Pelvic Organ ProlapsePhase 4NCT02727322
Nitrofurantoin Prophylaxis During Catheter-managed Acute Urinary Retention After Pelvic Reconstructive Surgery
A Phase 4 study testing Nitrofurantoin in people with Pelvic Organ Prolapse, run by Halina M Zyczynski, MD at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pelvic Organ Prolapse
- What is being tested?
- Nitrofurantoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 154 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2016to 12 May 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women who have undergone surgery for the correction of pelvic organ prolapse and/or urinary incontinence and failed a postoperative voiding trial
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
Georgetown/MedStar Hospital Center
Washington D.C., District of Columbia, 20007
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Pelvic Organ Prolapse
- Being tested
- Nitrofurantoin, Placebo
- Medical subject headings
- Pelvic Organ Prolapse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitrofurantoinDrug
Also called Macrobid
Patients will receive nitrofurantoin 100mg once daily or a placebo. Pills will be identical.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Nitrofurantoin | Active comparator | Receives once daily nitrofurantoin 100mg Receives: Drug: Nitrofurantoin |
| Placebo | Placebo comparator | Receives matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Urinary Tract Infection Within 6 Weeks of Surgery
Frequency of symptomatic, culture-proven UTI; included participants who were empirically treated outside of protocol (symptoms but no culture) within 6 weeks of surgery.
Positive culture was defined as at least 100,000 colony forming units (cfu)/ml of uropathic bacteria in a catheterized or midstream clean catch voided urine specimen.
Measured: within 6 weeks of surgery
Secondary outcomes (2)
Number of Participants Who Experienced at Least One Adverse Event Symptom While Requiring Catheterization
This is the number of participants who experienced at least one adverse symptom as reported on the diary completed daily while requiring catheterization. These adverse symptoms included: constipation, nausea/vomiting, drowsiness, headache, flatulence, abdominal pain, dizziness, diarrhea, rash/itching, dyspepsia, fever/chills, amblyopia and other.
Measured: within 6 weeks of surgery
Frequency of Urine Cultures Positive for Nitrofurantoin-resistant Isolates
Frequency of urine cultures with one or more organisms resistant to nitrofurantoin. Positive culture was defined as at least 100,000 colony forming units (cfu)/ml of uropathic bacteria in a catheterized or midstream clean catch voided urine specimen.
Measured: within 6 weeks of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2016 (estimated)
- Study startAug 2016
- Primary completion27 Mar 2018
- Study completion12 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pelvic Organ ProlapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Halina M Zyczynski, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Halina M Zyczynski, MD, University of Pittsburgh
- Investigators
- Erin S Lavelle, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02727322
- Sponsor's protocol ID
- PRO15110557
- Status last verified
- May 2019
- First submitted
- 31 Mar 2016
- Last updated
- 29 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: No plan to make participant data available
Publications
Lavelle ES, Alam P, Meister M, Florian-Rodriguez M, Elmer-Lyon C, Kowalski J, Carter-Brooks C, Mazloomdoost D, Zyczynski H, Lowder J, Gutman R, Sutkin G. Antibiotic Prophylaxis During Catheter-Managed Postoperative Urinary Retention After Pelvic Reconstructive Surgery: A Randomized Controlled Trial. Obstet Gynecol. 2019 Oct;134(4):727-735. doi: 10.1097/AOG.0000000000003462.
PubMed 31503155
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Trial of Nitrofurantoin Prophylaxis During Catheterization for Acute Postoperative Urinary Retention After Pelvic Reconstructive Surgery
- ClinicalTrials.gov ID
- NCT02727322
- Acronym / sponsor ID
- PRO15110557
- Conditions
- Pelvic Organ Prolapse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- Halina M Zyczynski, MDUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- 27 Mar 2018 (actual)
- Study completion
- 12 May 2018 (actual)
- First posted
- 4 Apr 2016 (estimated)
- Results
- Posted 20 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrofurantoin | Active comparator | Drug: NitrofurantoinReceives once daily nitrofurantoin 100mg |
| Placebo | Placebo comparator | Drug: PlaceboReceives matching placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Women who have undergone surgery for the correction of pelvic organ prolapse and/or urinary incontinence and failed a postoperative voiding trial
Key exclusion criteria (7 listed)
- Known drug allergy to nitrofurantoin
- History of renal insufficiency
- Renal transplant
- Renal nephropathy
- Recent history of more than 3 UTIs per year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NitrofurantoinAlso: MacrobidPatients will receive nitrofurantoin 100mg once daily or a placebo. Pills will be identical. | Drug | Nitrofurantoin |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Number of Participants Experiencing Urinary Tract Infection Within 6 Weeks of Surgery
Time frame: within 6 weeks of surgery
Frequency of symptomatic, culture-proven UTI; included participants who were empirically treated outside of protocol (symptoms but no culture) within 6 weeks of surgery. Positive culture was defined as at least 100,000 colony forming units (cfu)/ml of uropathic bacteria in a catheterized or midstream clean catch voided urine specimen.
2 secondary outcomes
Number of Participants Who Experienced at Least One Adverse Event Symptom While Requiring Catheterization
Time frame: within 6 weeks of surgery
Frequency of Urine Cultures Positive for Nitrofurantoin-resistant Isolates
Time frame: within 6 weeks of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31503155Lavelle ES, Alam P, Meister M, Florian-Rodriguez M, Elmer-Lyon C, Kowalski J, Carter-Brooks C, Mazloomdoost D, Zyczynski H, Lowder J, Gutman R, Sutkin G. Antibiotic Prophylaxis During Catheter-Managed Postoperative Urinary Retention After Pelvic Reconstructive Surgery: A Randomized Controlled Trial. Obstet Gynecol. 2019 Oct;134(4):727-735. doi: 10.1097/AOG.0000000000003462.
- Individual participant dataSharing planned: No. No plan to make participant data available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erin S Lavelle, MD principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nitrofurantoin in people with Pelvic Organ Prolapse, run by Halina M Zyczynski, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Urinary Tract Infection Within 6 Weeks of Surgery (time frame: within 6 weeks of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02727322, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2019.