Heparin Intraoperative Instillation for Lower Urinary Tract Symptoms After Benign Hysterectomy

NCT03633994 | Unknown Phase 2 FDA Drug

• 1 other identifier: TCH #18-12
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lower Urinary Tract Symptoms; Postoperative Urinary Tract Infection

Keywords

Randomized controlled trial; Heparin instillation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Postoperative antibiotic use

  Postoperative day 1 to 14

• Postoperative patient satisfaction

  Postoperative day 14

Study Arms (2)

Heparin Bladder Instillation

EXPERIMENTAL

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

Normal Saline Bladder Instillation

PLACEBO COMPARATOR

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

Interventions

Heparin DRUG

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%.

Heparin Bladder Instillation

Normal saline DRUG

Normal saline bladder instillation

Normal Saline Bladder Instillation

Eligibility Criteria

• Age: 18 Years - 85 Years
• Gender Eligibility Details: Patients undergoing benign hysterectomy
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 85-years old
• scheduled to undergo a benign hysterectomy

You may not qualify if:

• 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

Sponsors & Collaborators

• The Christ Hospital: lead

Study Sites (1)

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Related Publications (29)

• Ablove T, Patankar M, Seo S. Prevention of recurrent urinary tract infections by intravesical administration of heparin: a pilot study. Ther Adv Urol. 2013 Dec;5(6):303-9. doi: 10.1177/1756287213504804.

  PMID: 24294288 RESULT

• Albo ME, Richter HE, Brubaker L, Norton P, Kraus SR, Zimmern PE, Chai TC, Zyczynski H, Diokno AC, Tennstedt S, Nager C, Lloyd LK, FitzGerald M, Lemack GE, Johnson HW, Leng W, Mallett V, Stoddard AM, Menefee S, Varner RE, Kenton K, Moalli P, Sirls L, Dandreo KJ, Kusek JW, Nyberg LM, Steers W; Urinary Incontinence Treatment Network. Burch colposuspension versus fascial sling to reduce urinary stress incontinence. N Engl J Med. 2007 May 24;356(21):2143-55. doi: 10.1056/NEJMoa070416. Epub 2007 May 21.

  PMID: 17517855 RESULT

• Anand M, Wang C, French J, Isaacson-Schmid M, Wall LL, Mysorekar IU. Estrogen affects the glycosaminoglycan layer of the murine bladder. Female Pelvic Med Reconstr Surg. 2012 May-Jun;18(3):148-52. doi: 10.1097/SPV.0b013e31824b76bd.

  PMID: 22543765 RESULT

• Ciani O, Arendsen E, Romancik M, Lunik R, Costantini E, Di Biase M, Morgia G, Fragala E, Roman T, Bernat M, Guazzoni G, Tarricone R, Lazzeri M. Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study. BMJ Open. 2016 Mar 31;6(3):e009669. doi: 10.1136/bmjopen-2015-009669.

  PMID: 27033958 RESULT

• Clayson D, Wild D, Doll H, Keating K, Gondek K. Validation of a patient-administered questionnaire to measure the severity and bothersomeness of lower urinary tract symptoms in uncomplicated urinary tract infection (UTI): the UTI Symptom Assessment questionnaire. BJU Int. 2005 Aug;96(3):350-9. doi: 10.1111/j.1464-410X.2005.05630.x.

  PMID: 16042729 RESULT

• Cohen SL, Ajao MO, Clark NV, Vitonis AF, Einarsson JI. Outpatient Hysterectomy Volume in the United States. Obstet Gynecol. 2017 Jul;130(1):130-137. doi: 10.1097/AOG.0000000000002103.

  PMID: 28594764 RESULT

• Damiano R, Quarto G, Bava I, Ucciero G, De Domenico R, Palumbo MI, Autorino R. Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial. Eur Urol. 2011 Apr;59(4):645-51. doi: 10.1016/j.eururo.2010.12.039. Epub 2011 Jan 18.

  PMID: 21272992 RESULT

• Desai VB, Xu X. An update on inpatient hysterectomy routes in the United States. Am J Obstet Gynecol. 2015 Nov;213(5):742-3. doi: 10.1016/j.ajog.2015.07.038. Epub 2015 Jul 28. No abstract available.

  PMID: 26226555 RESULT

• Dieter AA, Amundsen CL, Edenfield AL, Kawasaki A, Levin PJ, Visco AG, Siddiqui NY. Oral antibiotics to prevent postoperative urinary tract infection: a randomized controlled trial. Obstet Gynecol. 2014 Jan;123(1):96-103. doi: 10.1097/AOG.0000000000000024.

  PMID: 24463669 RESULT

• Elkadry EA, Kenton KS, FitzGerald MP, Shott S, Brubaker L. Patient-selected goals: a new perspective on surgical outcome. Am J Obstet Gynecol. 2003 Dec;189(6):1551-7; discussion 1557-8. doi: 10.1016/s0002-9378(03)00932-3.

  PMID: 14710061 RESULT

• Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003 Feb;49(2):53-70. doi: 10.1067/mda.2003.7.

  PMID: 12601337 RESULT

• Gagyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K, Hummers-Pradier E. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ. 2015 Dec 23;351:h6544. doi: 10.1136/bmj.h6544.

  PMID: 26698878 RESULT

• Generali JA, Cada DJ. Intravesical heparin: interstitial cystitis (painful bladder syndrome). Hosp Pharm. 2013 Nov;48(10):822-4. doi: 10.1310/hpj4810-822.

  PMID: 24421434 RESULT

• Giesen LG, Cousins G, Dimitrov BD, van de Laar FA, Fahey T. Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs. BMC Fam Pract. 2010 Oct 24;11:78. doi: 10.1186/1471-2296-11-78.

  PMID: 20969801 RESULT

• Givens CD, Wenzel RP. Catheter-associated urinary tract infections in surgical patients: a controlled study on the excess morbidity and costs. J Urol. 1980 Nov;124(5):646-8. doi: 10.1016/s0022-5347(17)55596-2.

  PMID: 7452793 RESULT

• Jackson D, Higgins E, Bracken J, Yandell PM, Shull B, Foster RT Sr. Antibiotic prophylaxis for urinary tract infection after midurethral sling: a randomized controlled trial. Female Pelvic Med Reconstr Surg. 2013 May-Jun;19(3):137-41. doi: 10.1097/SPV.0b013e318285ba53.

  PMID: 23611930 RESULT

• Karp NE, Kobernik EK, Kamdar NS, Fore AM, Morgan DM. Length of Catheter Use After Hysterectomy as a Risk Factor for Urinary Tract Infection. Female Pelvic Med Reconstr Surg. 2018 Nov/Dec;24(6):430-434. doi: 10.1097/SPV.0000000000000486.

  PMID: 28914703 RESULT

• Lake AG, McPencow AM, Dick-Biascoechea MA, Martin DK, Erekson EA. Surgical site infection after hysterectomy. Am J Obstet Gynecol. 2013 Nov;209(5):490.e1-9. doi: 10.1016/j.ajog.2013.06.018. Epub 2013 Jun 13.

  PMID: 23770467 RESULT

• Lakeman MM, van der Vaart CH, Roovers JP; HysVA study group. Hysterectomy and lower urinary tract symptoms: a nonrandomized comparison of vaginal and abdominal hysterectomy. Gynecol Obstet Invest. 2010;70(2):100-6. doi: 10.1159/000297507. Epub 2010 Mar 19.

  PMID: 20299800 RESULT

• Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007 Sep;7(9):678-89. doi: 10.1038/nri2156.

  PMID: 17717539 RESULT

• Lusardi G, Lipp A, Shaw C. Antibiotic prophylaxis for short-term catheter bladder drainage in adults. Cochrane Database Syst Rev. 2013 Jul 3;2013(7):CD005428. doi: 10.1002/14651858.CD005428.pub2.

  PMID: 23824735 RESULT

• Nomiya A, Naruse T, Niimi A, Nishimatsu H, Kume H, Igawa Y, Homma Y. On- and post-treatment symptom relief by repeated instillations of heparin and alkalized lidocaine in interstitial cystitis. Int J Urol. 2013 Nov;20(11):1118-22. doi: 10.1111/iju.12120. Epub 2013 Feb 22.

  PMID: 23432185 RESULT

• Palsson M, Stjerndahl JH, Granasen G, Lofgren M, Sundfeldt K. Patient-reported lower urinary tract symptoms after hysterectomy or hysteroscopy: a study from the Swedish Quality Register for Gynecological Surgery. Int Urogynecol J. 2017 Sep;28(9):1341-1349. doi: 10.1007/s00192-017-3268-9. Epub 2017 Jan 23.

  PMID: 28116468 RESULT

• Parsons CL, Zupkas P, Proctor J, Koziol J, Franklin A, Giesing D, Davis E, Lakin CM, Kahn BS, Garner WJ. Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis. J Sex Med. 2012 Jan;9(1):207-12. doi: 10.1111/j.1743-6109.2011.02542.x. Epub 2011 Nov 14.

  PMID: 22082303 RESULT

• Pham T, Kenton K, Mueller E, Brubaker L. New pelvic symptoms are common after reconstructive pelvic surgery. Am J Obstet Gynecol. 2009 Jan;200(1):88.e1-5. doi: 10.1016/j.ajog.2008.08.010. Epub 2008 Oct 9.

  PMID: 18845285 RESULT

• Qin C, de Oliveira G, Hackett N, Kim JY. Surgical duration and risk of Urinary Tract Infection: An analysis of 1,452,369 patients using the National Surgical Quality Improvement Program (NSQIP). Int J Surg. 2015 Aug;20:107-12. doi: 10.1016/j.ijsu.2015.05.051. Epub 2015 Jun 6.

  PMID: 26054658 RESULT

• Shepherd AK, Pottinger PS. Management of urinary tract infections in the era of increasing antimicrobial resistance. Med Clin North Am. 2013 Jul;97(4):737-57, xii. doi: 10.1016/j.mcna.2013.03.006. Epub 2013 Apr 29.

  PMID: 23809723 RESULT

• Thakar R, Ayers S, Clarkson P, Stanton S, Manyonda I. Outcomes after total versus subtotal abdominal hysterectomy. N Engl J Med. 2002 Oct 24;347(17):1318-25. doi: 10.1056/NEJMoa013336.

  PMID: 12397189 RESULT

• Wald HL, Ma A, Bratzler DW, Kramer AM. Indwelling urinary catheter use in the postoperative period: analysis of the national surgical infection prevention project data. Arch Surg. 2008 Jun;143(6):551-7. doi: 10.1001/archsurg.143.6.551.

  PMID: 18559747 RESULT

MeSH Terms

Conditions

Lower Urinary Tract Symptoms

Interventions

Heparin; Saline Solution

Condition Hierarchy (Ancestors)

Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Hoi Tik H Yuen, MD

CONTACT

(513) 463-2500; hoitik.yuen@thechristhospital.com

James Whiteside, MD

CONTACT

(513) 475-8248

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Female Pelvic Medicine and Reconstructive Surgery Fellow

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 16, 2018
• Study Start: August 20, 2018
• Primary Completion: December 31, 2019
• Study Completion: March 1, 2020
• Last Updated: October 10, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)