Heparin Intraoperative Instillation for Lower Urinary Tract Symptoms After Benign Hysterectomy

Study Overview
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Brief Summary
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This study will explore the application of placing heparin into the bladder via a catheter to decrease postoperative lower urinary tract symptoms (LUTS) and urinary tract infection (UTI) symptoms such as urinary frequency, urinary urgency, pain with urination, or difficulty voiding following hysterectomy (surgically removing the uterus). The investigators hypothesize that heparin bladder instillations will reduce LUTS, UTI symptoms, and improve patient satisfaction following hysterectomy.

Detailed Description
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Data Collection Subject demographics and history information will be obtained from The Christ Hospital Medical Center's electronic medical record. In addition, preoperative diagnosis, postoperative diagnosis, procedure performed, total operative time, estimated blood loss, intraoperative complications, anterior prolapse repair, use of cystoscopy, preoperative urinalysis, postoperative complications, uterine size, and any urine cultures collected within the 2 week postoperative period will also obtained from the electronic medical record. The post-operative lower urinary tract symptoms assessments will be collected, the paper records will be secured in a locker labeled with the study identification number, which will then be entered into EXCEL on a password secured database and the paper copy will be disposed of in the secure destruction station. Descriptive Analysis Simple statistics and demographics will be done across the two cohorts. Categorical variables will be analyzed using Chi-square while continuous variables (e.g. UTISA scores) will be analyzed using t-test so long as the distribution of the data are normal. Additional analyzes as appropriate will be done to identify group differences based on patient demographics (e.g. age, concomitant procedures, surgeon, estrogen use, foley catheter placement, etc). Data Analysis and Data Monitoring The UTISA survey and VAS pain scale both result a continuous variable that between the two cohorts will be compared using a t-Test provided the results distribution is normal. Antibiotic use or self-reported UTI rates are nominal variables that across the cohorts would be compared using a X2. Data analysis will be performed using statistical software (JMP 13.2.0, SAS Institute Inc., Cary NC, USA). The data will be assembled into a password protected EXCEL (Microsoft, Redmond WA, USA) spreadsheet. A separate password protected spreadsheet will link the study ID and the enrolled patient's MRN. Analysis would be done only on the de-identified data. Data Storage and Confidentiality Study data will be managed in a password-protected EXCEL (Microsoft, Redmond WA, USA) spreadsheet on a password-protected computer. A separate password protected spreadsheet linking the study ID and MRN will be kept on a separate password-protected secure drive. This key file will be securely destroyed when the data has been fully analyzed. Paper records including consent will be in a locked research drawer, in the designated locked office. The investigators will dispose of any paper documents after data has been analyzed using the CINTAS Secure Destruction Station. Sample Size The symptom with the highest sensitivity and specificity to predict a UTI is dysuria. A study in 2013 demonstrated a 50% reduction in UTIs among heparin treated patients, the investigators estimated an effect size of 0.6, assuming mean UTISA dysuria scores of 2 and 1 among the untreated and treated cohorts assessed on post-operative day 1. Assuming an α of 0.05 and 80% power, the investigators estimate requiring 45 subjects per study arm totaling 90 patients. Assuming at least 15% attrition in each arm, the investigators estimate needing to enroll at least 52 patients per study arm to a total of 104 patients. Plans for recruitment of subjects No advertisement will be used. The recruitment will take at the time of surgical consent, via phone after patient is identified at the time of preoperative visit, or on the day of surgery.

Official Title
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Heparin Intraoperative Instillation for Lower Urinary Tract Symptoms After Benign Hysterectomy: A Randomized Controlled Trial

Conditions
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Lower Urinary Tract Symptoms, Postoperative Urinary Tract Infection

Intervention / Treatment
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* Drug: Heparin
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 85-years old scheduled to undergo a benign hysterectomy Exclusion Criteria: non-English speakers current use of anticoagulants or thrombolytic agents known adverse reaction or hypersensitivity to heparin history of or active genitourinary tract cancer (bladder, uterine, cervical, ovarian or vaginal) history of neurogenic bladder pelvic irradiation chemical cystitis pregnancy antibiotic use within the past 30 days Surgical procedures involving: anterior or posterior colporrhaphy, vaginal mesh excision, fistula repair, diverticulum repair, urethral reconstruction, planned or incidental cystotomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heparin Bladder Instillation<br>At the completion of the scheduled benign hysterectomy, intravesicular bladder instillation containing 40,000U of heparin (40mL of 10,000U heparin/10mL) will be administered be introduced in a retrograde fashion by gravity via Foley catheter. The Foley catheter will be clamped for 30 minutes approximately 1cm from the vaginal opening. | Drug: Heparin<br>* Heparin is a readily available glycosaminoglycan (GAG) chemically similar to hyaluronic acid and chondroitin sulfate that is currently used to treat chronic painful bladder or interstitial cystitis. Heparin intravesical treatment is an inexpensive second-line treatment for chronic painful bladder, characterized by urinary frequency, urgency and pain. Heparin has been shown to re-establish the bladder urothelial GAG layer and as already noted was shown to reduce recurrent urinary tract infections by 50%.<br>|
| Placebo Comparator: Normal Saline Bladder Instillation<br>Patients randomized to the control group will undergo intravesical instillation with 40mL of normal saline. The Foley catheter will be clamped for 30 minutes approximately 1cm from the vaginal opening. | Drug: Normal saline<br>* Normal saline bladder instillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower urinary tract symptoms | lower urinary tract symptoms such as urgency, frequency, dysuria, and hematuria measured by the Urinary Tract Infection Symptoms Assessment Questionnaire (UTISA) | Postoperative day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative antibiotic use | Obtained via phone interview | Postoperative day 1 to 14 | 
| Postoperative patient satisfaction | Surgical Satisfaction Questionnaire (SSQ-8) assessment conducted via phone interview | Postoperative day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized controlled trial, Heparin instillation