Short-course Methenamine Hippurate for Prevention of Post-operative UTI

NCT ID: NCT02358993

Last Updated: 2022-02-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

201 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2020-09-30

Brief Summary

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The investigators will determine the efficacy of an innovative short regimen of methenamine hippurate on prevention of post-operative UTI in patients requiring short-term catheterization after pelvic reconstructive surgery through a single-blind, randomized controlled trial. Primary outcome will be the rate of symptomatic UTI within 3 weeks of catheter removal. The investigators will study cost-effectiveness, antibiotic resistance profiles, and adverse drug effects. Findings may reduce antibiotic use and nosocomial UTIs.

Detailed Description

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Prevention of post-operative urinary tract infections (UTI) is becoming important for both the individual patient and the health system. Complications of UTI include pyelonephritis and bacteremia, requiring hospitalization and parenteral antibiotics. Additionally, recurrent exposure to antibiotics commonly given for UTIs increases the risk of antibiotic resistance to uropathogens. UTIs also increase economic burdens on the health care system, with each episode costing nearly 600 dollars. UTIs associated with catheterization are particularly costly for hospitals, resulting in decreased hospital quality measures and lack of compensation.

This is particularly important after pelvic reconstructive surgery, as reported rates of UTI reach up to 20-25%. Urinary retention requiring short-term indwelling catheterization, common in these women, contributes to the risk of UTIs by increasing the risk of bacteriuria by 5-10% per day and through the dislodging of bacterial colonies during catheter removal. Balancing prevention and resistance and cost is key. A meta-analysis by Marschall et al indicated the benefit of a short dose of antibiotic prophylaxis at catheter removal in general post-surgical patients. However, data is lacking on the effects of daily antibiotic prophylaxis on resistance and cost.

A possible alternative to antibiotics presents itself in methenamine hippurate, a urinary antiseptic which forms formaldehyde in the presence of acidic urine. It is relatively inexpensive, and does not induce resistance in vivo. Prior studies have shown that daily use of methenamine can decrease the risk of post-operative UTI.

The purpose of our study was to investigate the efficacy of a short course of methenamine hippurate at catheter removal to that of a short course of ciprofloxacin in prevention of UTIs after short-term indwelling catheterization. Additionally, we investigated factors that influence post-operative UTIs, the rate of culture-proven UTIs after prophylaxis, the antibiotic resistance profile of those undergoing prophylaxis, and the cost effectiveness of prophylaxis.

Conditions

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Urinary Tract Infections Catheter-Related Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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Methenamine

Methenamine hippurate is a medication that exhibits antibacterial activity by converting to formaldehyde in the presence of acidic urine. It is currently FDA approved for the prophylaxis of recurrent urinary tract infections. It has been previously used in studies for prevention of UTI after gynecologic surgery. Dosage will be methenamine hippurate 1g, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal.

Group Type EXPERIMENTAL

methenamine hippurate

Intervention Type DRUG

A urinary antiseptic used for prevention of UTI

Ciprofloxacin

Ciprofloxacin is a commonly used antibiotic commonly used for prevention of UTI after catheterization. It belongs to a class of antibiotics known as the fluoroquinolones. Dosage will be ciprofloxacin 500 mg, 1 tablet by mouth every 12 hours for 24 hours (total of two doses), with the first dose taken at least one hour prior to catheter removal.

Group Type ACTIVE_COMPARATOR

Ciprofloxacin

Intervention Type DRUG

An antibiotic used for treatment and prevention of UTI

Interventions

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methenamine hippurate

A urinary antiseptic used for prevention of UTI

Intervention Type DRUG

Ciprofloxacin

An antibiotic used for treatment and prevention of UTI

Intervention Type DRUG

Other Intervention Names

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Hiprex Cipro

Eligibility Criteria

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Inclusion Criteria

* female;
* patients who are able to read and write English;
* 18 years of age or older;
* underwent surgery for pelvic organ prolapse, urinary incontinence, or both;
* require post-operative short-term transurethral catheterization for greater than 24 hours.

Exclusion Criteria

* patients undergoing surgical intervention for sacral neuromodulation, or mesh excision;
* patients requiring long-term catheterization secondary to injury to the urinary tract;
* patients who pass their post-operative trial void and thus, do not require additional catheterization;
* patients requiring catheterization for less than 24 hours;
* pregnant patients;
* patients who are breast-feeding;
* allergy to methenamine hippurate or fluroquinolones (either ciprofloxacin or levofloxacin);
* impaired renal or hepatic function;
* pre-operative urinary retention;
* patients who are currently using sulfonamides;
* patients who have severe dehydration;
* patients using tizanidine;
* patients sensitive to quinolones class;
* patients using theophylline; patients with myasthenia gravis;
* patients with prolongation of QT interval.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine M Chu, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Lily Arya, MD, MS

Role: STUDY_DIRECTOR

University of Pennsylvania

Daniel Lee, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Chestnut Hill Hospital

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Schiotz HA. Comparison of 1 and 3 days' transurethral Foley catheterization after retropubic incontinence surgery. Int Urogynecol J Pelvic Floor Dysfunct. 1996;7(2):98-101. doi: 10.1007/BF01902381.

Reference Type BACKGROUND
PMID: 8798095 (View on PubMed)

Schiotz HA, Guttu K. Value of urinary prophylaxis with methenamine in gynecologic surgery. Acta Obstet Gynecol Scand. 2002 Aug;81(8):743-6. doi: 10.1080/j.1600-0412.2002.810810.x.

Reference Type BACKGROUND
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Hakvoort RA, Elberink R, Vollebregt A, Ploeg T, Emanuel MH. How long should urinary bladder catheterisation be continued after vaginal prolapse surgery? A randomised controlled trial comparing short term versus long term catheterisation after vaginal prolapse surgery. BJOG. 2004 Aug;111(8):828-30. doi: 10.1111/j.1471-0528.2004.00181.x.

Reference Type BACKGROUND
PMID: 15270931 (View on PubMed)

Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, Forward KR, Low DE, Cheang M. How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med. 1991 May 1;114(9):713-9. doi: 10.7326/0003-4819-114-9-713.

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Warren JW. Catheter-associated urinary tract infections. Infect Dis Clin North Am. 1987 Dec;1(4):823-54.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 15564006 (View on PubMed)

Wolf JS Jr, Bennett CJ, Dmochowski RR, Hollenbeck BK, Pearle MS, Schaeffer AJ; Urologic Surgery Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008 Apr;179(4):1379-90. doi: 10.1016/j.juro.2008.01.068. Epub 2008 Feb 20.

Reference Type BACKGROUND
PMID: 18280509 (View on PubMed)

ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009 May;113(5):1180-1189. doi: 10.1097/AOG.0b013e3181a6d011. No abstract available.

Reference Type BACKGROUND
PMID: 19384149 (View on PubMed)

Ghezzi F, Serati M, Cromi A, Uccella S, Salvatore S, Bolis P. Prophylactic single-dose prulifloxacin for catheter-associated urinary tract infection after tension-free vaginal tape procedure. Int Urogynecol J Pelvic Floor Dysfunct. 2007 Jul;18(7):753-7. doi: 10.1007/s00192-006-0233-4. Epub 2006 Nov 21.

Reference Type BACKGROUND
PMID: 17120175 (View on PubMed)

Rogers RG, Kammerer-Doak D, Olsen A, Thompson PK, Walters MD, Lukacz ES, Qualls C. A randomized, double-blind, placebo-controlled comparison of the effect of nitrofurantoin monohydrate macrocrystals on the development of urinary tract infections after surgery for pelvic organ prolapse and/or stress urinary incontinence with suprapubic catheterization. Am J Obstet Gynecol. 2004 Jul;191(1):182-7. doi: 10.1016/j.ajog.2004.03.088.

Reference Type BACKGROUND
PMID: 15295362 (View on PubMed)

Baertschi U, Kunz J. [Comparative study on the question of systemic chemoprophylaxis following gynecological surgery]. Schweiz Med Wochenschr. 1976 Mar 13;106(11):380-5. German.

Reference Type BACKGROUND
PMID: 1251156 (View on PubMed)

Gordon KA, Jones RN; SENTRY Participant Groups (Europe, Latin America, North America). Susceptibility patterns of orally administered antimicrobials among urinary tract infection pathogens from hospitalized patients in North America: comparison report to Europe and Latin America. Results from the SENTRY Antimicrobial Surveillance Program (2000). Diagn Microbiol Infect Dis. 2003 Apr;45(4):295-301. doi: 10.1016/s0732-8893(02)00467-4.

Reference Type BACKGROUND
PMID: 12730002 (View on PubMed)

Tyreman NO, Andersson PO, Kroon L, Orstam S. Urinary tract infection after vaginal surgery. Effect of prophylactic treatment with methenamine hippurate. Acta Obstet Gynecol Scand. 1986;65(7):731-3. doi: 10.3109/00016348609161491.

Reference Type BACKGROUND
PMID: 3544661 (View on PubMed)

Knoff T. [Methenamine hippurate. Short-term catheterization in gynecologic surgery. A double-blind comparison of Hiprex and placebo]. Tidsskr Nor Laegeforen. 1985 Mar 10;105(7):498-9. No abstract available. Norwegian.

Reference Type BACKGROUND
PMID: 3887639 (View on PubMed)

Ladehoff P, Jacobsen JC, Olsen H, Pedersen GT, Sorensen T. [The preventive effect of methenamine hippurate (Haiprex) on urinary infections after short-term catheterization. A clinical study]. Ugeskr Laeger. 1984 May 7;146(19):1433-4. No abstract available. Danish.

Reference Type BACKGROUND
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Strom JG Jr, Jun HW. Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde. Biopharm Drug Dispos. 1993 Jan;14(1):61-9. doi: 10.1002/bdd.2510140106.

Reference Type BACKGROUND
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Marschall J, Carpenter CR, Fowler S, Trautner BW; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ. 2013 Jun 11;346:f3147. doi: 10.1136/bmj.f3147.

Reference Type BACKGROUND
PMID: 23757735 (View on PubMed)

Sutkin G, Alperin M, Meyn L, Wiesenfeld HC, Ellison R, Zyczynski HM. Symptomatic urinary tract infections after surgery for prolapse and/or incontinence. Int Urogynecol J. 2010 Aug;21(8):955-61. doi: 10.1007/s00192-010-1137-x. Epub 2010 Mar 31.

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PMID: 20354678 (View on PubMed)

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.

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Turck M, Stamm W. Nosocomial infection of the urinary tract. Am J Med. 1981 Mar;70(3):651-4. doi: 10.1016/0002-9343(81)90590-8.

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Duclos JM, Larrouturou P, Sarkis P. Timing of antibiotic prophylaxis with cefotaxime for prostatic resection: better in the operative period or at urethral catheter removal? Am J Surg. 1992 Oct;164(4A Suppl):21S-23S. doi: 10.1016/s0002-9610(06)80053-x.

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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.

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Lee BS, Bhuta T, Simpson JM, Craig JC. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD003265. doi: 10.1002/14651858.CD003265.pub3.

Reference Type BACKGROUND
PMID: 23076896 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7265?hl=6550/

Methenamine. In: Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc. \[updated 2/1/14; accessed 2/21/14\].

http://www.micromedexsolutions.com/micromedex2/librarian/

Methenamine. In: Micromedex 2.0. Martindale - The Complete Drug Reference. Ann Arbor, MI: Truven Health Analytics. \[updated 8/20/2010; accessed 2/21/14\].

http://www.micromedexsolutions.com/micromedex2/librarian/

Nitrofurantoin. In: Micromedex 2.0. Martindale - The Complete Drug Reference. Ann Arbor, MI: Truven Health Analytics. \[updated 8/20/2010; accessed 2/21/14\].

http://www.micromedexsolutions.com/micromedex2/librarian/

Ciprofloxacin. In: Micromedex 2.0. Martindale - The Complete Drug Reference. Ann Arbor, MI: Truven Health Analytics. \[updated 8/20/2010; accessed 2/21/14\].

http://www.micromedexsolutions.com/micromedex2/librarian/

Sulfamethoxazole/Trimethoprim. In: Micromedex 2.0. Martindale - The Complete Drug Reference. Ann Arbor, MI: Truven Health Analytics. \[updated 8/20/2010; accessed 2/21/14\].

Other Identifiers

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820117

Identifier Type: -

Identifier Source: org_study_id

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