Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)

Sponsor

University of Oklahoma (Other)

Overall Status

Recruiting

CT.gov ID

NCT02246270

Collaborator

(none)

Enrollment

Location

Arms

72.1

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Urinary Tract Infections	Drug: Intravesical Heparin Other: Placebo	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Recurrent Urinary Tract Infections and Heparin: a Double-blind Randomized Trial (RUTIH Trial)

Actual Study Start Date :

Nov 28, 2017

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravesical heparin Recurrent UTI subject receives intravesical heparin once every week for 6 weeks	Drug: Intravesical Heparin Heparin bladder instillation Other Names: Intravesical heparin bladder instillation
Active Comparator: Placebo Recurrent UTI subject receives intravesical saline once every week for 6 weeks	Other: Placebo Intravesical saline

Arm

Intervention/Treatment

Experimental: Intravesical heparin

Recurrent UTI subject receives intravesical heparin once every week for 6 weeks

Drug: Intravesical Heparin

Heparin bladder instillation

Other Names:

Intravesical heparin bladder instillation

Active Comparator: Placebo

Recurrent UTI subject receives intravesical saline once every week for 6 weeks

Other: Placebo

Intravesical saline

Outcome Measures

Primary Outcome Measures

Change from Baseline in UTI rate at 6 months [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 [6 months]
Will measure change from baseline in median time to UTI recurrence at 6 months by statistical analysis

Other Outcome Measures

Change from Baseline in NGAL levels at 6 months(NGAL) levels after Heparin treatment [6 months]
Will measure change from baseline in NGAL levels at 6 months (NGAL) levels after Heparin treatment using statistical analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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