Stress Urinary Incontinence
Conditions
Keywords
SUI, Bulkamid, Urinary Incontinence
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
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.
Interventions
Sponsors
Regulatory and Clinical Research Institute Inc
Contura
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Number of Incontinence Episodes | 12 months | The total number of incontinence episodes experienced by the subject over three consecutive days. |
| 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). |
| 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. |
Countries
Canada, France, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Bulkamid Hydrogel Injection Bulkamid: Bulking injection with Bulkamid injection device | 228 |
| Contigen Injection Contigen: Transurethral bulking injection | 117 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 12 | 8 |
| Overall Study | Moved out of country/state | 2 | 1 |
| Overall Study | Refused to return for 12 month visit | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Bulkamid Hydrogel Injection | Contigen Injection | Total |
|---|---|---|---|
| 24-hour Pad Test | 93.6 g STANDARD_DEVIATION 127.8 | 115.4 g STANDARD_DEVIATION 245.9 | 104.5 g STANDARD_DEVIATION 186.7 |
| Age, Continuous | 58.0 years STANDARD_DEVIATION 11.4 | 57.4 years STANDARD_DEVIATION 14.3 | 57.8 years STANDARD_DEVIATION 12.4 |
| Daily Number of Incontinence Episodes | 4.1 number of daily episodes STANDARD_DEVIATION 2.8 | 3.5 number of daily episodes STANDARD_DEVIATION 2.4 | 3.8 number of daily episodes STANDARD_DEVIATION 2.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 11 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 206 Participants | 106 Participants | 312 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 214 Participants | 109 Participants | 323 Participants |
| Region of Enrollment Canada | 43 participants | 21 participants | 64 participants |
| Region of Enrollment United States | 185 participants | 96 participants | 281 participants |
| Sex: Female, Male Female | 228 Participants | 117 Participants | 345 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 228 | 0 / 117 |
| other Total, other adverse events | 0 / 228 | 0 / 117 |
| serious Total, serious adverse events | 5 / 228 | 0 / 117 |
Outcome results
Primary
Primary Effectiveness Endpoint
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
Population: Intent-to-treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bulkamid Hydrogel Injection | Primary Effectiveness Endpoint | 107 participants |
| Contigen Injection | Primary Effectiveness Endpoint | 50 participants |
Primary
The Number of Participants With Device- and Procedure-related Serious Adverse Events Through 12 Months Follow-up.
The number of participants with device- and procedure-related serious adverse events through 12 months follow-up.
Time frame: 12 months
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bulkamid Hydrogel Injection | The Number of Participants With Device- and Procedure-related Serious Adverse Events Through 12 Months Follow-up. | 1 Participants |
| Contigen Injection | The Number of Participants With Device- and Procedure-related Serious Adverse Events Through 12 Months Follow-up. | 0 Participants |
Secondary
24hr Pad Test
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
Population: Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bulkamid Hydrogel Injection | 24hr Pad Test | 32.0 grams | Standard Deviation 64.2 |
| Contigen Injection | 24hr Pad Test | 54.6 grams | Standard Deviation 120.3 |
Secondary
ICIQ-UI Short Form
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
Population: Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bulkamid Hydrogel Injection | ICIQ-UI Short Form | 7.1 score on a scale | Standard Deviation 4.9 |
| Contigen Injection | ICIQ-UI Short Form | 7.9 score on a scale | Standard Deviation 5.5 |
Secondary
IQoL
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
Population: Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bulkamid Hydrogel Injection | IQoL | 80.3 score on a scale | Standard Deviation 20.1 |
| Contigen Injection | IQoL | 75.2 score on a scale | Standard Deviation 23.3 |
Secondary
Number of Incontinence Episodes
The total number of incontinence episodes experienced by the subject over three consecutive days.
Time frame: 12 months
Population: This analysis was performed on the Complete Case (CC) analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bulkamid Hydrogel Injection | Number of Incontinence Episodes | 1.4 Episodes | Standard Deviation 1.7 |
| Contigen Injection | Number of Incontinence Episodes | 1.4 Episodes | Standard Deviation 1.9 |
Secondary
Number of Subjects Reporting as a Responder
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
Population: Complete Case (CC): Randomized subjects with complete data for a specific endpoint at a particular time point (no imputed data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bulkamid Hydrogel Injection | Number of Subjects Reporting as a Responder | 144 Participants |
| Contigen Injection | Number of Subjects Reporting as a Responder | 71 Participants |