EPOV: Effect of Phenazopyridine on Prolapse Surgery Voiding Trials

• Sponsor: University of Massachusetts, Worcester (Other)
• Overall Status: Completed
• CT.gov ID: NCT03065075
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 2
• Actual Duration (Months): 24.9
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

To determine if phenazopyridine reduces the rate of postoperative urinary retention after pelvic organ prolapse surgery.

Condition or Disease	Intervention/Treatment	Phase
Urinary Retention Postoperative	Drug: Phenazopyridine	Phase 3

Detailed Description

Several tools can be used to evaluate for ureteral patency during urogynecologic procedures. Typically, surgeons use urine dyes such as methylene blue, indigotindisulfonate sodium, or phenazopyridine, with the latter being restricted to oral administration. However in June 2014, the two U.S. manufacturers of indigotindisulfonate sodium stopped producing the medication and there is no prospect that it will be returning soon. Phenazopyridine is an over-the-counter medication (Azo-Gesic, Baridium, Urinary Pain Relief) that has been used safely for decades as a bladder analgesic and taints the urine orange.

Over the past few months, increasing evidence suggests that phenazopyridine may reduce transient postoperative urinary retention. Transient urinary retention is common after urogynecologic surgery and is assessed postoperatively by performing a void trial (VT) prior to discharge. In a study designed to determine the time from administration of oral phenazopyridine to visualize dye from the ureters, Propst et al incidentally found that 38% of patients (19 of 49) failed postoperative VTs without phenazopyridine, but only 19% (9 of 47) failed with phenazopyridine, p=0.04. Most recently, a study by Duenas-Garcia et al designed to examine local anesthetics and urinary retention in subjects undergoing midurethral slings found that phenazopyridine decreased the VT failure rate from 30% to 8% (5). The investigators hypothesize that giving a dose of phenazopyridine the morning after surgery will significantly reduce the rate of postoperative urinary retention in women undergoing prolapse repair.

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Phenazopyridine on Prolapse Surgery Voiding Trials
• Actual Study Start Date: Feb 1, 2017
• Actual Primary Completion Date: Aug 28, 2018
• Actual Study Completion Date: Feb 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phenazopyridine Participant is given Phenazopyridine 200mg on postoperative day 1	Drug: Phenazopyridine; Phenazopyridine 200 mg on morning of postoperative day 1; Other Names: Pyridium
No Intervention: No Phenazopyridine Participant is not given Phenazopyridine on postoperative day 1

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Postoperative Urinary Retention After Pelvic Organ Prolapse Surgery (INTENT-TO-TREAT) [postoperative day 1]

   Rate of postoperative urinary retention after pelvic organ prolapse surgery as determined by those who failed a standardized void trial. A successful void trial is defined as a postvoid residual of less than half of the voided volume.

Other Outcome Measures

1. Number of Participants With Postoperative Urinary Retention After Pelvic Organ Prolapse Surgery (AS-TREATED) [postoperative day 1]

   Rate of postoperative urinary retention after pelvic organ prolapse surgery as determined by those who failed a standardized void trial. A successful void trial is defined as a postvoid residual of less than half of the voided volume.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women undergoing overnight admission after prolapse surgery

Exclusion Criteria:

• Unable to provide consent

• Under 18 years of age

• Pregnant women

• Prisoners

• Using intermittent self-catheterization preoperatively

• Neurological disease or spinal cord injury resulting in voiding dysfunction

• Undergoing spinal or epidural anesthesia for the procedure

• Allergy to phenazopyridine

• Renal insufficiency

• Liver disease

• Intra-operative bladder injury necessitating use of prolonged indwelling Foley catheter

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Massachusetts	Worcester	Massachusetts	United States	01605

Sponsors and Collaborators

• University of Massachusetts, Worcester

Investigators

• Principal Investigator: Michael Flynn, MD, UMass Worcester

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2017

More Information

Publications

None provided.

• Responsible Party: Michael Flynn, MD, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT03065075
• Other Study ID Numbers: H00012082
• First Posted: Feb 27, 2017
• Last Update Posted: Apr 16, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Urinary Retention; Prolapse

Study Results

Participant Flow

Arm/Group Title	Phenazopyridine on POD1	No Intervention on POD1
Arm/Group Description	Participant is given Phenazopyridine 200 mg on postoperative day 1 76 subjects were randomized into this arm 4 were removed from the intent-to-treat analysis: 1 had a bowel injury re-operation that precluded performing a void trial 1 intraoperative cystotomy that precluded performing a void trial 2 were using Foley catheters preoperatively, which was part of the exclusion criteria 72 subjects in the intent-to-treat analysis 3 did not receive the intervention: 1 was too nauseous 1 was erroneously missed 1 refused 69 subjects in the as-treated analysis	Subject is not given Phenazopyridine on postoperative day 1 76 subjects were randomized into this arm 2 were removed from the intent-to-treat analysis: 1 intraoperative cystotomy that precluded performing a void trial 1 had spinal anesthesia, which was part of the exclusion criteria 74 subjects in the intent-to-treat analysis 3 cross-overs were brought in from the intervention arm because they did not receive the medication 77 subjects in the as-treated analysis
Period Title: Overall Study
STARTED	76	76
Intent-to-treat Analysis	72	74
As-treated Analysis	69	77
COMPLETED	76	76
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phenazopyridine	No Phenazopyridine	Total
Arm/Group Description	Participant is given Phenazopyridine on morning of postoperative day 1	Participant is not given Phenazopyridine on morning of postoperative day 1	Total of all reporting groups
Overall Participants	76	76	152
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (12.8)	60.9 (13.5)	61.2 (13.2)
Sex: Female, Male (Count of Participants)
Female	76 100%	76 100%	152 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	61 80.3%	59 77.6%	120 78.9%
Non-white	14 18.4%	17 22.4%	31 20.4%
Declined to answer	1 1.3%	0 0%	1 0.7%
Concomitant hysterectomy (Count of Participants)
Count of Participants [Participants]	59 77.6%	62 81.6%	121 79.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Postoperative Urinary Retention After Pelvic Organ Prolapse Surgery (INTENT-TO-TREAT)
Description	Rate of postoperative urinary retention after pelvic organ prolapse surgery as determined by those who failed a standardized void trial. A successful void trial is defined as a postvoid residual of less than half of the voided volume.
Time Frame	postoperative day 1

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis

Arm/Group Title	Phenazopyridine	No Phenazopyridine
Arm/Group Description	Participant is given Phenazopyridine on morning of postoperative day 1	Participant is not given Phenazopyridine on morning of postoperative day 1
Measure Participants	72	74
Count of Participants [Participants]	30 39.5%	25 32.9%

2. Other Pre-specified Outcome

Title	Number of Participants With Postoperative Urinary Retention After Pelvic Organ Prolapse Surgery (AS-TREATED)
Description	Rate of postoperative urinary retention after pelvic organ prolapse surgery as determined by those who failed a standardized void trial. A successful void trial is defined as a postvoid residual of less than half of the voided volume.
Time Frame	postoperative day 1

Outcome Measure Data

Analysis Population Description

As-treated analysis

Arm/Group Title	Phenazopyridine	No Phenazopyridine
Arm/Group Description	Participant is given Phenazopyridine on morning of postoperative day 1	Participant is not given Phenazopyridine on morning of postoperative day 1
Measure Participants	69	77
Count of Participants [Participants]	28 36.8%	27 35.5%

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Phenazopyridine		No Phenazopyridine
Arm/Group Description	Participant is given Phenazopyridine Phenazopyridine: Phenazopyridine on morning of postoperative day 1 76 subjects were randomized into this arm 4 were removed from the intent-to-treat analysis: 1 had a bowel injury re-operation that precluded performing a void trial 1 intraoperative cystotomy that precluded performing a void trial 2 were using Foley catheters preoperatively, which was part of the exclusion criteria 72 subjects in the intent-to-treat analysis 3 did not receive the intervention: 1 was too nauseous 1 was erroneously missed 1 refused 69 subjects in the as-treated analysis		Participant is not given Phenazopyridine 76 subjects were randomized into this arm 2 were removed from the intent-to-treat analysis: 1 intraoperative cystotomy that precluded performing a void trial 1 had spinal anesthesia, which was part of the exclusion criteria 74 subjects in the intent-to-treat analysis 3 cross-overs were brought in from the intervention arm because they did not receive the medication 77 subjects in the as-treated analysis
All Cause Mortality
	Phenazopyridine		No Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)		0/76 (0%)
Serious Adverse Events
	Phenazopyridine		No Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)		0/76 (0%)
Gastrointestinal disorders
Bowel injury re-operation	1/76 (1.3%)	1	0/76 (0%)	0
Other (Not Including Serious) Adverse Events
	Phenazopyridine		No Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/76 (11.8%)		14/76 (18.4%)
Infections and infestations
Urinary tract infection	9/76 (11.8%)	9	14/76 (18.4%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

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