Pelvic Organ Prolapse, Urinary Retention Postoperative, Urinary Tract Infections
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGMethenamine 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).
DRUGPlacebo 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.
Sponsors
TriHealth Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients who undergo major pelvic organ prolapse surgery that are diagnosed with POUR via failed retrograde void trial and require an indwelling Foley catheter upon hospital discharge.
Exclusion criteria
* Unwillingness to participate in the study * Inability to understand English * Pregnant women * Patient personal history of nephrolithiasis, urogenital anomaly, neurogenic bladder, chronic renal insufficiency (GFR \<60 ml/min/1.73 m² or serum creatinine level \>1.03 for \>3months), sarcoidosis, and severe hepatic insufficiency * Currently (prior 3 months) undergoing medical management for recurrent UTI or interstitial cystitis * Active urinary tract infection * Patient history of taking Warfarin (Coumadin) * Intraoperative bladder injury or cystotomy * Physical or mental impairment that would affect the subject's ability to take medications daily or fill out questionnaires * Reported allergy to any of the ingredients in the cranberry, MH, or placebo pill
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Urinary Track Infection (UTI) | From surgery to one week post-op visit, approximately 1 week post surgery | Incidence of UTIs will be diagnosed at one week post-op visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 93 |
| 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. | 89 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Methenamine Hippurate With Cranberry | Placebo With Cranberry | Total |
|---|---|---|---|
| Age, Continuous | 61.27 years STANDARD_DEVIATION 12.86 | 60.61 years STANDARD_DEVIATION 12.44 | 60.95 years STANDARD_DEVIATION 12.63 |
| Race/Ethnicity, Customized African American | 6 participants | 4 participants | 10 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 85 participants | 85 participants | 170 participants |
| Region of Enrollment United States | 93 participants | 89 participants | 182 participants |
| Sex: Female, Male Female | 93 Participants | 89 Participants | 182 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 89 |
| other Total, other adverse events | 0 / 93 | 0 / 89 |
| serious Total, serious adverse events | 0 / 93 | 0 / 89 |
Outcome results
Primary
Incidence of Urinary Track Infection (UTI)
Incidence of UTIs will be diagnosed at one week post-op visit.
Time frame: From surgery to one week post-op visit, approximately 1 week post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methenamine Hippurate With Cranberry | Incidence of Urinary Track Infection (UTI) | 62 Participants |
| Placebo With Cranberry | Incidence of Urinary Track Infection (UTI) | 71 Participants |