Clinical trial NCT03287089
Conditions: Catheter-Associated Urinary Tract Infection
Keywords: Nitrofurantoin Prolapse Pelvic Organ Prolapse Anti-incontinence procedure Urinary retention Urinary Tract Infection Short-term catheterization
Sponsor: Wake Forest University Health Sciences
Start date: 2017-09-29; Completion date: 2019-06-01
Enrollment: 164 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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.

Arms: arm 1: Receives twice daily 100mg nitrofurantoin for 5 days following catheter removal arm 2: Receives twice daily matching placebo for 5 days following catheter removal
Interventions: intervention 1: Nitrofurantoin 100 MG intervention 2: Placebo Oral Tablet
Intervention descriptions: intervention 1: Patients will receive nitrofurantoin 100mg twice daily by mouth for 5 days intervention 2: Matching placebo

Protocol documents:
Prot_SAP_000.pdf: 
Study Title: Nitrofurantoin Administration for the Prevention of Short-Term Catheter 
Associated Urinary Tract Infection After Pelvic Surgery (NAUTICA): A Randomized Controlled 
Trial 
 
 
 
 
ClinicalTrials.gov ID: NCT03287089 
 
 
 
 
 
Date: July 6, 2018 
 
 


STUDY OBJECTIVES 
 
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 Objectives 
 
1. To evaluate adverse outcomes related to study medications in each group  
2. To evaluate medication compliance 
 
BACKGROUND 
 
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.1-3 They account for nearly 8.1 million visits to health care 
providers and cost an estimated $1.6 billion a year in the United States alone.3,4  
 
Following pelvic reconstructive and urinary incontinence surgery, UTIs are one of the 
most common complications.4,5 The baseline risk of UTI associated with pelvic floor 
surgery ranges between 5-35%, increasing greatly with catheterization.3 In women who 
are undergoing surgery for urinary incontinence, the risk of UTI ranges between 8.9% to 
34%.4,6,7 Risk factors for urinary tract infections in women undergoing pelvic floor and 
urinary incontinence surgery include: history of recurrent UTI, longer operative times, 
and increased duration of postoperative catheterization.6 
Postoperative voiding dysfunction and incomplete bladder emptying is common 
following pelvic reconstructive and incontinence surgeries, with incidence ranging from  
2.5 % to 31%.6 As a result, these women may have additional catheterization for a short 
period of time, which increases the risk of UTI.1,2,4,5 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.8 The risk of UTI increases 5-10% each day the catheter is left 
in place.1 In the SISTEr trial, which was a multicenter, prospective, randomized trial 
comparing Burch colposuspension versus autologous fascial slings for the treatment of 
stress urinary incontinence, catheter usage postoperatively for incomplete bladder 
emptying resulted in an increased rate of UTIs. Participants who underwent the fascial 
sling (48%) had more UTI events (305) compared with the 32% of women in the Burch 
colposuspension group (203) (p<0.001).9   


This was concluded to be secondary to the prolonged need for catheterization due to 
postoperative voiding dysfunction.5,9,10  
 
Complications of catheter-associated UTI can include pyelonephritis, renal disease, and 
bacteremia.2,5 These complications increase the morbidity of the patients undergoing 
these surgeries, especially in those who are elderly. The number of pelvic floor and 
urinary incontinence surgeries is expected to increase by 40% in the coming years; thus, 
it is imperative to target efforts to reduce the risk of postoperative UTI and its 
complications in the elderly population.3,5 
 
Numerous studies have been conducted to evaluate different prophylactic antibiotic 
regimens to help decrease the rate of postoperative catheter-associated UTIs.11 Many of 
these studies have shown precedent for the use of antibiotic prophylaxis.1,4,12 In a 
randomized, double-blind, placebo controlled trial by Van der Wall et al., they reported 
on the efficacy of ciprofloxacin in preventing UTI in short-term catheterization following 
surgery.1 In their study,  20% of placebo patients had symptomatic UTIs, compared with 
5% UTI rate in the ciprofloxacin treated group.1 Ghezzi et al. also demonstrated 
favorable results using single dose prulifloxacin to reduce the rate of UTI in women with 
short-term postoperative catheterization after undergoing a transvaginal tape 
procedure.2 In this prospective trial, no women in the prulifloxacin treatment group  had 
a positive urine culture (p<0.0001), symptomatic UTI at catheter removal (p = 0.0015) or 
a positive urine culture at 1 week follow-up (p =0.2).2 
 
In addition to fluoroquinolones, nitrofurantoin has also been evaluated as a prophylactic 
regimen for use with short-term catheterization. In her prospective, multicenter 
randomized controlled trial, Rogers et al. demonstrated that the daily use of 
nitrofurantoin crystals decreased risk of UTI in patients undergoing pelvic organ 
prolapse (POP) or urinary incontinence surgery when compared with placebo in those 
patients who had an indwelling suprapubic catheter postoperatively (46% versus 61%, 
p=0.002).12 Jackson et al. echoed these findings and found that a short 3-day course of 
nitrofurantoin twice daily after outpatient mid urethral sling surgery also significantly 
reduced the incidence of UTI in the first 6 weeks postoperatively in patients who were 
discharged with short-term catheterization (placebo 32% versus 17.6% in the 
nitrofurantoin group, p=0.04).4 Conversely, Dieter et al. found that prophylactic once 
daily nitrofurantoin during catheterization did not decrease the risk of urinary tract 
infection in patients receiving short-term catheterization following POP or urinary 
incontinence surgery.3  This finding was thought to be secondary to differences in study 
design lending to a lower baseline prevalence of UTI.3 Additionally, a Cochrane review of 
antibiotic prophylaxis for short-term catheter bladder drainage does find that there is 
some evidence, although limited, that the rate of bacteriuria is decreased with the 
administration of antimicrobials within the first postoperative days, or from 
postoperative day two until the catheter is removed.15  
 


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.13 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.13  This recommendation is based on a few studies providing 
evidence for antibiotic treatment at the time of catheter removal. One of these studies, 
a randomized controlled trial by Harding et al., studied women with asymptomatic 
catheter-acquired bacteriuria after short-term catheterization and randomly assigned 
them to receive antibiotic therapy or no therapy at the time of Foley catheter removal. 
All women had urine cultures collected for up to 14 to 28 days following catheter 
removal. Those with antibiotic therapy demonstrated a significant increase in 
elimination of bacteriuria (81%) with oral antibiotics compared to the untreated 
population (36%).14 Based on these studies, the AUA does recommend empiric antibiotic 
treatment at the removal of an external urinary catheter in patients with risk factors.13 
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 
doing 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.  
 
STUDY DESIGN AND METHODS 
 
This is a randomized, double-blind, placebo-controlled trial offered to patients who 
receive postoperative short-term transurethral catheterization after undergoing surgery 
for pelvic organ prolapse (POP), urinary incontinence, or both. The study will be 
conducted at two clinical sites: 
 
1. Women’s Center for Pelvic Health (Mercy), Atrium Health, Charlotte, NC 
2. Women’s Center for Pelvic Health (NorthEast) Atrium Health, Concord, NC 
 
 
Human Subject Research and Informed Consent 
 
Each participant will be required to sign an Internal Review Board (IRB) approved 
consent at the time of enrollment prior to any study-related interventions or 


assessments. The informed consent form will describe the study in detail. Additionally, 
the study consent form will disclose the planned uses of study data, as well as potential 
risks to the participants. Each prospective subject will have the objectives of the study 
explained to them prior to enrollment. The subject will be given an opportunity to ask 
questions and decide whether or not to participate. Copies of the informed consent will 
be provided to the participants on request, and the originals will be stored at the 
primary study center (#1).  
 
Subjects have the right to: 
 Voluntarily participate in the study 
 Withdraw or refuse participation in the study at any point without questioning 
 Understand the objectives of the study 
 Understand the risks and benefits of the study 
 Have their confidentiality maintained 
Participant Screening and Point of Enrollment 
Participants scheduled to undergo surgery for pelvic organ prolapse (POP) or urinary 
incontinence will be identified and will be screened against inclusion and exclusion 
criteria. If confirmed to meet the requirements for the study, they will be eligible to be 
invited to participate in the study. Participants will be enrolled in the study once 
informed consent is obtained. 
Participants will be enrolled by physicians, fellows, nurse practitioners, physician’s 
assistants, and/or a research nurse prior to surgery. Each practitioner will receive 
education and training regarding the study enrollment.  
STUDY POPULATION 
Inclusion Criteria 
The study will include women who are seeking surgical management for POP or urinary 
incontinence.  
1. Age greater than 18 
2. Creatinine clearance greater than 30 ml/min 
3. Failed postoperative hospital voiding trial 
Exclusion Criteria 
1. Pregnant 
2. History of glucose-6-phosphate dehydrogenase deficiency 
3. History of renal insufficiency, renal transplant, or nephropathy 
4. Allergy to nitrofurantoin 


5. History of recurrent UTI (defined as greater than two culture-proven infections in 
six months or three infections in one year) 
6. Urinary Tract Infection (UTI) within one month of surgery  
7. Non-English speaking 
8. Urinary tract infection while Foley catheter is in place 
9. On antibiotic therapy for other non-urological reasons 
10. Sustained intraoperative bladder injury requiring prolonged catheterization 
greater than 5 days 
11. 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 
12. Placement of a suprapubic catheter 
13. Participants that request intermittent self-catheterization 
14. Neurologic conditions affecting urinary tract system and normal voiding 
mechanisms 
15. History of hepatic impairment due to prior nitrofurantoin use 
16. Inability to provide consent/decisionally impaired 
17. More than two in-office voiding trials 
Rationale for Nitrofurantoin and Regimen Chosen for This Protocol 
Nitrofurantoin was chosen as the interventional medication for this study due to its 
efficacy in reducing urinary tract infections in women that required short-term 
postoperative catheterization.4,12 Both prophylactic dosing (once daily) and therapeutic 
dosing (twice a day) have been studied. There are conflicting outcomes with once daily 
dosing, as one studied showed a decrease in UTI rates, while another did not when 
given during the catheterization time period.3,12 There is one study that showed a 
significant reduction in rate of UTI with twice daily dosing.4 Therefore, we have decided 
to proceed with twice daily dosing to ensure maximum coverage for UTI. 
Additionally, Escherichia coli, the most common uropathogen, displays low resistance 
patterns to nitrofurantoin in our geographical region.16 Trimethoprim-sulfamethoxazole 
(TMP-SMX), another first line therapy for treatment of UTI, which was the agent studied 
in a prior randomized controlled trial15, displays only a 75% sensitivity for treating 
Escherichia coli in our hospital system.16 Conversely, nitrofurantoin has a 98% sensitivity 
for treating Escherichia coli in our hospital system.16 
In this study, not all of the participants will be receiving antibiotic treatment during the 
study course. Per the 2009 International Clinical Practice Guidelines from the Infectious 
Diseases Society of America (IDSA), prophylactic antimicrobials should not be routinely 
used in patients with indwelling catheterization due to the concern about selection of 
antimicrobial resistance. However, they cite that additional studies must be undertaken, 
given the findings of previous research that does illustrate fewer UTIs in patients who 


receive antimicrobial prophylaxis at the time of catheter removal.17 The data is still 
evolving regarding prophylactic antimicrobials. We are also limiting the exposure to the 
antibiotic treatment to only 5 days; recommended treatment courses for nitrofurantoin 
range from 5-7 days.21,22  
Study Withdrawal 
Participants may withdraw from the study at any point in time. Documentation of the 
reason for withdrawal will be captured in the data collection forms. There will be no risk 
to participants that choose to withdraw from the study. 
Preoperative Period 
All consecutive participants undergoing a scheduled surgery for POP and/or urinary 
incontinence will be identified, screened, and approached for enrollment. All will be 
screened for UTI. To be eligible to participate, the participant is not to have a UTI from 1 
day to 1 month prior to surgery. Participants will be asked if they have any dysuria, 
frequency, or bladder irritation in the absence of vaginal discharge. A “YES” to all three 
of these symptoms indicates a positive screen, and therefore, the participant will be 
excluded. Additionally, the participant with be asked if they have been treated for a UTI 
within the past month with antibiotics. A “YES” indicates a positive screen, and 
therefore, the participant will be excluded. 
Participants who do not meet the inclusion and exclusion criteria will be considered 
screen failures. Screen failures will be captured and the cause for screen failure will be 
documented. 
Perioperative and Surgery Period 
All participants will receive routine preoperative intravenous antibiotic prophylaxis 
based on standard hospital protocols. This will either be 2 or 3 grams of cefazolin based 
on patient weight. In the event of an allergy, an appropriate alternative, such as 
clindamycin 900 milligrams plus aztreonam 2 grams, will be given. All participants will 
have a 16 French latex Foley catheter placed intraoperatively using sterile technique. 
Any patient with a latex allergy will receive a non-latex 16 French Foley catheter. 
Postoperative Period 
All participants will undergo a postoperative retrograde fill voiding trial per our 
division’s standard protocol on postoperative day zero prior to discharge (for outpatient 
procedures) or on the morning of postoperative day 1 for hospitalized participants.  
 
Participants will pass the voiding trial if they void more than 200 mL with less than one-
third post-void residual. If they fail, a 16 French Foley catheter will be reinserted.  


 
All participants that fail the voiding trial will be discharged home with an indwelling 
Foley catheter. These participants will receive Foley maintenance education prior to 
discharge. They will be scheduled for a follow up voiding trial in the office in 1-7 days. 
The names of all participants that fail the voiding trial will be communicated to the 
principal investigator and/or the research nurse for continued follow up. 
In Office Voiding Trial 
Participants who are discharged with an indwelling Foley catheter will be scheduled to 
return to the office in 1-7 days for an in-office retrograde voiding trial. All office 
personnel (nurses, medical assistants, physicians, physician’s assistants, and nurse 
practitioners) will receive education regarding voiding trial technique as outlined below 
prior to study commencement. 
 
The bladder will be retrograde filled with normal saline up to a maximum of 300mL, and 
the catheter will then be removed. The participant will attempt to void immediately, but 
the participant will have up to 60 minutes to attempt voiding. After voiding, the 
participant will be asked to complete a Force of Stream questionnaire.17 The urine will 
be measured and a post-void residual will be obtained with a bladder scan. If urine 
voided is 200 mL or greater, and the post-void residual is less than one-third of the total 
amount (voided volume plus residual volume), the catheter will be left out and the 
participant will be considered a voiding trial pass. If the volume is less than 200 mL, and 
the post-void residual is greater than one third of the total amount, the participant will 
be deemed a voiding trial failure; these patients will be sent home with a Foley catheter.  
After completing a bladder scan immediately after voiding attempt, the provider will be 
notified of the voided volume and post-void residual (to be obtained by bladder scan). 
 
Once a participant has successfully passed the voiding trial, they will be eligible for 
randomization.  
Randomization 
Randomization will be controlled by the Carolinas HealthCare System Investigational 
Drug Services pharmacy through random permuted blocks and stratified per site. The 
biostatistician will generate the randomization sequence and provide this information to 
the pharmacist. 
The study will be double-blinded such that both study participants and investigators will 
be masked to treatment allocation and block size randomization, except for the 
pharmacist and statistician, who will have no contact with the patients.  
The Investigational Drug Services (IDS) pharmacy will provided blinded medication 
bottles containing either nitrofurantoin or placebo 100mg capsules. Each bottle will 


contain 10 capsules. These bottles will be labeled by the IDS pharmacy with a 
randomization number. The study medications will be released by the pharmacy to the 
research nurse, who is also blinded. The medication bottles will be stored in a locked 
cabinet in a climate-controlled room until dispensed.  
Eligible participants that have successfully passed the in-office voiding trial will be 
randomized into one of two groups upon completion of the voiding trial data collection 
sheet. There will be no indication which group the participant was randomized to. These 
sheets will be fluorescent colored and a part of each participant’s chart. This sheet will 
need to be completed by the nurse administering the voiding trial.  
 
The participants randomized to Group A will receive 100 mg nitrofurantoin every 12 
hours by mouth starting on the day the Foley catheter is removed and complete a five-
day course. Conversely, participants randomized into Group B will receive a matched 
placebo every 12 hours each day starting on the date of Foley catheter removal, for five 
days. Again, there will be no indication which group the participant was randomized to. 
 
At the time of randomization, the participant will be assigned a randomization number. 
The bottle of medication with the same corresponding randomization ID will be 
dispensed. This will be a bottle of 10 capsules of nitrofurantoin or matching placebo 
with instructions to take every 12 hours for five days. The first dose will be given in the 
office. Participants will be asked to complete a one-week medication diary.  Participants 
will be asked to return this bottle of medication, any unused medication, and a 
medication compliance diary at the first postoperative visit following surgery.   
Any participant that fails the in-office voiding trial will be treated per standard clinical 
practice. That participant will be scheduled to return for an additional in-office voiding 
trial in 1-7 days. They will still be eligible to participate in the study after a passed 
voiding trial in the office. Data will still be collected on these participants. If the 
participant elects to intermittent self-catheterize, they will then be excluded from the 
study. Any participant that required any more than two in-office voiding trials 
postoperatively will be excluded. 
Week 2 Postoperative Visit (+/- 1 week) 
Participants will be scheduled for a 2-week postoperative follow up visit. They will be 
instructed to return their bottle of study medication and a medication compliance diary 
at this visit. 
 
 
 


Treatment of UTIs 
 
Urinary tract infection will be defined as: 
 Any treatment received (outside of study drug) for clinically suspected UTI 
and/or a culture-proven UTI with a uropathogen within the first 30 days 
following surgery.  
o A urine culture is deemed positive if there are greater than 100,000 
colony-forming units of a single organism. Urine cultures with mixed 
bacterial flora will NOT be classified as a positive culture. 
o Clinically suspected UTIs will be defined as dysuria, frequency, and 
irritation in the absence of vaginal discharge.  
Study participants will not be eligible to take phenazopyridine while on study 
medications.  
If a participant has clinical symptoms of a UTI during the study period, a urine specimen 
will be sent for culture and treatment will be based on appropriate antibiotics regarding 
specific susceptibilities. Per the IDSA guidelines, the following duration of treatment 
guidelines will be followed18: 
 7-14 days duration of antimicrobial treatment for patients with a catheter-
associated UTI, regardless of whether the catheter is in place or not 
 A 3-day antimicrobial regimen may be considered for women aged 65 years old 
or less who develop a catheter-associated UTI after the catheter has been 
removed 
 
The investigator will maintain discretion to deviate from these guidelines pending 
clinical reasons. 
 
The participant will be treated empirically for seven days with one of the following 
antibiotics while awaiting urine culture results, based on personal treatment history, 
contraindications, and allergies17: 
 Cephalexin (500mg every 12 hours for 7-14 days) by mouth OR 
 Fosfomycin (3 grams once) by mouth OR 
 Ciprofloxacin (250 mg every 12 hours for 3 days OR 250-500mg every 12 hours 
for 7-14 days) by mouth 
 
Fosfomycin is a single dose regimen. Although the IDSA recommends a 3-day or 7-14 
day treatment course, recent in-vitro studies indicate that a single dose of fosfomycin is 
also effective and cost effective.19,20 Fosfomycin was demonstrated to have high 
bactericidal activity against biofilms on siliconized latex catheters.19 Therefore, it will 
also be offered as a treatment option for UTI to our participants. 
 


Urine cultures will be obtained with susceptibilities, and antibiotic treatment may be 
changed depending on resistance. Once the uropathogen is known, the appropriate 
antibiotic regimen to treat the known uropathogen will employed.  
 
If a participant is being empirically treated for a UTI, and the urine culture returns 
negative, the participant will be notified and instructed to stop taking the antibiotics. 
 
The triage nursing staff, both in office and through the nursing phone triage service will 
receive study training prior to study commencement.  Any participant that contacts our 
office outside of normal business hours with concerns of a UTI will be triaged and 
empirically treated with one of the appropriate antibiotics listed above. If they receive 
treatment from another provider outside our hospital system, authorization for release 
of records will be need to be signed by the participant.  
 
Any participant that has a positive urine culture from an outside provider, or is treated 
based on clinical symptoms without evidence of a positive urine culture will be deemed 
a treatment failure. These participants will be included in the study analysis as 
treatment failures. 
DATA COLLECTION AND MANAGEMENT 
All study data will be recorded by research staff and securely maintained at primary site.  
Data will be entered by study staff into REDCap database that will be stored on a secure 
server.  
Each patient will have a unique identification number to which only the principal and co-
investigators will have access. The data collection spreadsheet will not contain any 
patient identifiers and will be password protected. The master list that links the patients 
and their study identification number will be stored separately from the database. All 
collected information will be stored separately on a password protected hard drive. A 
back up copy of the file will be stored on a password protected hospital network 
drive.  All hard copies of study data will be stored in a locked cabinet in the office of the 
research nurse, which will also be locked. 
 
 
 
 
 


 
OUTCOME MEASURES 
Primary Hypothesis 
The primary hypothesis is that the administration of nitrofurantoin will reduce the UTI 
rate compared to the UTI rate in the placebo arm upon discontinuation of 
catheterization. The null hypothesis is that the administration of nitrofurantoin will not 
reduce the rate of UTI. 
Primary Outcome Measure 
The primary outcome of the study will be the treatment of symptomatic urinary tract 
infection and rate of urinary tract infection in the first 30 days following pelvic 
reconstructive surgery.  
Secondary Outcome Measures 
1. Adverse Events  
a. Any adverse event related to drug administration will be reported. Adverse 
events not related to medication administration will not be collected. Please 
refer to section on Adverse Events for details of reportable criteria. 
2. Medication compliance 
a. All participants will need to complete a medication diary during the study 
drug treatment period. They will be asked to return this diary at their follow 
up. Medication compliance will be assessed and analyzed by way of these 
medication diaries. 
STATISTICAL CONSIDERATIONS 
Calculations of sample size were based on comparisons of UTI rates in the nitrofurantoin 
and placebo arms.  According to published results, the UTI rate in the placebo arm was 
32% and approximately a 14-15% reduction was observed in the treatment arm.4,12 
Using this information, we designed our study to mimic these findings, and assumed a 
UTI reduction rate of 18% in the nitrofurantoin arm could be observed in our clinical 
setting. Based on this assumption, total sample size of 164 patients was projected to 
achieve 80% power with a two-sided α error of 0.05. We increased the total sample size 
to 180 to allow for a 10% dropout rate. However, due to primary investigator timeline 
and lack of attrition, recruitment ceased once the sample size of 164 was reached. The 
power was calculated by using the PASS 15 (2017, NCSS, LLC. Kaysville, Utah, USA). All 
analyses were conducted using an intent-to-treat principle, which included all women 


randomized and not withdrawn from the study. A per-protocol analysis was also 
performed, and only included patients that completed the study. 
 
Categorical data were compared using X2 or Fisher’s Exact test where appropriate. 
Continuous variables were compared using Student’s t-test or Wilcoxon rank sum where 
appropriate, and are presented as mean±standard deviation or median (interquartile 
range). We estimated risks for UTI with odds ratio (OR) and corresponding 95% 
confidence intervals (95% CI) calculated using logistic regression. A P value <0.05 
defined statistical significance. All analyses were conducted using SAS Enterprise Guide 
version 7.1 (SAS Institute, Cary, NC). No interim analysis was performed. 
 
STUDY MONITORING AND DOCUMENTATION 
The Principal Investigator will monitor the study and assess the need for amendments as 
the study progresses. A protocol revision may be necessary for reasons including but not 
limited to rights, safety of participants, welfare of participants, and thus, and 
amendment will be required. Appropriate approvals (i.e., IRB) of the revised protocol 
must be obtained prior to implementation at each site.  
 
Site Documentation 
All study documents included in this protocol that will be presented to subjects will be 
submitted to the IRB for approval. The primary site will maintain a study binder for all 
sites that will include the following:  
 Enrollment log of patients that have consented to be in the study 
(electronic version) 
 Protocol deviation log (electronic version) 
 Adverse event log (electronic version) 
 Investigator protocol and amendments 
 IRB submissions, modifications, and renewals 
 Data safety monitoring committee reports 
 IRB approved consent form 
 Data collection forms 
 
 


Monitoring 
Monitoring will be conducted by the data safety monitoring board (DSMB) throughout 
the study to ensure that the study is conducted in accordance with the study protocol. 
By verifying compliance, monitoring helps to safeguard the subject safety, ensure data 
quality, and provide ongoing training and support to ensure compliance. 
Data verification will occur at 6-month intervals to verify data, assess continued 
compliance with protocol. 
An interim analysis will be completed at 6 months from the study commencement date. 
The purpose of the interim analysis is to discern whether the trial can be stopped for 
early benefit, as well as evaluate for safety and efficacy. Interim data analyses will be 
presented to the Data Safety and Monitoring Board for their review and 
recommendation. 
Study Drug Information 
 Drug: Nitrofurantoin 100 mg capsules, with matched placebo, will be provided by 
Central Compounding Center South 
 Storage: all study medications will be in a secure, locked, climate controlled location 
accessible only to authorized study personnel. All study medications will be 
maintained at controlled room temperature between 20-25°C with excursions 
permitted from 15-30°C. 
 The principal investigator and/or her designee(s) will be responsible for ensuring 
accountability of study medications is maintained throughout the study for all study 
medications that is received, dispensed, and disposed of per institutional standards 
of procedures. This log will be maintained on the electronic application, Vestigo. 
 Only participants enrolled and randomized in this study may receive study 
medications 
 All unused study medications will be destroyed per the institution’s destruction 
policy 
Protocol Deviations 
Protocol deviations will be documented and logged on the Protocol Deviations log 
(electronic version). This will be done for every protocol related deviation related to any 
portion of the study timeline. Deviations will be reviewed and evaluated on an ongoing 
basis, and, as necessary, appropriate corrective and preventive actions (including 
notification, re-training, or discontinuation) will be put in place. 
 
 


Data Safety Monitoring Board (DSMB) 
A data safety monitoring board (DSMB) will be comprised of an external physician and 
research nurse. They will be tasked to review all adverse events that occur across both 
study sites. A semi-annual report of all adverse events will be generated and sent to the 
Data Safety Monitoring Committee every 6 months. 
All Serious Adverse Events (SAEs) will be reported to the DSMB via email within 2 days 
of site staff being informed of its occurrence. The PI and research nurse will be cc’d on 
all communications with the DSMB. Copies of de-identified source documentation 
regarding the SAE will be included, as well as other clinically meaningful documentation. 
The PI will be responsible for ensuring that all sites comply with the DSMB requests. 
Reporting Adverse Events 
 
 
 
Adverse events (AE) will be recorded and reported per the criteria and timeline below.  
 
All AEs must be recorded and entered into the AE log and REDCap. An event number will 
be assigned by each site and recorded.  
 
SAEs must be reported to the DSMB within two business days as outlined above in the 
Data Safety Monitoring Committee section. 
 
Reportable AEs include those determined to be related to the study medication. AEs not 
related to the study medications will not be collected. Please note that underlying 
diseases are not reportable AEs unless there is an increase in severity or frequency 
during the course of the investigation. Death should not be recorded as an AE, but as an 
outcome of a specific SAE.  
 
Any participant that suffers an allergic reaction to the study medications will be 
unblinded. This will be a reported adverse event that will also be reported to the DSMB, 
as outlined above.  
 
Adverse Event Definitions 
 
Adverse Event: any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including abnormal laboratory finding) in subjects, whether or 
not related to study medications 
 
Serious Adverse Event: an adverse event that led to: 
 Death 
 Serious deterioration in the health of the subject that either resulted in 
o A life-threatening illness or injury 


o A permanent impairment of a body structure or a body function 
o Medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or body 
function 
 
Unrelated: No evidence that the timing of the AE has a relationship to the time study 
medications were taken 
 
Possibly Related: The AE has a timely relationship to the study medications, however a 
potential alternative etiology may be responsible for the AE 
 
Probably Related: The AE has a timely relationship to the study medications and the 
causative relationship can clearly be established. No potential alternative etiology is 
apparent. 
 
Severity Definitions 
 
Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant 
type causing no loss of time from normal activities. Symptoms do not require therapy or 
a medical evaluation; signs and symptoms are transient.  
 
Moderate: Events introduce a low level of inconvenience or concern to the participant 
and may interfere with daily activities, but are usually improved by simple therapeutic 
measures; moderate experiences may cause some interference with functioning.  
 
Severe: Events interrupt the participant’s normal daily activities and generally require 
systemic drug therapy or other treatment; they are usually incapacitating. 
 
 
 
 
 
 
 
 


 
REFERENCES 
 
1. Van der Wall E, Verkooyen RP, Mintjes-de Groot J et al. Prophylactic ciprofloxacin for 
catheter-associated urinary-tract infection. Lancet 1992;339:946–51. 
2. Ghezzi F, Serati M, Cromi A et al. Prophylactic single-dose prulifloxacin for catheter-
associated urinary tract infection after tension-free vaginal tape procedure. Int 
Urogynecol J 2007; 18: 753-757. 
3. Dieter AA, Amundsen CL, Edenfield AL et al. Oral Antibiotics to Prevent Postoperative 
Urinary Tract Infection. Obstet Gynecol 2014; 123(1): 96-103. 
4. Jackson D, Higgins E, Bracken J et al. Antibiotic Prophylaxis for Urinary Tract Infection 
After Midurethral Sling: A Randomized Controlled Trial. Female Pelvic Med Reconstr 
Surg 2013; 19(3): 137-41. 
5. Sutkin G, Alperin M, Meyn L et al. Symptomatic urinary tract infections after surgery for 
prolapse and/or incontinence. Int Urogynecol J 2010; 21: 955.  
6. Dieter AA, Amundsen CL, Visco AG, Siddiqui NY. Treatment for urinary tract infection 
after midurethral sling: a retrospective study comparing patients who receive short- 
term postoperative catheterization and patients who pass a void trial on the day of 
surgery. Female Pelvic Med Reconstr Surg 2012;18(3):175–8.  
7. Vigil H, Mallick R, Nitti V et al. Risk Factors for Urinary Tract Infection following Mid 
Urethral Sling Surgery. J Urol 2017;197(5): 1268-73.  
8. Schiotz HA, Guttu K. Value of urinary prophylaxis with methenamine in gynecologic 
surgery. Acta Obstet Gynecol Scand 2002; 81: 743-46. 
9. Albo ME, Richter HE, Brubaker L et al. Burch colposuspension versus fascial sling to 
reduce urinary incontinence. N Engl J Med 2007; 356:2143-2155. 
10. Sutkin G, Lowder JL, Smith KJ. Prophylactic antibiotics to prevent urinary tract infection 
during clean intermittent self-catheterization (CISC) for management of voiding 
dysfunction after prolapse and incontinence surgery: a decision analysis. Int Urogynecol 
J 2009; 20:933-38. 
11. Falagas, ME, Athanasiou S, Iavazzo C et al. Urinary tract infections after pelvic floor 
gynecological surgery: prevalence and effect of antimicrobial prophylaxis. A systematic 
review. Int Urogynecol J 2008; 19: 1165-1172. 
12. Rogers RG, Kammerer-Doak D, Olsen A et al. 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;191:182–7. 
13. Wolf SJ, Bennett CJ, Dmochowski RR et al. (2012). Urologic Surgery Antimicrobial 
Prophylaxis. American Urological Association. Retrieved from 
http://www.auanet.org/guidelines/antimicrobial-prophylaxis-(2008-reviewed-and-
validity-confirmed-2011-amended-2012) 
14. Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, Forward KR, Low DE et al. How long 
should catheter-acquired urinary tract infection in women be treated? A randomized 
controlled study. Ann Intern Med 1991; 114:713. 


15. Niël-Weise BS and van den Broek PJ. Antimicrobial policies for short-term catheter 
bladder drainage in adults. Cochrane Database Syst Rev 2005; (3):CD005428. 
16. Antibiotic Susceptibility Surveillance Report. Carolinas Health Care System. 2014. 
17. Tunitsky-Bitton E, Murphy A, Barber MD, et al. Assessment of voiding after sling: a 
randomized trial of 2 methods of postoperative catheter management after midurethral 
sling surgery for stress urinary incontinence in women. Am J Obstet Gynecol 
2015;212:597.e1-9. 
18. Hooten TM, Bradley SF, Cardenas DD et al. Diagnosis, Prevention, and Treatment of 
Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical 
Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010; 
50(5): 625-63. 
19. Rodríguez-Martínez JM, Ballesta S, Pascual A. Activity and penetration of fosfomycin, 
ciprofloxacin, amoxicillin/clavulanic acid and co-trimoxazole in Escherichia coli and 
Pseudomonas aeruginosa biofilms. Int J Antimicrob Agents 2007 Oct;30(4):366-8.  
20. Sastry S, Doi Y. Fosfomycin: Resurgence of an old companion. J Infect Chemother 2016 
May;22(5):273-80. doi: 10.1016/j.jiac.2016.01.010.  
21. Jancel T, Dudas V. Management of uncomplicated urinary tract infections. West J Med 
2002; 176(1): 51-55. 
22. Goettsch WG, Janknegt R, Herings RMC. Increased treatment failure after 3-days' 
courses of nitrofurantoin and trimethoprim for urinary tract infections in women: a 
population-based retrospective cohort study using the PHARMO database. Br. J. Clin. 
Pharmacol. 58:184–189. 
 
 
 
 


 
Figure 1. Study Trial Flow 
 
 
 
 
 
Group 1  
(Nitrofurantoin during 
catheterization) 
Group 2 
(Nitrofurantoin after 
catheterization) 
Released from office with bottle of medication 
Maintain medication diary 
First dose taken in office 
 
Patients Identified and Consented Postoperatively after failure of 
voiding trial 
Randomization after Passing Voiding Trial in Office (1-7 days 
following surgery) 
Group A 
(Nitrofurantoin AFTER 
catheterization) 
Group B 
(Placebo AFTER 
catheterization) 
Participants Screened and Consented at Preoperative Appointment 
 
Monitor for UTI x 30 days 
1st postoperative follow-up 1 -2 weeks later 
Return unused study medication 
Return medication diary 

ICF_001.pdf: 
Official Title:  Nitrofurantoin Administration for the Prevention of Short-Term Catheter Associated 
Urinary Tract Infection After Pelvic Surgery (NAUTICA): A Randomized Controlled Trial  
IRB-Approved Date: 7/11/2018
NCT03287089


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 1 of 10 
 
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
CAROLINAS HEALTHCARE SYSTEM 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
 
Sponsor / Study Title: 
  
Carolinas HealthCare System-Department of OB/GYN / 
Nitrofurantoin Administration for the Prevention of Short-
Term Catheter Associated Urinary Tract Infection After 
Pelvic Surgery (NAUTICA): A Randomized Controlled Trial 
 
Protocol Number: 
 
08-17-03  
Principal Investigator: 
(Study Doctor) 
 
Dina A. Bastawros, M.D. 
 
Telephone: 
 
 
 (24 Hours) 
 (24 Hours) 
 
Address: 
Carolinas HealthCare System 
 
 
 
 
Carolinas HealthCare System 
 
 
 
 
You will be given a signed and dated copy of the full Informed Consent Form. 
 
WHAT ARE SOME GENERAL THINGS YOU SHOULD KNOW ABOUT 
RESEARCH STUDIES? 
 
You are being asked to take part in a research study.  To join the study is voluntary. 
You may refuse to join, or you may withdraw your consent to be in the study, for any reason, 
without penalty or loss of benefits to you. 
 
Research studies are designed to obtain new knowledge. This new information may help people 
in the future.   You may not receive any direct benefit from being in the research study. There 
also may be risks to being in research studies. Deciding not to be in the study or leaving the 
study before it is done will not affect your relationship with the researcher, your health care 
provider, or the Carolinas Health Care System and its affiliates.  
 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 2 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
If you are a patient with an illness, you do not have to be in the research study in order to 
receive health care. 
 
Details about this study are discussed below.  It is important that you understand this 
information so that you can make an informed choice about being in this research study.  
 
You will be given a signed and dated copy of this consent form.  You should ask the researchers 
named above, or staff members who may assist them, any questions you have about this study at 
any time. 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
Urinary tract infections (UTI) are the most common complication after pelvic organ prolapse or 
urinary incontinence surgery. It can affect up to 35% of women undergoing these surgeries. 
 
Sometimes, the risk of a UTI is increased with the use of a catheter. A catheter is placed after 
surgery if you have difficulty emptying your bladder. Difficulty emptying your bladder can 
happen in up to 50% of women undergoing pelvic organ prolapse or incontinence surgery. 
Because of this, all of our patients have bladder testing after surgery to make sure they are able 
to void (urinate) after surgery. If they are not able to void, they must go home with a catheter. 
 
Complications of UTIs can include kidney infection and bloodstream infection. Therefore, it is 
important to reduce the risk of a UTI after surgery. However, using antibiotics too often can 
cause development of resistant organisms, making it difficult to treat bacterial infections. 
 
There has been research done to evaluate many different types of antibiotics to prevent UTIs in 
women that need to have a catheter for a few days following surgery. There is also some 
research that shows that no antibiotics may be needed in these women. Although some of these 
studies show that antibiotics can help reduce the number of UTIs, the type of antibiotic and 
treatment duration is not well defined.  
 
The purpose of this research study is to learn if an antibiotic is effective in reducing the risk of 
UTI after the short-term catheter is removed following surgery. 
 
You are being asked to be in the study because you plan to undergo surgery for pelvic organ 
prolapse and/or urinary incontinence. 
 
HOW LONG WILL YOUR PART IN THE STUDY LAST? 
 
Your participation in this study will include the office visit in which you are enrolled, your 
operation, and your postoperative recovery time. As part of your routine care, you will have a 
bladder test done in the hospital after your surgery.  
 
If you are unable to successfully void, you will be discharged home with a catheter. You will 
return to the office in 1-7 days for catheter removal. At that time, if you have consented to 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 3 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
participate in the study, you will be given 5 day supply of either an antibiotic or placebo 
medication (“study drug”) that you are to take two times a day until finished. You will need to 
keep a medication log of all the times you have taken the study drug. 
 
You will follow up at your previously scheduled 2 and 6-week follow-up appointments. Your 
involvement in the study will then be complete.  
 
ARE THERE ANY REASONS YOU SHOULD NOT BE IN THIS STUDY? 
 
You should not be in this study if you have had a UTI before surgery, have kidney problems, are 
pregnant, or have an allergy to the antibiotic (nitrofurantoin). 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
 
There will be approximately 180 people in this research study. 
 
VOLUNTARY PARTICIPATION 
 
Your participation in this research is entirely voluntary. It is your choice whether to participate 
or not. Whether you choose to participate or not, all the services you receive at this clinic will 
continue and nothing will change. If you choose not to participate in this research project, you 
will be offered the treatment that is routinely offered in our practice for UTI. You may change 
your mind later and stop participating even if you agreed earlier. 
 
The study doctors will receive no financial benefit in any form by asking you to participate in 
this study. 
WHAT WILL HAPPEN IF YOU TAKE PART IN THE STUDY? 
• 
Before surgery you will be screened to ensure you do not have a UTI. 
• 
Following surgery, you  may have a catheter in place. When it is time, if you have a 
catheter in place, you will have a bladder study. The study nurses will fill your bladder 
with fluid, remove the catheter, and give you 60 minutes to urinate. The study nurses will 
then measure how much urine you voided, and how much urine is left behind in your 
bladder. 
o If you urinated more than 200mL (less than 1 cup) and have less than 1/3 of the 
total urine volume left in your bladder, you have successfully voided and your 
involvement in the study is complete. 
o You will be asked to complete a questionnaire assessing how forceful you feel 
your stream of urine was. 
o If you are unable to urinate more than 200mL, and you have more than 1/3 of 
the total urine volume left in your bladder, then you have not successfully 
voided. A Foley catheter will be replaced and you will go home with this catheter. 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 4 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
• 
You will return to the office in 1-7 days for a repeat bladder study, similar to what was 
done in the hospital. If you successfully urinate, you will be randomized, or assigned by 
chance, like flipping a coin, to a study group.  
o All women in study Group A will be given a 5-day supply of nitrofurantoin, 
which is an antibiotic approved by the U.S. Food and Drug Administration 
(FDA) to treat UTI. This will be taken two times a day until all pills are gone.  
o All women in study Group B will be given a 5-day supply of a placebo. This will 
be taken two times a day until all pills are gone.  
o Both the antibiotic (nitrofurantoin) and placebo pills will look exactly the same. 
A placebo looks like real medicine but it does not have any active ingredients. 
Sometimes when we want to know whether a new medicine is good, we give 
some people the new medicine and some people the placebo. For the research to 
be good, it is important that you do not know whether you have been given the 
real medicine or the placebo.  This is one of the best ways we have for knowing 
what the medicine we are testing does. 
o It is important that neither you nor we know which of the two drugs you are 
given. This information will be in our files, but we will not look at these files 
until after the research is finished. This is the best way we have for testing 
without being influenced by what we think or hope might happen. We will then 
compare which of the two has the best results. 
• 
The first pill will be taken in the office. You will complete a medication log outlining 
every time you took a pill. You will need to bring this medication log with you at your 2-
week postoperative appointment.  
• 
You will return for a 6-week postoperative appointment. At that time, we will follow up 
with you to identify if you had any incidences of a UTI in the first 30 days following 
surgery. If you develop a UTI during the study, you will be treated with an antibiotic. 
• 
The study doctor and the team of Urogynecology physicians will be responsible for your 
health care throughout all study procedures. They will be looking after you and the other 
subjects very carefully during the study.  If we are concerned about what the study drug 
is doing, we will find out which study drug you are getting and make changes. If there is 
anything you are concerned about or that is bothering you about the research please talk 
to the researchers. 
INFORMATION ON NITROFURANTOIN 
 
The antibiotic that we are testing is called nitrofurantoin. It is an antibiotic that is commonly 
prescribed to treat UTIs, as well as prevent them. We now want to test this antibiotic to see if it 
can prevent UTIs in women who had a catheter after surgery.  
 
Side effects of nitrofurantoin include:  
• diarrhea 
• nausea 
• vomiting 
• vaginal discharge 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 5 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
• upset stomach  
• gas 
 
Some subjects in the research will not be given the antibiotic, which we are testing. Instead, they 
will be given a placebo, which does not have any active ingredients in it. There is no risk 
associated with taking placebo, although it is possible that your risk of getting a UTI may be 
higher (that is what this study is trying to find out).  
 
WHAT ARE THE POSSIBLE BENEFITS FROM BEING IN THIS STUDY? 
 
Research is designed to benefit society by gaining new knowledge.  You will not benefit 
personally from being in this research study.  
  
WHAT ARE THE POSSIBLE RISKS OR DISCOMFORTS INVOLVED FROM 
BEING IN THIS STUDY? 
 
There may be uncommon or previously unknown risks. You should report any problems to the 
researcher. The risks associated with this study are minimal. Potential risks you may experience 
may be a small risk of developing a UTI from catheterization.  However, this is the standard 
treatment for women who are unable to void after surgery.  You should let your study doctor 
know if you have signs or symptoms of a UTI (for example, burning or pain on urination or 
bloody or cloudy urine).  
 
Another risk may be drug intolerance (for example, if you take nitrofurantoin, your body could 
become resistant to its ability to kill UTI-causing bacteria).  
 
If you are a woman who is pregnant or is planning to get pregnant, you should not be in the 
study, as nitrofurantoin could cause harm to a developing fetus. 
 
IF YOU CHOOSE NOT TO BE IN THE STUDY, WHAT OTHER TREATMENT 
OPTIONS DO YOU HAVE? 
 
Whether or not you are in this study, you will receive standard surgical care for your condition. 
This may or may not include antibiotics to prevent UTI – this depends on your surgeon’s 
standard practices. You would get treated for a UTI if you develop one whether or not you are 
in this study. The study doctor will discuss the risks and benefits of other treatments with you. 
 
WHAT IF WE LEARN ABOUT NEW FINDINGS OR INFORMATION DURING 
THE STUDY?  
 
You will be given any new information gained during the course of the study that might affect 
your willingness to continue your participation.  
 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 6 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
CONFIDENTIALITY 
 
The records of this study will be kept private.  In any sort of report we might publish, we will 
not include any information that will make it possible to identify a patient.  Your record for this 
study may, however, be reviewed and/or photocopied by Carolinas HealthCare System, or by 
representatives of the Food and Drug Administration or other government agencies.  To that 
extent, confidentiality is not absolute. 
 
To ensure that your information collected for this study will be kept private, your name will not 
be used whenever possible.  A code will be used instead of your name.  All of your study data 
will be kept in a secure location. 
 
HOW WILL YOUR PRIVACY BE PROTECTED? 
 
No subject will be identified in any report or publication about this study.  Although every effort 
will be made to keep research records private, there may be times when federal or state law 
requires the disclosure of such records, including personal information.  This is very unlikely, but 
if disclosure is ever required, Carolinas Health Care System will take steps allowable by law to 
protect the privacy of personal information.  In some cases, your information in this research 
study could be reviewed by representatives of the medical center, research sponsors, or 
government agencies (for example, the FDA) for purposes such as quality control or safety. 
• 
If you choose to enroll in this study by signing this consent form, you will be assigned a 
study number that will be used on all examination forms and questionnaires; no other 
identifying information will be used on these forms. 
• 
Your signed consent forms will be maintained in two places: one copy will be kept in 
your medical record and a second copy will be kept in a locked file cabinet in a locked 
office. The copy in your medical record will allow the study doctors caring for you to 
know what study procedures you may be receiving as a part of the study and know how 
to take care of you if you have other health problems or needs during the study. 
• 
Only the study personnel: the study doctor, Faculty Advisors, and the Study Coordinator 
and affiliated study personnel will have access to an electronic file linking your name to 
your study number.  This file will be maintained on a password protected computer 
system and terminal and will be destroyed when the entire study is complete. 
WILL YOU RECEIVE ANYTHING FOR BEING IN THIS STUDY? 
 
You will not receive anything for taking party in this study. 
 
WILL IT COST YOU ANYTHING TO BE IN THIS STUDY? 
 
It will not cost you anything in addition to what you will be billed for your routine medical care 
to be in this study.  All tests, visits or procedures other than what is done for this study will be 
related to medical care that is part of the usual care for your condition and would be suggested 
even if you decided not to be in the research study. 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 7 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
 
Here are some examples of standard medical care that may be performed within this 
study:  office urinalysis, urine culture, and a voiding trial. 
 
WHAT WILL HAPPEN IF YOU ARE INJURED BY THIS RESEARCH? 
 
If you become ill or are hurt while you are in the study, get the medical care that you need right 
away. 
 
All research involves a chance that something bad might happen to you.  This may include the 
risk of personal injury. Despite all safety measures, you might develop a reaction or injury from 
being in this study. If such problems occur, the researchers will help you get medical care, but 
any costs for the medical care will be billed to you and/or your insurance company. The 
Carolinas Health Care System has not set aside funds to pay you for any such reactions or 
injuries, or for the related medical care. You do not give up any of your legal rights by signing 
this form. 
 
WHAT IF YOU WANT TO STOP BEFORE YOUR PART IN THE STUDY IS 
COMPLETE? 
 
Your participation in this study is completely voluntary. You should feel under no pressure to be 
in the study.  If you decide not to be in the study, that will not in any way harm your relations 
with your doctors or with Carolinas HealthCare System.  You are free to stop being in the study 
if you change your mind after entering it.  This would not harm your relations with your doctors 
or Carolinas HealthCare System. 
 
You can withdraw from this study at any time, without penalty.  The study doctors also have the 
right to stop your participation at any time. This could be because you have had an unexpected 
reaction, or have failed to follow instructions, or because the entire study has been stopped. 
You will still have all the benefits that you would otherwise have at this clinic. You may stop 
participating in the research at any time that you wish without losing any of your rights as a 
patient here. Your treatment at this clinic will not be affected in any way. 
 
AUTHORIZATION TO DISCLOSE HEALTH INFORMATION 
 
If you wish to take part in this clinical study, you will be asked to sign this consent form.  It 
allows the study sponsor and the study investigator to collect, process and pass on to the 
sponsor organizations any relevant personal health information collected from you during the 
study.  These are activities routinely carried out during all clinical studies. 
 
You have been told that personal information about you (including sensitive personal health 
information, such as your medical history and your racial/ethnic origin if relevant to the study) 
will be reviewed, collected on a computer database, stored in electronic or manual files, audited, 
and/or otherwise processed by: 
 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 8 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
• the study doctor and study staff, 
• the study sponsor and/or its associated companies, Carolinas HealthCare System, 
• regulatory or other governmental authorities of the United States and other countries, 
• other persons authorized by the study sponsor, 
• Carolinas HealthCare System employees, 
• other persons or agencies as required by law or allowed by federal regulations. 
 
You have been told that your personal data are being collected and processed to: 
 
• check your suitability to take part in the study, 
• monitor your treatment with the study drug, 
• compare and pool study treatment results with those of other subjects in clinical studies, 
• support the development of the study drug, 
• support the licensing application for regulatory approval of the study drug in the world  
• support the marketing, distribution, sale and use of the study drug anywhere in the 
world.    
 
You have been told that your personal information may be processed within the U.S. or 
elsewhere in the world or transferred to or from the U.S. for review, processing and/or storage 
by an associated company or a carefully selected third-party organization.  By signing this 
document, you explicitly consent to the transfer of your personal information, including 
sensitive personal information, collected during this clinical study, for review, processing and/or 
storage.  Your personal health information may be further shared by the groups above.  If 
shared by them, the information will no longer be covered by the Privacy Rule.  However, the 
groups are committed to keeping your personal health confidential. 
 
You may refuse this authorization to transfer your personal information.  If you choose not to 
agree to this authorization, you might be ineligible to participate in the study.  If you decide not 
to sign this authorization, that will not harm your relations with your doctors or with Carolinas 
HealthCare System.   
 
You have the right to inspect your medical record at any time. Your research record may be 
unavailable until the conclusion of the study. At that point, it will be available.  Please speak with 
the study doctor if you desire to access your record. 
 
You have been told whenever your personal information is processed; it will be kept confidential 
and secure, to the best of our ability.  It will be used only for the purpose for which it was 
collected. 
 
This Authorization does not have an expiration date. You have been told that according to the 
guidelines for good clinical practice, the study investigator and sponsor will keep your personal 
information for at least 6 years. If you do not withdraw this Authorization in writing, it will 
remain in effect indefinitely.   


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 9 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
 
If you wish to revoke authorization to use your personal information, you will notify the study 
doctor in writing at the address and telephone number listed on the first page of this form. Some 
of the data obtained from your record prior to your revocation may still be used if considered 
necessary for the study.   
 
WHOM TO CONACT ABOUT THIS STUDY 
 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the Investigator at the 
telephone number listed on the first page of this consent document.  If you seek emergency care, 
or hospitalization is required, alert the treating physician that you are participating in this 
research study.   
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research subjects.  If you have any questions about your rights as a research subject, 
and/or concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
 
 
 
• or call toll free:        
 
• or by email:             
 
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00022622. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 


Carolinas HealthCare System-Department of OB/GYN / Protocol Number 08-17-03 
Page 10 of 10 
 
  
 
Dina A. Bastawros, M.D. 
Advarra IRB Approved Version 11 Jul 2018 
 
 
 
 
 
 
 
STATEMENT OF CONSENT  
 
I have read this form and its contents were explained to me.  I agree to be in this research study 
for the purposes listed above.  All of my questions were answered to my satisfaction.  I will 
receive a signed and dated copy of this form for my records.  I am not giving up any of my legal 
rights by signing this form.   
 
___________________________ 
____/____/____  _________ 
Signature of Research Subject 
 
Date 
Time 
 
___________________________________ 
Printed Name of Research Subject 
 
STATEMENT OF PERSON EXPLAINING CONSENT  
 
I have carefully explained to the subject the nature and purpose of the above study.  There has 
been an opportunity for the subject to ask questions about this research study.  I have been 
available to answer any questions that the subject has about this study. 
 
___________________________ 
____/____/____  _________ 
Signature of Person Explaining Consent 
Date 
 
Time 
 
___________________________________ 
Printed Name of Person Explaining Consent