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NAUTICA: Nitrofurantoin Administration for the Prevention of Short-Term Catheter Associated Urinary Tract Infection After Pelvic Surgery

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Completed
CT.gov ID
NCT03287089
Collaborator
(none)
164
Enrollment
1
Location
2
Arms
20
Actual Duration (Months)
8.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The specific aim of this randomized double-blind placebo-controlled trial is to evaluate the efficacy of administration of nitrofurantoin prophylaxis after catheter discontinuation for the prevention of catheter-associated urinary tract infections in patients with postoperative short-term catheterization following pelvic reconstructive surgery and/or urinary incontinence surgery.

Patients that undergo pelvic organ prolapse and/or urinary incontinence surgery and fail their post-operative voiding trial will be included in the study. Upon successfully passing and in-office voiding trial at the time of catheter removal, they will be randomized to either nitrofurantoin 100mg twice daily or an identical appearing placebo capsule twice daily for 5 days following catheter removal. The primary outcome will be the treatment of clinically suspected and/or culture-proven UTI within 30 days of surgery. Secondary outcomes include adverse events associated with nitrofurantoin use and medication compliance.

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 32% to 14%, with 80% power, and a two-sided alpha of 0.05, we should recruit a total of 164 patients.

Condition or Disease Intervention/Treatment Phase
  • Drug: Nitrofurantoin 100 MG
  • Drug: Placebo Oral Tablet
 Phase 4

Detailed Description

Urinary tract infections (UTI) are the most common hospital-acquired infections, accounting for nearly 30% of cases of nosocomial infections and affecting nearly 1 million people per year.

Following pelvic reconstructive and urinary incontinence surgery, UTIs are one of the most common complications with a risk between 8.9%-34%. The baseline risk of UTI associated with pelvic floor surgery ranges between 5-35%, increasing greatly with catheterization.

Postoperative voiding dysfunction and incomplete bladder emptying is common following pelvic reconstructive and incontinence surgeries, with incidence ranging from 2.5 % to 31%. As a result, these women may have additional catheterization for a short period of time, which increases the risk of UTI. There is a 15-20% risk of developing a postoperative UTI with short-term catheterization, even if the catheter remains in place for merely 24 hours. The risk of UTI increases 5-10% each day the catheter is left in place.

Numerous studies have been conducted to evaluate different prophylactic antibiotic regimens to help decrease the rate of postoperative catheter-associated UTIs. Many of these studies have shown precedent for the use of antibiotic prophylaxis.

Nitrofurantoin has been evaluated as a prophylactic regimen for use during short-term catheterization. These studies had favorable results, decreasing the incidence of UTI postoperatively.

Although there are a few studies showing favorable results for the use of prophylactic nitrofurantoin during catheterization after pelvic surgery, the optimal timing of antibiotic administration and length of dosing regimen is not well defined. The American Urological Association (AUA) recommends empiric antibiotic treatment at the time of external urinary catheter removal in patients with risk factors, such as tobacco use, advanced age, and anatomic abnormalities of the urinary tract. The AUA Panel does cite that bacteriuria in the setting of noninfectious urinary tract disease is a risk factor for bacteremia, and, thus, prophylactic antibiotic treatment at time the of catheter removal may be indicated. The AUA does recommend empiric antibiotic treatment at the removal of an external urinary catheter in patients with risk factors. However, there is no standardization concerning the type of antibiotic to be used or treatment duration.

Although there are a few studies showing favorable results for use of nitrofurantoin during catheterization after pelvic surgery, there are no clearly defined recommendations regarding its use for urinary tract infection prevention after catheter removal. Therefore, the objective of our study is to examine the effects of administration of nitrofurantoin therapy at the time of Foley catheter removal for the prevention of catheter-associated UTI in patients undergoing POP and/or urinary incontinence surgery.

Primary Objective:

To evaluate the efficacy of administration of nitrofurantoin prophylaxis after catheter discontinuation for the prevention of catheter-associated urinary tract infections in patients with postoperative short-term catheterization following pelvic reconstructive surgery. The primary outcome will be the treatment of clinically suspected and/or culture-proven UTI within 30 days of surgery.

Secondary Objective:

To evaluate adverse outcomes related to study medications in each group and to evaluate medication compliance

Null Hypothesis:

The null hypothesis is that the administration of nitrofurantoin will not reduce the rate of UTI compared with placebo.

Study Design

Study Type:
Interventional
Actual Enrollment :
164 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Nitrofurantoin Administration for the Prevention of Short-Term Catheter Associated Urinary Tract Infection After Pelvic Surgery (NAUTICA): A Randomized Controlled Trial
Actual Study Start Date :
Sep 29, 2017
Actual Primary Completion Date :
May 30, 2019
Actual Study Completion Date :
Jun 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Nitrofurantoin

Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal

Drug: Nitrofurantoin 100 MG
Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days
Placebo Comparator: Placebo

Receives twice daily matching placebo for 5 days following catheter removal

Drug: Placebo Oral Tablet
Matching placebo

Outcome Measures

Primary Outcome Measures

  1. UTI [within 30 days of surgery]

    Number of participants with a urinary tract infection in the first 30 days following pelvic reconstructive surgery

Secondary Outcome Measures

  1. Adverse Events [within 30 days of surgery]

    Number of participants with an adverse event only related to study drug administration

  2. Medication Compliance [within 30 days of surgery]

    Compliance assessed by use of a medication diary during treatment period

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Age greater than 18

  • Creatinine clearance greater than 30 ml/min

  • Failed postoperative hospital voiding trial

Exclusion Criteria:

  • Pregnant

  • History of glucose-6-phosphate dehydrogenase deficiency

  • History of renal insufficiency, renal transplant, or nephropathy

  • Allergy to nitrofurantoin

  • History of recurrent UTI (defined as greater than two culture-proven infections in six months or three infections in one year)

  • Urinary Tract Infection (UTI) within 14 days one month of surgery

  • Non-English speaking

  • Urinary tract infection while Foley catheter is in place

  • On antibiotic therapy for other non-urological reasons

  • Sustained intraoperative bladder injury requiring prolonged catheterization greater than 5 days

  • Undergoing mesh excision from within the bladder, fistula repair, cystotomy repair, urethral diverticulectomy, sacral neuromodulation, urethral surgery, or any other procedure requiring prolonged catheterization and bladder decompression

  • Placement of a suprapubic catheter

  • Participants that request intermittent self-catheterization

  • Neurologic conditions affecting urinary tract system and normal voiding mechanisms

  • History of hepatic impairment due to prior nitrofurantoin use

  • Inability to provide consent/decisionally impaired

  • More than two in-office voiding trials

Contacts and Locations

Locations

Site City State Country Postal Code
1 Atrium Health Charlotte North Carolina United States 28207

Sponsors and Collaborators

  • Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Dina Bastawros, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:
NCT03287089
Other Study ID Numbers:
  • Pro00022622
First Posted:
Sep 19, 2017
Last Update Posted:
Aug 9, 2022
Last Verified:
May 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Wake Forest University Health Sciences
Nitrofurantoin
Prolapse
Pelvic Organ Prolapse
Anti-incontinence procedure
Urinary retention
Urinary Tract Infection
Short-term catheterization
Additional relevant MeSH terms:
Infections
Communicable Diseases
Urinary Tract Infections
Nitrofurantoin

Study Results

Participant Flow

Recruitment Details Consecutive women were prescreened for eligibility and introduced to the study prior to surgery. Women with postoperative urinary retention following pelvic organ prolapse and/or incontinence surgery were approached for study inclusion at the time of their postoperative in-office voiding trial between September 2017 and April 2019.
Pre-assignment Detail Women were deemed as "enrolled" once they consented and randomized. No enrolled participants were excluded with this definition.
Arm/Group Title Nitrofurantoin Placebo
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo
Period Title: Overall Study
STARTED 82 82
COMPLETED 82 76
NOT COMPLETED 0 6

Baseline Characteristics

Arm/Group Title Nitrofurantoin Placebo Total
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo Total of all reporting groups
Overall Participants 82 82 164
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
61.6
(11.7)
61.1
(12.4)
61.4
(12.0)
Sex/Gender, Customized (Count of Participants)
Female
82
100%
82
100%
164
100%
Male
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian
79
96.3%
72
87.8%
151
92.1%
Black
1
1.2%
8
9.8%
9
5.5%
Other
2
2.4%
2
2.4%
4
2.4%
Body Mass Index (BMI), kg/m^2 (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
27.1
(4.7)
28.6
(5)
27.8
(4.9)
Parity (Parity) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Parity]
2
2
2
POP-Q Stage (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]
2
2
2
Menopausal Status (Count of Participants)
Premenopausal
18
22%
17
20.7%
35
21.3%
Postmenopausal
64
78%
64
78%
128
78%
Missing data
0
0%
1
1.2%
1
0.6%
Postmenopausal Hormone Use (Count of Participants)
No Hormone Therapy
58
70.7%
58
70.7%
116
70.7%
Vaginal Estrogen Therapy
20
24.4%
19
23.2%
39
23.8%
Systemic Hormonal Therapy
4
4.9%
5
6.1%
9
5.5%
Current Smoking (Count of Participants)
Count of Participants [Participants]
6
7.3%
6
7.3%
12
7.3%
History of Recurrent UTI (Count of Participants)
Count of Participants [Participants]
1
1.2%
1
1.2%
2
1.2%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]
9
11%
10
12.2%
19
11.6%
Preoperative PVR Volume (mL) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]
57.9
(92.6)
45.3
(55.7)
51.4
(75.5)
Creatinine Clearance (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]
84.1
(30.1)
94.2
(34.9)
89.1
(32.9)
Type of Procedure (Count of Participants)
Mid urethral sling surgery
50
61%
47
57.3%
97
59.1%
Burch colposuspension
1
1.2%
2
2.4%
3
1.8%
Anterior repair
15
18.3%
20
24.4%
35
21.3%
Posterior repair
53
64.6%
59
72%
112
68.3%
Hysterectomy
32
39%
35
42.7%
67
40.9%
Vaginectomy/colpocleisis
7
8.5%
2
2.4%
9
5.5%
Uterosacral ligament suspension
18
22%
24
29.3%
42
25.6%
Sacrospinous ligament fixation
0
0%
1
1.2%
1
0.6%
Iliococcygeus vault suspension
1
1.2%
1
1.2%
2
1.2%
Sacral colpopexy
4
4.9%
1
1.2%
5
3%
Vaginal mesh excision
4
4.9%
1
1.2%
5
3%
Operative Time (mins) (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]
134
(80.8)
142.9
(86.9)
138.4
(83.8)
Estimated Blood Loss (mL) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]
45.5
(35.5)
60.9
(61.6)
53.2
(50.7)
Length of Hospital Stay (days) (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]
1
1
1
Duration of Catheterization (days) (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]
3
3
3

Outcome Measures

1. Primary Outcome
Title UTI
Description Number of participants with a urinary tract infection in the first 30 days following pelvic reconstructive surgery
Time Frame within 30 days of surgery

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Nitrofurantoin Placebo
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo
Measure Participants 82 82
Count of Participants [Participants]
15
18.3%
14
17.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitrofurantoin, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.84
Comments
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.49 to 2.43
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Adverse Events
Description Number of participants with an adverse event only related to study drug administration
Time Frame within 30 days of surgery

Outcome Measure Data

Analysis Population Description
This is the total number of participants with an allergy or intolerance to the study medication.These adverse symptoms included: hives, pruritus, rash, anaphylaxis, nausea, vomiting, diarrhea, and other.
Arm/Group Title Nitrofurantoin Placebo
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo
Measure Participants 5 4
Allergy
0
0%
0
0%
Nausea
5
6.1%
2
2.4%
Vomiting
0
0%
0
0%
Diarrhea
0
0%
0
0%
Other
0
0%
2
2.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitrofurantoin, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method Chi-squared
Comments
3. Secondary Outcome
Title Medication Compliance
Description Compliance assessed by use of a medication diary during treatment period
Time Frame within 30 days of surgery

Outcome Measure Data

Analysis Population Description
Compliance was defined as the number pills taken divided by total number of pills dispensed (10). The closer this ratio is to "1" the better the compliance. The closer the ratio is to "0" the worse the compliance
Arm/Group Title Nitrofurantoin Placebo
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo
Measure Participants 82 82
Mean (Standard Deviation) [ratio]
0.95
(0.18)
0.96
(0.15)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitrofurantoin, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.68
Comments
Method t-test, 1 sided
Comments

Adverse Events

Time Frame 30 days (from surgery until 30 days postop)
Adverse Event Reporting Description Adverse events data related to study medication was collected (i.e. allergies and/or intolerances)
Arm/Group Title Nitrofurantoin Placebo
Arm/Group Description Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal Nitrofurantoin 100 MG: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days Receives twice daily matching placebo for 5 days following catheter removal Placebo Oral Tablet: Matching placebo
All Cause Mortality
Nitrofurantoin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/82 (0%) 0/82 (0%)
Serious Adverse Events
Nitrofurantoin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/82 (0%) 0/82 (0%)
Other (Not Including Serious) Adverse Events
Nitrofurantoin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/82 (6.1%) 4/82 (4.9%)
Gastrointestinal disorders
Medication Intolerance 5/82 (6.1%) 5 2/82 (2.4%) 2
General disorders
Medication Intolerance 0/82 (0%) 0 1/82 (1.2%) 1
Musculoskeletal and connective tissue disorders
Medication Intolerance 0/82 (0%) 0 1/82 (1.2%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dina Bastawros, MD
Organization Atrium Health
Phone 336-718-1970
Email dina.bastawros@gmail.com
Responsible Party:
Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:
NCT03287089
Other Study ID Numbers:
  • Pro00022622
First Posted:
Sep 19, 2017
Last Update Posted:
Aug 9, 2022
Last Verified:
May 1, 2020