The Effect of Oral PhenazopyrIdine on Perioperative Voiding After Mid-urethral sliNg (EPIPhANy Study)

• Sponsor: University of Massachusetts, Worcester (Other)
• Overall Status: Completed
• CT.gov ID: NCT02806713
• Collaborator: (none)
• Enrollment: 92
• Location: 1
• Arms: 2
• Duration (Months): 18
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

Randomized clinical trial using phenazopyridine to decrease voiding dysfunction after a retropubic midurethral sling operation.

Condition or Disease	Intervention/Treatment	Phase
Dysfunctional Voiding; Postoperative Pain	Drug: Phenazopyridine; Other: no Phenazopyridine	Phase 3

Detailed Description

Study design and randomization This study is a randomized controlled trial. Randomization will be performed using software and a block randomization scheme. Study assignment will be completed using sequentially numbered sealed opaque envelopes. All the research procedures described other than the use or not of phenazopyridine will be applicable to both arms of the study. Subjects will have a 50% chances of getting either phenazopyridine or nothing.

Because pyridium turns the urine orange, it is impossible to blind the patients and researchers to the study assignment. Because there is no known placebo that turns the urine orange, there is no value to using an actual placebo tablet. Subjects will be assigned to either receive pyridium or not receive pyridium preoperatively.

Screening potential subjects: Investigators will screen potential subjects for contraindications to methylene blue. Prior obtaining the routine surgical consent for the potential subject's surgical procedure, the patient's medical history in the UMass Electronic Medical Record is routinely reviewed. The medical record will be reviewed for a diagnosis of G6PD and if found, the potential subject will be excluded.

Once written consent has been obtained, subject number will be assigned and the appropriate randomization envelope will be opened. The study assignment will not be formally shared with the subject. Those assigned to the "pyridium" arm will have orders written for the standard 200 mg dose of pyridium to be given on arrival to the Surgical Admissions Care Unit (SACU). Those assigned to the "NO pyridium" arm with have their routine preoperative orders written along with an order for "No preoperative pyridium".

Subjects will then follow the routine perioperative care for their procedures with the only study interventions being the gathering of PHI and performing postoperative pain assessments.

PHI will be obtained at the time of the surgical consent with the purpose to evaluate for possible confounders affecting the postoperative bladder function.

Surgical procedure:

The Mid Urethral Sling will be performed in standard fashion based on manufacturer's recommendations and instructions to minimize inter-observer variations. We will perform the procedure according to our usual and customary techniques. The subject will receive the same technique and interventions that a routine patient on the Urogyn service would expect to undergo. There will be no changes to the technique for the purpose of the study.

Bladder challenge:

Patient will undergo voiding trial at same day surgery per our usual and customary protocol. This is the same protocol the subject would undergo as a patient on the Urogyn service. The bladder challenge will be interpreted in our usual manner and the subject managed according to our routine clinical protocols.

Postoperative care:

Subjects will undergo routine postoperative care and followup. Subjects failing their bladder challenge will be seen in the Urogyn clinic according to routine clinical protocols and data concerning their void trials collected. Subjects will undergo routine followup evaluation 6 weeks postoperatively in the order to assess any potential long-term voiding dysfunction. Information on any postoperative complications will be collected

Administration of Visual analog scale:

(1) Visual analog scale for assessment of pain will be administered at two- time intervals.

1. VAS #1) Preoperative VAS will be done by the principal investigator or any of the study assistants. The VAS form will be part of subject's packet.

2. VAS#2) VAS will be administered by one of the study investigators 2 to 3 hours after the surgical procedure in the SACU.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Oral phenazopyrIdine on Perioperative Voiding After Mid-urethral Sling
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: no phenazopyridine Patients not receiving phenazopyridine (standard of care)	Other: no Phenazopyridine; Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided
Experimental: phenazopyridine Patients receiving phenazopyridine	Drug: Phenazopyridine; Other Names: Pyridium

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Failed Voiding Trial [Postoperatively, up to 3 days after surgery]

   Number of participants with a failed postoperative voiding trial. A failed voiding trial is defined as not voiding all urine in 20 minutes or voiding less than 1/3 of total volume (voided volume + post void residual). Patients will undergo voiding trial at same day surgery per the following protocol. Participants who do not pass the voiding trial the same day of their surgical procedure return to the clinic in 3 days to repeat it, following the same protocol described above.

Secondary Outcome Measures

1. Change in Participant-reported Pain From Pre to Post Procedure Using the Visual Analog Scale (VAS) [Preoperatively and then 2 to 3 hours after surgery]

   To determine if the phenazopyridine has an analgesic effect after the retropubic midurethral slings, participants will be asked to self-report pain intensity preoperatively and then postoperatively (2 to 3 hours post procedure) using the Visual Analog Scale (VAS). The scale of the VAS is from 0 meaning "no pain" to 10 indicating the "worst pain." The resulting change is measured as the difference between the self-reported preoperative pain score and the postoperative pain score.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Any female subjects scheduled to undergo Mid-Urethral Sling (MUS) through the UMass urogynecology service for incontinence.

Exclusion Criteria:

1. Planned concurrent prolapse or other procedure besides cystoscopy

2. Using intermittent self catheterization preoperatively

3. Undergoing spinal anesthesia for the procedure

4. Known allergy to phenazopyridine (AKA Pyridium)

5. Renal insufficiency

6. Any condition or situation that in the attending physician's opinion would contra-indicate the use of phenazopyridine

7. Subjects not competent to give consent

8. Prisoners

9. Non-English speaking patients

10. Age <18

11. Pregnant patients

12. Contraindications to the use of IV methylene blue including

13. Patients with known hypersensitivity reactions

14. Severe renal insufficiency

15. Patients with G6PD deficiency

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Umass Memorial	Worcester	Massachusetts	United States	01605

Sponsors and Collaborators

• University of Massachusetts, Worcester

Investigators

• Principal Investigator: Michael K Flynn, MD, MHS, University of Massachusetts, Worcester

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 7, 2016

More Information

Publications

• Nilsson CG, Kuuva N, Falconer C, Rezapour M, Ulmsten U. Long-term results of the tension-free vaginal tape (TVT) procedure for surgical treatment of female stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2001;12 Suppl 2:S5-8.
• Nilsson CG, Palva K, Rezapour M, Falconer C. Eleven years prospective follow-up of the tension-free vaginal tape procedure for treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Aug;19(8):1043-7. doi: 10.1007/s00192-008-0666-z. Epub 2008 Jun 6.

• Responsible Party: Michael Flynn, Principal Investigator, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT02806713
• Other Study ID Numbers: H00008816
• First Posted: Jun 21, 2016
• Last Update Posted: Feb 5, 2019
• Last Verified: Jan 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.: Yes
• Additional relevant MeSH terms: Pain, Postoperative

Study Results

Participant Flow

Arm/Group Title	no Phenazopyridine	Phenazopyridine
Arm/Group Description	Patients not receiving phenazopyridine (standard of care) no Phenazopyridine: Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided	Patients receiving phenazopyridine Phenazopyridine
Period Title: Overall Study
STARTED	46	46
COMPLETED	44	44
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	no Phenazopyridine	Phenazopyridine	Total
Arm/Group Description	Patients not receiving phenazopyridine (standard of care) no Phenazopyridine: Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided	Patients receiving phenazopyridine Phenazopyridine	Total of all reporting groups
Overall Participants	44	44	88
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	44 100%	44 100%	88 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.7 (9.4)	49.7 (12.6)	48.7 (11.1)
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	47.7	49.7	48.7
Sex: Female, Male (Count of Participants)
Female	44 100%	44 100%	88 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 11.4%	8 18.2%	13 14.8%
Not Hispanic or Latino	39 88.6%	36 81.8%	75 85.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.3%	1 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 4.5%	5 11.4%	7 8%
White	33 75%	29 65.9%	62 70.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	9 20.5%	9 20.5%	18 20.5%
Region of Enrollment (participants) [Number]
United States	44 100%	44 100%	88 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Failed Voiding Trial
Description	Number of participants with a failed postoperative voiding trial. A failed voiding trial is defined as not voiding all urine in 20 minutes or voiding less than 1/3 of total volume (voided volume + post void residual). Patients will undergo voiding trial at same day surgery per the following protocol. Participants who do not pass the voiding trial the same day of their surgical procedure return to the clinic in 3 days to repeat it, following the same protocol described above.
Time Frame	Postoperatively, up to 3 days after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	no Phenazopyridine	Phenazopyridine
Arm/Group Description	Patients not receiving phenazopyridine (standard of care) no Phenazopyridine: Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided	Patients receiving phenazopyridine Phenazopyridine
Measure Participants	44	44
Passed the voiding trial	35 79.5%	32 72.7%
Failed a voiding trial	9 20.5%	12 27.3%

2. Secondary Outcome

Title	Change in Participant-reported Pain From Pre to Post Procedure Using the Visual Analog Scale (VAS)
Description	To determine if the phenazopyridine has an analgesic effect after the retropubic midurethral slings, participants will be asked to self-report pain intensity preoperatively and then postoperatively (2 to 3 hours post procedure) using the Visual Analog Scale (VAS). The scale of the VAS is from 0 meaning "no pain" to 10 indicating the "worst pain." The resulting change is measured as the difference between the self-reported preoperative pain score and the postoperative pain score.
Time Frame	Preoperatively and then 2 to 3 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	no Phenazopyridine	Phenazopyridine
Arm/Group Description	Patients not receiving phenazopyridine (standard of care) no Phenazopyridine: Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided	Patients receiving phenazopyridine Phenazopyridine
Measure Participants	44	44
Mean (Standard Deviation) [score on a scale]	1.76 (1.31)	1.21 (1.2)

Adverse Events

Time Frame	Up to six weeks postoperatively
Arm/Group Title	no Phenazopyridine		Phenazopyridine
Arm/Group Description	Patients not receiving phenazopyridine (standard of care) no Phenazopyridine: Because the obvious effects on the urine coloration of pyridium no placebo or dummy are provided		Patients receiving phenazopyridine Phenazopyridine
All Cause Mortality
	no Phenazopyridine		Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/44 (0%)
Serious Adverse Events
	no Phenazopyridine		Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	no Phenazopyridine		Phenazopyridine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/44 (0%)

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.