group. Assuming Recurrent UTI rate of sterile saline bladder instillation is 2.3.3 UTI episodes per six months, a 35% reduction in the recurrent UTI rate is deemed significant based on previous literature. A sample size 30 (15 for each group) will achieve 60% power to detect a 35% reduction in recurrent UTI rate at a 0.05 significance level. Allowing for a 25% drop out, a total of 30 subjects will be required. Significance: Recurrent UTIs are challenging to manage, especially if microbiological results are equivocal. In women who suffer from frequent recurrences, daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. However even with this traditional approach of continuous antibiotic for 6 to 12 months, the rate of UTI was only reduced during prophylaxis and the rate of UTI was unchanged after stopping antibiotic treatment. Increasing antibiotic resistance rates require immediate identification of innovative alternative prophylactic therapies. The lack of non-antibiotic therapies gives an opportunity to develop innovative strategies to decrease recurrent UTIs and decrease the burden of UTIs. This study will augment the current evidence available on the aggregate effects of a treatment that emphasizes the optimization of both antibiotic regimens and non-antibiotic interventions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Urinary Tract Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intravesical heparin
Arm Type
Experimental
Arm Description
Recurrent UTI subject receives intravesical heparin once every week for 6 weeks
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Recurrent UTI subject receives intravesical saline once every week for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Intravesical Heparin
Other Intervention Name(s)
Intravesical heparin bladder instillation
Intervention Description
Heparin bladder instillation
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Intravesical saline
Primary Outcome Measure Information:
Title
Change from Baseline in UTI rate at 6 months
Description
Will measure change from baseline in UTI rate at 6 months using statistical methods
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change from Baseline in median time to UTI recurrence at 6 months
Description
Will measure change from baseline in median time to UTI recurrence at 6 months by statistical analysis
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Change from Baseline in NGAL levels at 6 months(NGAL) levels after Heparin treatment
Description
Will measure change from baseline in NGAL levels at 6 months (NGAL) levels after Heparin treatment using statistical analysis
Time Frame
6 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women aged 18-85 with history of recurrent urinary tract infections.
Definition of Recurrent UTI: if experienced either more than 3 symptomatic UTI episodes in the past year (including the index infection) or 2 such episodes in the past 6 months.
Definition of UTI: >103 cfu/mL of a uropathogen in midstream urine culture from a woman experiencing more than 2 symptoms of cystitis (dysuria, urgency, frequency, suprapubic pain, or hematuria) or, in the absence of a culture, demonstration of pyuria on urinalysis and more than 2 urinary symptoms, as well as complete and rapid resolution of symptoms in response to antibiotic therapy for UTI.
Exclusion Criteria:
Taking any anticoagulant such as warfarin sodium, heparin
Taking any thrombolytic agent such as a tissue plasminogen activator or streptokinase
Known aneurysm, thrombocytopenia, hemorrhagic disease, hemophilia, gastrointestinal ulceration, polyps, or diverticula
Known hypersensitivity to heparin
History of, or currently has neurogenic bladder, pelvic irradiation or chemical cystitis
Presence of urethral, pelvic, or rectal carcinoma, Benign or malignant bladder tumors
Tuberculous cystitis, urinary schistosomiasis
Bladder or ureteral calculi, urethral or bladder obstruction, augmentation cystoplasty, cystectomy, supratrigonal denervation of the bladder (cystolysis), neurectomy, or implanted peripheral nerve stimulator that has affected bladder function; Microscopic hematuria as defined as > 5 red blood cells (RBC) /high power field at baseline visit without a negative workup within the last year
Positive pregnancy test at the baseline visit, are pregnant or lactating, or are planning to become pregnant during the study period
Have history of uterine, cervical or vaginal cancer during the past 3 years
Clinically significant vaginitis at baseline visit
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jameca R Price, MD
Phone
918-660-8350
Email
Jameca-Price@ouhsc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jameca R. Price, MD
Organizational Affiliation
University of Oklahoma
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oklahoma-Tulsa OB/GYN Dept and OU-Physicians
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jameca R Price, MD
Phone
918-660-8350
Email
Jameca-Price@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Jameca R. Price, MD
12. IPD Sharing Statement
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Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)
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