Nitrofurantoin Prophylaxis During Catheter-managed Acute Urinary Retention After Pelvic Reconstructive Surgery
| Status: | Completed |
|---|---|
| Conditions: | Women's Studies, Urology |
| Therapuetic Areas: | Nephrology / Urology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/1/2018 |
| Start Date: | August 2016 |
| End Date: | May 12, 2018 |
A Randomized, Double-blind, Placebo-controlled Trial of Nitrofurantoin Prophylaxis During Catheterization for Acute Postoperative Urinary Retention After Pelvic Reconstructive Surgery
The specific aim of this randomized double-blind placebo-controlled trial is to determine if
extended release nitrofurantoin antibiotic prophylaxis decreases the incidence of symptomatic
urinary tract infection (UTI) compared with placebo for patients undergoing short term
indwelling or clean intermittent self-catheterization (CISC) for acute postoperative urinary
retention following pelvic organ prolapse and/or urinary incontinence surgery.
Consented patients who undergo urogenital surgery and fail their post-operative voiding trial
will be randomized to either extended release nitrofurantoin 100mg or an identical appearing
placebo capsule to be taken daily while performing CISC or while indwelling catheter is in
place. The primary outcome will be symptomatic and culture confirmed UTI within six weeks of
surgery. Secondary outcomes include adverse events associated with nitrofurantoin use, and
incidence of nitrofurantoin-resistant isolates from urine culture of symptomatic women.
Primary and secondary outcomes will be evaluated with Student t test and chi squared or
Fisher exact test as appropriate. Assuming a decrease in symptomatic UTIs attributable to
nitrofurantoin prophylaxis from 33% to 13%, with 80% power, and a two-sided alpha of 0.05,
and a 10% dropout rate, we should recruit a total of 154 patients.
extended release nitrofurantoin antibiotic prophylaxis decreases the incidence of symptomatic
urinary tract infection (UTI) compared with placebo for patients undergoing short term
indwelling or clean intermittent self-catheterization (CISC) for acute postoperative urinary
retention following pelvic organ prolapse and/or urinary incontinence surgery.
Consented patients who undergo urogenital surgery and fail their post-operative voiding trial
will be randomized to either extended release nitrofurantoin 100mg or an identical appearing
placebo capsule to be taken daily while performing CISC or while indwelling catheter is in
place. The primary outcome will be symptomatic and culture confirmed UTI within six weeks of
surgery. Secondary outcomes include adverse events associated with nitrofurantoin use, and
incidence of nitrofurantoin-resistant isolates from urine culture of symptomatic women.
Primary and secondary outcomes will be evaluated with Student t test and chi squared or
Fisher exact test as appropriate. Assuming a decrease in symptomatic UTIs attributable to
nitrofurantoin prophylaxis from 33% to 13%, with 80% power, and a two-sided alpha of 0.05,
and a 10% dropout rate, we should recruit a total of 154 patients.
Urinary tract infections (UTI) occur frequently following surgery for urinary incontinence or
pelvic organ prolapse (POP), with reported incidence up to 48%. This high rate is frequently
attributed to intraoperative factors, such as manipulation of the genitourinary tract and
instrumentation of the bladder and urethra, as well as an approximately 50% rate of short
term postoperative catheterization following urogynecologic surgery. As American women have a
20% lifetime risk of surgery for POP or urinary incontinence, the absolute number of women at
risk for urinary infectious morbidity associated with these procedures is quite high.
The substantial risk of UTI following POP or incontinence surgery, combined with the
well-established risk associated with catheterization, leads many practitioners to prescribe
oral antibiotics to women undergoing catheterization in the postoperative period. However,
there is minimal Level I evidence to support or refute this practice. The Infectious Disease
Society of America (IDSA) Guideline acknowledges that prophylactic antibiotics have been
shown to reduce UTI rates among patients using short term postoperative catheterization in
randomized trials. However, they recommend against routine antibiotic prophylaxis use due to
concerns regarding anti-microbial resistance, cost, and potential for adverse effects, even
among high risk groups including women undergoing urogynecologic surgery. This recommendation
is based on expert opinion, given a paucity of trial data to guide clinical care.
Nitrofurantoin is a commonly used antibiotic for UTI prophylaxis during catheterization, is
well-tolerated with few adverse effects, and is known to have a very low rate of associated
resistance. After decades of use, it remains active against the most common UTI pathogens
that have gained resistance to other antimicrobials. For example, in the 2013 Magee-Womens
Hospital Adult Antibiogram, 98% of E-coli specimens were sensitive to Nitrofurantoin, which
has been consistent since at least 2007. The drug has a half-life of 20 minutes and 40% is
concentrated in and excreted into the urine in a therapeutically unchanged form. Thus it has
minimal impact on vaginal and bowel flora. Nitrofurantoin has been shown to reduce the
incidence of positive urine cultures and symptomatic UTIs in women with a suprapubic catheter
after pelvic organ prolapse and/or urinary incontinence surgery. No trials have evaluated
nitrofurantoin prophylaxis for women using short term indwelling catheters or CISC following
urogynecologic procedures.
Given the large number of women at risk for urinary infectious morbidity associated with
short term catheterization for acute urinary retention following POP and/or incontinence
surgery, and the paucity of data on the impact of antibiotic prophylaxis in this setting, we
propose to demonstrate the efficacy of nitrofurantoin prophylaxis through an
adequately-powered, placebo-controlled trial. Secondary outcomes will include adverse events
associated with nitrofurantoin use, and incidence of nitrofurantoin resistant bacterial
isolates from urine culture.
Primary Aim: To determine if extended release nitrofurantoin administered daily to patients
using indwelling or clean intermittent self-catheterization (CISC) after pelvic organ
prolapse and/or urinary incontinence surgery will decrease the incidence of symptomatic and
culture proven urinary tract infection (UTI) when compared to placebo in a randomized,
double-blind trial.
Secondary Aim(s): To determine how nitrofurantoin antibiotic prophylaxis administered to
patients using an indwelling catheter or CISC after pelvic organ prolapse and/or urinary
incontinence surgery affects frequency of adverse events related to daily nitrofurantoin
exposure, and frequency of urine cultures positive for nitrofurantoin-resistant isolates.
The Null Hypotheses: Nitrofurantoin antibiotic prophylaxis administered to patients using an
indwelling catheter or CISC after pelvic organ prolapse and/or urinary incontinence surgery
does not change the incidence of symptomatic and culture proven urinary tract infection (UTI)
compared with placebo.
pelvic organ prolapse (POP), with reported incidence up to 48%. This high rate is frequently
attributed to intraoperative factors, such as manipulation of the genitourinary tract and
instrumentation of the bladder and urethra, as well as an approximately 50% rate of short
term postoperative catheterization following urogynecologic surgery. As American women have a
20% lifetime risk of surgery for POP or urinary incontinence, the absolute number of women at
risk for urinary infectious morbidity associated with these procedures is quite high.
The substantial risk of UTI following POP or incontinence surgery, combined with the
well-established risk associated with catheterization, leads many practitioners to prescribe
oral antibiotics to women undergoing catheterization in the postoperative period. However,
there is minimal Level I evidence to support or refute this practice. The Infectious Disease
Society of America (IDSA) Guideline acknowledges that prophylactic antibiotics have been
shown to reduce UTI rates among patients using short term postoperative catheterization in
randomized trials. However, they recommend against routine antibiotic prophylaxis use due to
concerns regarding anti-microbial resistance, cost, and potential for adverse effects, even
among high risk groups including women undergoing urogynecologic surgery. This recommendation
is based on expert opinion, given a paucity of trial data to guide clinical care.
Nitrofurantoin is a commonly used antibiotic for UTI prophylaxis during catheterization, is
well-tolerated with few adverse effects, and is known to have a very low rate of associated
resistance. After decades of use, it remains active against the most common UTI pathogens
that have gained resistance to other antimicrobials. For example, in the 2013 Magee-Womens
Hospital Adult Antibiogram, 98% of E-coli specimens were sensitive to Nitrofurantoin, which
has been consistent since at least 2007. The drug has a half-life of 20 minutes and 40% is
concentrated in and excreted into the urine in a therapeutically unchanged form. Thus it has
minimal impact on vaginal and bowel flora. Nitrofurantoin has been shown to reduce the
incidence of positive urine cultures and symptomatic UTIs in women with a suprapubic catheter
after pelvic organ prolapse and/or urinary incontinence surgery. No trials have evaluated
nitrofurantoin prophylaxis for women using short term indwelling catheters or CISC following
urogynecologic procedures.
Given the large number of women at risk for urinary infectious morbidity associated with
short term catheterization for acute urinary retention following POP and/or incontinence
surgery, and the paucity of data on the impact of antibiotic prophylaxis in this setting, we
propose to demonstrate the efficacy of nitrofurantoin prophylaxis through an
adequately-powered, placebo-controlled trial. Secondary outcomes will include adverse events
associated with nitrofurantoin use, and incidence of nitrofurantoin resistant bacterial
isolates from urine culture.
Primary Aim: To determine if extended release nitrofurantoin administered daily to patients
using indwelling or clean intermittent self-catheterization (CISC) after pelvic organ
prolapse and/or urinary incontinence surgery will decrease the incidence of symptomatic and
culture proven urinary tract infection (UTI) when compared to placebo in a randomized,
double-blind trial.
Secondary Aim(s): To determine how nitrofurantoin antibiotic prophylaxis administered to
patients using an indwelling catheter or CISC after pelvic organ prolapse and/or urinary
incontinence surgery affects frequency of adverse events related to daily nitrofurantoin
exposure, and frequency of urine cultures positive for nitrofurantoin-resistant isolates.
The Null Hypotheses: Nitrofurantoin antibiotic prophylaxis administered to patients using an
indwelling catheter or CISC after pelvic organ prolapse and/or urinary incontinence surgery
does not change the incidence of symptomatic and culture proven urinary tract infection (UTI)
compared with placebo.
Inclusion Criteria:
- Women who have undergone surgery for the correction of pelvic organ prolapse and/or
urinary incontinence and failed a postoperative voiding trial
Exclusion Criteria:
- Known drug allergy to nitrofurantoin
- History of renal insufficiency
- Renal transplant
- Renal nephropathy
- Recent history of more than 3 UTIs per year
- History of nitrofurantoin-induced pulmonary injury or nitrofurantoin associated
cholestatic jaundice/hepatic dysfunction
- Known immunocompromised condition (organ transplant, chemotherapy, immune suppression
associated with autoimmune disease).
We found this trial at
2
sites
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300 Halket St.
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
1-866-MyMagee (696-2433)
Magee-Womens Hospital of UPMC Magee-Womens Hospital of UPMC is a world-class center for both women's...
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