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This study is randomized double-blinded placebo-controlled trial to access oral Methenamine Hippurate (MH) in combination with cranberry capsules is superior to cranberry capsules alone in prevention of UTI in patients with transient post-operative urinary retention requiring a Foley catheter after pelvic reconstructive surgery.
Urinary tract infections (UTIs) are one of the most common bacterial infections in women. It is estimated that 1.6 billion dollars are spent on UTI treatment each year. Antibiotics have been the mainstay of treatment of UTIs, however frequent use has increased the prevalence of antibiotic resistant organisms. Therefore, focus has shifted to non-antibiotic therapy for UTI prophylaxis.
Methenamine Hippurate (MH) has been studied for decades due to its potential role in prevention of UTI. While not technically an antibiotic, MH works via its bacteriostatic action in the bladder. Benefits of MH are the lack of development of resistance, and the selective nature of this drug to the urinary system only. However, MH is best used in conjunction with an acidifying agent to increase its bioavailability (such as cranberry capsules or other acidic products). The usage of MH has been studied in various populations, has been seen to be effective in short-term catheterization. Usage of cranberry as prophylaxis for UTI is controversial; however, results have been favorable in the post-operative gynecological population.
Post-operative urinary retention (POUR) occurs frequently in patients who undergo incontinence and pelvic prolapse surgery. Although the definition of POUR can vary between clinicians, it is reported as 2.5-24% to as high as 43% after tension-free transvaginal mesh sling placement. This population is at also at high risk for UTI due to advanced age and menopausal status. Moreover, using a catheter longer than 2 days incurs a 2-fold increased risk of development of UTI with an estimated 5% increase in bacteriuria each day of catheterization.
In hopes to decrease the overuse of antibiotics and decrease the likelihood of antibiotic resistance, we propose that the use of MH and cranberry can reflect a potential benefit in this population of short-term indwelling Foley catheter use and help reduce the incidence of post-operative UTI after pelvic surgery.
The patients will then be randomized to either receive cranberry capsules and placebo OR cranberry capsules and Methenamine Hippurate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methenamine Hippurate with Cranberry | Experimental | Subjects will be instructed to take Methenamine Hippurate 1 g tablet ( 1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. |
|
| Placebo with Cranberry | Placebo Comparator | Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methenamine Hippurate 1 g tablet | Drug | Methenamine Hippurate (study drug) is an FDA approved medication in the prevention of UTI. Methenamine Hippurate 1g contains Hippuric acid salt of Methenamine (hexamethylene tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, FD&C Yellow No. 5 (tartrazine) (www.iodine.com/drug/hiprex/fda-package-insert). |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Urinary Track Infection (UTI) | Incidence of UTIs will be diagnosed at one week post-op visit. | From surgery to one week post-op visit, approximately 1 week post surgery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rachel Pauls, MD | TriHealth - Cincinnati Urogynecology Associates | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Urogynecology Associates | Cincinnati | Ohio | 45220 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35272334 | Derived | Tam TY, Aldrich ER, Crisp CC, Yook E, Yeung J, Pauls RN. Methenamine Hippurate With Cranberry Capsules Versus Cranberry Alone for Urinary Tract Infection Prevention in a Short-Term Indwelling Foley Catheter Population After Urogynecologic Surgery: A Double-Blinded Randomized Controlled Trial. Female Pelvic Med Reconstr Surg. 2022 Mar 1;28(3):e55-e61. doi: 10.1097/SPV.0000000000001147. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Methenamine Hippurate With Cranberry | Subjects will be instructed to take Methenamine Hippurate 1 g tablet ( 1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Methenamine Hippurate 1 g tablet: Methenamine Hippurate (study drug) is an FDA approved medication in the prevention of UTI. Methenamine Hippurate 1g contains Hippuric acid salt of Methenamine (hexamethylene tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, FD&C Yellow No. 5 (tartrazine) (www.iodine.com/drug/hiprex/fda-package-insert). |
| FG001 | Placebo With Cranberry | Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016. Placebo tablet: Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Methenamine Hippurate With Cranberry | Subjects will be instructed to take Methenamine Hippurate 1 g tablet ( 1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Methenamine Hippurate 1 g tablet: Methenamine Hippurate (study drug) is an FDA approved medication in the prevention of UTI. Methenamine Hippurate 1g contains Hippuric acid salt of Methenamine (hexamethylene tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, FD&C Yellow No. 5 (tartrazine) (www.iodine.com/drug/hiprex/fda-package-insert). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Urinary Track Infection (UTI) | Incidence of UTIs will be diagnosed at one week post-op visit. | Posted | Count of Participants | Participants | From surgery to one week post-op visit, approximately 1 week post surgery |
|
6 week postop
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methenamine Hippurate With Cranberry | Subjects will be instructed to take Methenamine Hippurate 1 g tablet ( 1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Methenamine Hippurate 1 g tablet: Methenamine Hippurate (study drug) is an FDA approved medication in the prevention of UTI. Methenamine Hippurate 1g contains Hippuric acid salt of Methenamine (hexamethylene tetramine), Magnesium Stearate, Povidone, Saccharin Sodium, FD&C Yellow No. 5 (tartrazine) (www.iodine.com/drug/hiprex/fda-package-insert). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rachel Pauls | TriHealth | 513-463-4300 | Rachel_Pauls@trihealth.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 20, 2021 | Aug 11, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014552 | Urinary Tract Infections |
| D056887 | Pelvic Organ Prolapse |
| ID | Term |
|---|---|
| D007239 | Infections |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C011481 | methenamine hippurate |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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This is randomized double-blinded placebo-controlled trial, and both patients and investigators are blinded. However, a research nurse will not be blinded to the group allocation, and the research nurse will order each patient's medication to the inpatient pharmacy based on the study randomization scheme.
|
| Placebo tablet | Drug | Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient. |
|
| BG001 | Placebo With Cranberry | Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016. Placebo tablet: Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Placebo With Cranberry |
Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016. Placebo tablet: Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient. |
|
|
| 0 |
| 93 |
| 0 |
| 93 |
| 0 |
| 93 |
| EG001 | Placebo With Cranberry | Subjects will be instructed to take Placebo tablet (1 tablet twice daily) with Cranberry supplementation (1 tablet twice daily) by mouth starting at time of discharge for 6-8 days. Cranberry capsules were incorporated into the standard practice of Cincinnati Urogynecology Associates, TriHealth Inc in mid-March 2016. Placebo tablet: Placebo is a tablet that will be provided to you that looks like the study drug but does not contain any medication. These pills are comprised of gelatin and minimal amounts of lactose powder. The pills are designed to have no effect on the patient. | 0 | 89 | 0 | 89 | 0 | 89 |
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D011391 | Prolapse |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |