Bulking Agents for the Treatment of Stress Urinary Incontinence in Females

• Sponsor: Contura (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00629083
• Collaborator: Regulatory and Clinical Research Institute (RCRI) (Other)
• Enrollment: 345
• Locations: 34
• Arms: 2
• Actual Duration (Months): 61
• Patients Per Site: 10.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to demonstrate the safety and effectiveness of Bulkamid® in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD) in adult women who have SUI or stress predominant mixed incontinence

Condition or Disease	Intervention/Treatment	Phase
Stress Urinary Incontinence	Device: Bulkamid; Device: Contigen	N/A

Detailed Description

The study is a single-masked, randomized, comparative multi-center, 2-arm parallel study intended to demonstrate the safety and effectiveness of Bulkamid® vs. Contigen® for the treatment of stress urinary incontinence (SUI)due to intrinsic sphincter deficiency (ISD) in adult women who have SUI or stress predominant mixed incontinence.

Subjects will be randomized to receive either a polyacrylamide hydrogel (Bulkamid®) treatment, or a collagen treatment (Contigen®) using a 2:1 ratio and will be masked to the treatment. Screening baseline evaluations and collagen skin testing will be completed to determine eligible subjects. Following a negative skin test, a subject will be randomized and treated with Bulkamid® or the comparator device at the Treatment Visit.

Subjects that are not continent will be considered for re-injection. A maximum of 3 injections (initial + 2 re-injections) are allowed. After the last injection, subjects will attend the 3-Month, 6-Month and 12-Month Follow-up Visits plus a telephone contact at 9 months.

The study will record objective incontinence measurements, subject's perception of effectiveness and quality of life assessments. Adverse events will be recorded throughout the study.

Each subject will be followed for 12 months from the last injection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 345 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Single-Masked, Randomized, Multi-Center, 2-Arm Parallel Study Comparing the Safety and Effectiveness of Bulkamid® and Contigen® as Bulking Agents for the Treatment of Stress Urinary Incontinence in Females
• Actual Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Bulkamid Hydrogel injection	Device: Bulkamid; Bulking injection with Bulkamid injection device
Active Comparator: 2 Contigen injection	Device: Contigen; Transurethral bulking injection

Outcome Measures

Primary Outcome Measures

1. Primary Effectiveness Endpoint [12 Months]

   The number of subjects with at least a 50% reduction from baseline in both leakage, as measured by the 24h Pad Test, and daily number of incontinence episodes

2. The Number of Participants With Device- and Procedure-related Serious Adverse Events Through 12 Months Follow-up. [12 months]

   The number of participants with device- and procedure-related serious adverse events through 12 months follow-up.

Secondary Outcome Measures

1. 24hr Pad Test [12 months]

   A measure of urine leaked during a 24-hour period on a known weight and quantity of pads at the 12-month endpoint.

2. Number of Subjects Reporting as a Responder [12 months]

   At the 12-month primary endpoint follow-up visit, the subject was asked to provide her perception of treatment effectiveness by circling the most accurate description of her condition: cured/dry; much improved; improved; no change; worse. The response was dichotomized into responder or non-responder. A subject was classified as a responder if she reported that the treatment had cured, much improved, or improved her incontinence condition.

3. IQoL [12 months]

   The IQoL is a validated instrument consisting of 22 questions grouped into three subscales: avoidance and limiting behaviors; psychosocial impacts, and social embarrassment. It is a subject self-reported quality-of-life measure specific to urinary problems that is used to assess the impact of urinary incontinence and urinary problems and their treatment. The subject scores each question on a scale of 1 to 5 with higher scores indicating more positive responses. The maximum score was 110 points and the minimum score was 22.

4. ICIQ-UI Short Form [12 months]

   The ICIQ-UI Short Form assesses the impact of symptoms of incontinence on quality of life and outcome of treatment. The questionnaire consists of three questions with a maximum score of 21 and a minimum score of zero (0). A lower score represents a decrease in the severity of symptoms (i.e., improvement).

5. Number of Incontinence Episodes [12 months]

   The total number of incontinence episodes experienced by the subject over three consecutive days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be female 18 or more years of age.

• Females of childbearing potential or <2 years post-menopausal must be using 2 forms of contraception.

• Suffer from SUI for at least 6 months.

• Have failed 2 previous non-invasive therapies for 3 months each.

• Have at least 3 incontinence episodes measured over 3 days.

• Have a baseline 24h pad test weight greater than or equal to 5 gm.

• Have VLPP ≤ 100 cm H2O.

• Have maximum cystometric capacity equal or higher than (≥) 250 mL.

• Have PVR urine ≤ 100 mL.

• Have a life expectancy of more than 2 years.

Exclusion Criteria:

• Has urethral hypermobility >30 deg.

• Has predominant urge incontinence.

• Has detrusor overactivity.

• Regularly or intermittently users of urethral catheter.

• Has had previous radiation treatment in the pelvic floor.

• Has had previous urethral surgery (i.e. fistula, diverticula)or urethral bulking. Failed sling or colposuspension procedure for at least 6 months may be included.

• Suffers from known polyuria.

• Has had three (3) or more culture-proven bacterial UTIs in the last 12 months.

• Has a current infection (urethritis, cystitis or vaginitis).

• Has unevaluated hematuria.

• Has a Prolapse Stage greater than II.

• Has a BMI>35 kg/m2.

• Is taking pharmacological treatment for stress urinary incontinence, 4 weeks prior to screening.

• Is allergic to bovine collagen.

• Is known to suffer from severe allergies or anaphylaxis.

• Suffers from autoimmune diseases (e.e. connective tissue diseases) that could confound the treatment.

• Is currently taking or has taken systemic corticosteroids within the past 3 months.

• Currently has cancer or has a history of any cancer within the past 5 years (skin cancer with no evidence of skin malignancy, for at least 2 years, can be included).

• Currently suffering from unstable cardiovascular disease, cancer or uncontrolled diabetes.

• Has active herpes genitalis.

• Is currently participating in any other clinical trial or has participated in another clinical trial within 3 months of screening/baseline visit.

• Is pregnant, lactating or intending to become pregnant.

• Is not physically able to perform study procedure.

• Has a neurogenic bladder

• Had a vaginal delivery within 3 months prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Incontinence Research Institute	Encinitas	California	United States	92024
2	Tower Urology - Institute for Continence - Cedars-Sinai Medical Office	Los Angeles	California	United States	90048
3	Sherif Aboseif, MD	Oxnard	California	United States	93030
4	South California Permanente Medical Group	Pasadena	California	United States	91101
5	Stanford UniveritySchool of Medicine - Departmert of OB/GYN	Stanford	California	United States	94305
6	Genitourinary Surgical Consultants	Denver	Colorado	United States	80220
7	Mayo Clinic - Department of Urology	Jacksonville	Florida	United States	32224
8	University of Miami and Jackson Memorial Hospital	Miami	Florida	United States	33136
9	Specialists in Urology	Naples	Florida	United States	34102
10	Discovery Clinical Trials	Winter Haven	Florida	United States	33881
11	North Shore University Health System	Evanston	Illinois	United States	60201
12	Ochsner Clinic	New Orleans	Louisiana	United States	70121
13	LSU Health Science Center	New Orleans	Louisiana	United States	70122
14	Michigan Urology	Troy	Michigan	United States	48084
15	Northeast Urogynecology	Albany	New York	United States	12205
16	McKay Urology	Charlotte	North Carolina	United States	28207
17	The Urology Group	Cincinnati	Ohio	United States	45212
18	Midwest Institute for Research & Education	West Chester	Ohio	United States	45069
19	St. Lukes Hospital and Health Network	Allentown	Pennsylvania	United States	18104
20	Hospital for the University of Pennsylvannia - Penn Center for Continence and Public Health: Division of Urology	Philadelphia	Pennsylvania	United States	19104
21	Medical University of South Carolina - Department of Urology	Charleston	South Carolina	United States	29425
22	Urology Clinics of North Texas	Dallas	Texas	United States	75231
23	UT Southwestern Medical Center at Dallas - Department of Urology	Dallas	Texas	United States	75390
24	Vanguard Urologic Research Foundation	Houston	Texas	United States	77030
25	Urology San Antonio	San Antonio	Texas	United States	78229
26	Scott & White Memorial Hospital	Temple	Texas	United States	76508
27	University of Vermont - The Continence Center	Burlington	Vermont	United States	05403
28	Virgina Mason Medical Center - Section of Urology and Renal Transplantation	Seattle	Washington	United States	98101
29	Can-Med Clinical Research, Inc.	Victoria	British Columbia	Canada	V8T 5G1
30	Gary Steinhoff Clinical Research	Victoria	British Columbia	Canada	V8V3N1
31	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
32	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
33	University of Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
34	Hopital Tenon	Paris		France	75020

Sponsors and Collaborators

• Contura
• Regulatory and Clinical Research Institute (RCRI)

Investigators

• Study Director: Silvia Garcia-Codony, Contura

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Contura
• ClinicalTrials.gov Identifier: NCT00629083
• Other Study ID Numbers: CONSUI-US01
• First Posted: Mar 5, 2008
• Last Update Posted: Feb 7, 2020
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Contura: SUI; Bulkamid; Urinary Incontinence
• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Urinary Incontinence, Stress

Study Results

Participant Flow

Recruitment Details	The first subject was enrolled on June 4, 2008, and the last subject was enrolled on June 6, 2011. All participating study centers were in hospitals or clinics in the United States, Canada or France. The sites and investigators were qualified to treat stress urinary incontinence in women by experience and expertise.
Pre-assignment Detail	Pelvic Organ Prolapse Quantification, upright cystometry, Valsalva Leak Point Pressure, post-void residual measurement, daily number of incontinence episodes and a 24-hour pad test were completed prior to randomization to confirm eligibility in the trial.

Arm/Group Title	Bulkamid Hydrogel	Contigen Injection
Arm/Group Description	Bulkamid hydrogel is a proprietary, cross-linked polyacrylamide hydrogel developed for urethral bulking. The hydrogel consists of a backbone of cross-linked polyacrylamide, with water molecules loosely bound to the polymer matrix.	Contigen is a sterile non-pyrogenic implantable device composed of highly purified bovine dermal collagen that was lightly crosslinked with glutaraldehyde and dispersed in phosphate-buffered physiological saline
Period Title: Overall Study
STARTED	228	117
COMPLETED	200	103
NOT COMPLETED	28	14

Baseline Characteristics

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection	Total
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection	Total of all reporting groups
Overall Participants	228	117	345
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (11.4)	57.4 (14.3)	57.8 (12.4)
Sex: Female, Male (Count of Participants)
Female	228 100%	117 100%	345 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 9.6%	11 9.4%	33 9.6%
Not Hispanic or Latino	206 90.4%	106 90.6%	312 90.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.9%	1 0.9%	3 0.9%
Asian	4 1.8%	3 2.6%	7 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 0.9%	1 0.9%	3 0.9%
White	214 93.9%	109 93.2%	323 93.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 2.6%	3 2.6%	9 2.6%
Region of Enrollment (participants) [Number]
Canada	31 13.6%	15 12.8%	46 13.3%
United States	197 86.4%	102 87.2%	299 86.7%
Region of Enrollment (participants) [Number]
Canada	43 18.9%	21 17.9%	64 18.6%
United States	185 81.1%	96 82.1%	281 81.4%
24-hour Pad Test (g) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g]	93.6 (127.8)	115.4 (245.9)	104.5 (186.7)
Daily Number of Incontinence Episodes (number of daily episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of daily episodes]	4.1 (2.8)	3.5 (2.4)	3.8 (2.6)

Outcome Measures

1. Primary Outcome

Title	Primary Effectiveness Endpoint
Description	The number of subjects with at least a 50% reduction from baseline in both leakage, as measured by the 24h Pad Test, and daily number of incontinence episodes
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population.

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	228	117
Number [participants]	107 46.9%	50 42.7%

2. Primary Outcome

Title	The Number of Participants With Device- and Procedure-related Serious Adverse Events Through 12 Months Follow-up.
Description	The number of participants with device- and procedure-related serious adverse events through 12 months follow-up.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	228	117
Count of Participants [Participants]	1 0.4%	0 0%

3. Secondary Outcome

Title	24hr Pad Test
Description	A measure of urine leaked during a 24-hour period on a known weight and quantity of pads at the 12-month endpoint.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	186	94
Mean (Standard Deviation) [grams]	32.0 (64.2)	54.6 (120.3)

4. Secondary Outcome

Title	Number of Subjects Reporting as a Responder
Description	At the 12-month primary endpoint follow-up visit, the subject was asked to provide her perception of treatment effectiveness by circling the most accurate description of her condition: cured/dry; much improved; improved; no change; worse. The response was dichotomized into responder or non-responder. A subject was classified as a responder if she reported that the treatment had cured, much improved, or improved her incontinence condition.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	187	101
Count of Participants [Participants]	144 63.2%	71 60.7%

5. Secondary Outcome

Title	IQoL
Description	The IQoL is a validated instrument consisting of 22 questions grouped into three subscales: avoidance and limiting behaviors; psychosocial impacts, and social embarrassment. It is a subject self-reported quality-of-life measure specific to urinary problems that is used to assess the impact of urinary incontinence and urinary problems and their treatment. The subject scores each question on a scale of 1 to 5 with higher scores indicating more positive responses. The maximum score was 110 points and the minimum score was 22.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	198	103
Mean (Standard Deviation) [score on a scale]	80.3 (20.1)	75.2 (23.3)

6. Secondary Outcome

Title	ICIQ-UI Short Form
Description	The ICIQ-UI Short Form assesses the impact of symptoms of incontinence on quality of life and outcome of treatment. The questionnaire consists of three questions with a maximum score of 21 and a minimum score of zero (0). A lower score represents a decrease in the severity of symptoms (i.e., improvement).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).

Arm/Group Title	Bulkamid Hydrogel Injection	Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device	Contigen: Transurethral bulking injection
Measure Participants	196	102
Mean (Standard Deviation) [score on a scale]	7.1 (4.9)	7.9 (5.5)

7. Secondary Outcome

Title	Number of Incontinence Episodes
Description	The total number of incontinence episodes experienced by the subject over three consecutive days.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Complete Case (CC) analysis set.

Arm/Group Title	Treament	Control
Arm/Group Description	Bulkamid Hydrogel injection Bulkamid: Bulking injection with Bulkamid injection device	Contigen injection Contigen: Transurethral bulking injection
Measure Participants	195	101
Mean (Standard Deviation) [Episodes]	1.4 (1.7)	1.4 (1.9)

Adverse Events

Time Frame	Adverse event data were collected from each participant through her study completion visit, typically at 12 months.
Adverse Event Reporting Description	The definition of adverse event and/or serious adverse event used to collect adverse event information do not differ from the clinicaltrials.gov definitions.
Arm/Group Title	Bulkamid Hydrogel Injection		Contigen Injection
Arm/Group Description	Bulkamid: Bulking injection with Bulkamid injection device		Contigen: Transurethral bulking injection
All Cause Mortality
	Bulkamid Hydrogel Injection		Contigen Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/228 (0%)		0/117 (0%)
Serious Adverse Events
	Bulkamid Hydrogel Injection		Contigen Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/228 (2.2%)		0/117 (0%)
Gastrointestinal disorders
Gastrointestinal disorder	2/228 (0.9%)	3	0/117 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory disorder	3/228 (1.3%)	3	0/117 (0%)	0
Other (Not Including Serious) Adverse Events
	Bulkamid Hydrogel Injection		Contigen Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/228 (0%)		0/117 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.