BPH With Symptomatic Lower Urinary Tract Symptoms
Conditions
Keywords
BPH / LUTS
Brief summary
A study to evaluate the safety, performance, and effectiveness of the ProVee Urethral Expander System (Investigational Device) when used in subjects with symptomatic urinary obstruction related to benign prostatic hyperplasia (BPH).
Detailed description
This is a prospective, multi-center, randomized, single-blind, sham-controlled study to evaluate the safety, performance, and effectiveness of the ProVee Urethral Expander System (Investigational Device) when used in subjects with symptomatic urinary obstruction related to benign prostatic hyperplasia (BPH). Subjects are assigned to their treatment arm using an unbalanced (2 ProVee:1 Sham) randomization stratified by Investigational Sites.
Interventions
ProVee Expander is placed in prostatic urethra to relieve obstruction due to BPH.
PROCEDUREUrethral Access Sheath
The Urethral Access Sheath is introduced into the prostatic urethra to simulate the placement of the ProVee Expander.
Sponsors
ProVerum Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subject will have noise cancelling headphones on during the treatment. A drape will be placed preventing subjects from observing implant procedure. The follow-up clinic coordinator will not have access to enrolled subjects' medical records including the randomization scheme and treatment procedure.
Intervention model description
Prospective, multi-center, randomized, double-blind, sham-controlled safety and effectiveness study
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males \> 45 years of age 2. IPSS of ≥ 13, IPSS V/S \> 1 at baseline assessment 3. Prostate volume of ≥ 30 cc and ≤ 80 cc 4. Prostatic urethral L2 lengths ≥ 3.75cm by TRUS 5. Failed, intolerant, or subject choice to not take a medication regimen for the treatment of LUTS
Exclusion criteria
1. Void volume \<125 ml; Qmax \> 12ml/s; PVR \> 250 ml 2. Obstructive median lobe defined by EITHER (\>10mm protrusion on sagittal mid-prostate plane as measured by TRUS) OR an obstructive median lobe seen on cystoscopy e.g., 'ball valve'' 3. High bladder neck, with the absence of lateral lobe encroachment indicating a high likelihood of primary bladder neck obstruction 4. Anatomy that would prevent the apices of the ProVee from engaging with the lateral lobes e.g., high degree of bladder neck angulation such that the anterior bladder neck is not visible 5. Acute urinary retention 6. Known immunosuppression 7. History of or suspected prostate or bladder cancer 8. Baseline PSA \> 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate cancer excluded to the Investigator's satisfaction, including a SOC biopsy if indicated). 9. Recent urinary tract stones, OR widespread calcifications on the prostatic urethral wall, within 3 months of index procedure 10. A history of prostatitis within the last two years 11. Active or history of epididymitis within the past 3 months 12. Neurogenic bladder and/or sphincter abnormalities due to Parkinson's disease, multiple sclerosis, cerebral vascular accident, diabetes' 13. History of urinary retention within 12 months of baseline assessment 14. Requiring self-catheterization to void 15. An active urinary tract infection (UTI) at time of index procedure 16. Gross haematuria, within 3 months of index procedure 17. Subjects with known allergy to nickel or titanium 18. Life expectancy estimated to be less than 60 months 19. Taking androgens, unless eugonadal state for at least 3 months or greater with a stable dosage for at least 2 months as documented by the Investigator 20. Use of 5-alpha-reductase inhibitors (e.g., dutasteride, finasteride) within 6 months of baseline assessment 21. Use of Phenylephrine / Pseudoephedrine within 24 hours of baseline assessment 22. Use of alpha-blockers (e.g., Terazosin, Doxazosin, Alfuzosin, Tamsulosin) within 2 weeks of baseline assessment 23. Use of estrogen or drug-producing androgen suppression (e.g. gonadotropin-releasing hormonal analogues) within 1 year of baseline assessment 24. Use of antihistamines, anticonvulsants, and antispasmodics within 1 week of baseline assessment unless there is documented evidence that the patient was on the same drug dose for at least 6 months with a stable voiding pattern (the drug dose should not be altered or discontinued for entrance into or throughout the study) 25. Use of anticholinergics or cholinergic medication within 2 weeks of baseline assessment 26. Use of beta-blockers where the dose is not stable. (Stable dose is defined as having the same medication and dose in the last 6 months) 27. Use of Phosphodiesterase-5 Enzyme Inhibitors in doses for BPH within 2 weeks of baseline assessment 28. Current treatment with anticoagulants (e.g., warfarin or enoxaparin) or antiplatelet medications other than aspirin (e.g., clopidogrel, or alternative and ASA). Patient unable to stop taking antiplatelet and/or antiplatelets within 3 days prior to the procedure or warfarin at least 5 days prior to the procedure. Low dose aspirin ≤100mg/day not prohibited 29. Future fertility concerns 30. Previous prostate surgery, balloon dilatation, stent implantation, laser prostatectomy, hyperthermia, or any other invasive treatment to the prostate; including penile implants 31. Previous pelvic irradiation or radical pelvic surgery 32. Previous rectal surgery (other than hemorrhoidectomy) or known history of rectal disease 33. Urethral strictures, bladder neck contracture, or other potentially confounding bladder pathology 34. Urethral pathologies that may prevent insertion of Delivery System 35. Uncontrolled diabetes mellitus including Hgb AIC \>8% 36. Overactive bladder (OAB) requiring treatment by OAB medication 37. Urinary incontinence 38. Patients taking tri-cyclic antidepressants. 39. Compromised renal function (i.e., serum creatinine \>1.8 mg/dl or upper tract disease) 40. Hepatic disorder, bleeding disorders or metabolic impairment that might confound the results of the study or have a risk to subject per investigator's opinion 41. Any major comorbidities or presence of unstable conditions, e.g., uncontrolled HTN, NYHA Class III or IV, cardiac arrhythmias that are not controlled by medication/medical device, myocardial infarction within the past 6 months, COPD with FEV1 \<50, renal illness that might prevent study completion or would confound study results 42. Vulnerable populations such as incarcerated or institutionalized adults, inmates, patients with physical, psychological (such as developmentally delayed adults), or medical impairment that might, in the judgment of the Investigator, prevent study completion or comprehension, or may confound study results (including patient questionnaires) 43. History or current medical condition that would result in an unacceptable patient risk if that subject were to be included in the study 44. Any subject that is currently enrolled in another ongoing investigational study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Events (Time Frame: Procedure to 12 Months) | Procedure - 12 months | This includes the rate of device or procedure related serious adverse events through 12-months. |
| Safety: Number of Participants With Need for Urinary Catheterization (Time Frame: >7 Days Post Procedure) | 7 days post treatment through to 12 months | The rate of extended post-operative urinary catheterization for inability to void among patients treated with the ProVee device. |
| Effectiveness: Number of Participants With Reduction in BPH Symptoms Compared to Sham (Time Frame: Procedure to 3 Months) | Procedure to 3 months | The ProVee Treatment Group will be considered superior to the Sham Treatment Group when the mean 3-month improvement from baseline score for the IPSS symptom questionnaire demonstrates a minimum statistical margin of 25% compared to mean improvement from baseline for the Sham Treatment Group alone. |
| Effectiveness: Number of Participants With Symptoms Improvements (Time Frame: Procedure to 12 Months) | Procedure to 12 months | The mean percent change in IPSS in the treatment arm is at least 30% improvement over the patient's pre-treatment baseline score. |
Countries
Canada, Ireland, United States
Participant flow
Recruitment details
All primary endpoint results are now entered. This Clinical Study Protocol and Statistical Analysis Plan has been redacted in accordance with the regulations at 42 CFR 11.48(a)(5). All SAEs reported have been adjudicated by CEC as not device or procedural related.
Participants by arm
| Arm | Count |
|---|---|
| Device: The ProVee Urethral Expander System The ProVee Urethral Expander System consists of two components: a nitinol Expander implant and a 19Fr Delivery System designed to allow the Expander to be deployed under direct vision for the treatment arm.
ProVee Urethral Expander System: ProVee Expander is placed in prostatic urethra to relieve obstruction due to BPH. | 150 |
| Sham: Ureteroscope and Urethral Access Sheath An ureteroscope housed within the inner lumen of an urethral access sheath will be used under direct vision for the Sham procedure.
Urethral Access Sheath: The Urethral Access Sheath is introduced into the prostatic urethra to simulate the placement of the ProVee Expander. | 71 |
| Total | 221 |
Baseline characteristics
| Characteristic | Device: The ProVee Urethral Expander System | Sham: Ureteroscope and Urethral Access Sheath | Total |
|---|---|---|---|
| Age, Customized Age | 64.0 Years STANDARD_DEVIATION 8.7 | 64.5 Years STANDARD_DEVIATION 8.2 | 64.2 Years STANDARD_DEVIATION 8.4 |
| BMI | 28.1 kg/m^2 STANDARD_DEVIATION 4.4 | 28.5 kg/m^2 STANDARD_DEVIATION 5.8 | 28.2 kg/m^2 STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 6 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 128 Participants | 63 Participants | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 137 Participants | 68 Participants | 205 Participants |
| Sex/Gender, Customized Male | 150 Participants | 71 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 150 | 0 / 71 | 0 / 64 |
| other Total, other adverse events | 1 / 150 | 0 / 71 | 0 / 64 |
| serious Total, serious adverse events | 8 / 150 | 0 / 71 | 0 / 64 |
Outcome results
Primary
Effectiveness: Number of Participants With Reduction in BPH Symptoms Compared to Sham (Time Frame: Procedure to 3 Months)
The ProVee Treatment Group will be considered superior to the Sham Treatment Group when the mean 3-month improvement from baseline score for the IPSS symptom questionnaire demonstrates a minimum statistical margin of 25% compared to mean improvement from baseline for the Sham Treatment Group alone.
Time frame: Procedure to 3 months
Population: Following the 3 month follow up, 64 subjects were crossed over from sham (ureteroscope and urethral access sheath) to device (the ProVee ureteral expander system)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device: The ProVee Urethral Expander System | Effectiveness: Number of Participants With Reduction in BPH Symptoms Compared to Sham (Time Frame: Procedure to 3 Months) | 0 Participants |
| Sham: Ureteroscope and Urethral Access Sheath | Effectiveness: Number of Participants With Reduction in BPH Symptoms Compared to Sham (Time Frame: Procedure to 3 Months) | 0 Participants |
| Crossover ProVee Urethral Expander System | Effectiveness: Number of Participants With Reduction in BPH Symptoms Compared to Sham (Time Frame: Procedure to 3 Months) | 0 Participants |
Primary
Effectiveness: Number of Participants With Symptoms Improvements (Time Frame: Procedure to 12 Months)
The mean percent change in IPSS in the treatment arm is at least 30% improvement over the patient's pre-treatment baseline score.
Time frame: Procedure to 12 months
Population: Following the 3 month follow up, 64 subjects from sham (ureteroscope and urethral access sheath) crossed over to device (the ProVee urethral expander system)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device: The ProVee Urethral Expander System | Effectiveness: Number of Participants With Symptoms Improvements (Time Frame: Procedure to 12 Months) | 0 Participants |
| Sham: Ureteroscope and Urethral Access Sheath | Effectiveness: Number of Participants With Symptoms Improvements (Time Frame: Procedure to 12 Months) | 0 Participants |
| Crossover ProVee Urethral Expander System | Effectiveness: Number of Participants With Symptoms Improvements (Time Frame: Procedure to 12 Months) | 0 Participants |
Primary
Safety: Number of Device or Procedure Related Serious Adverse Events (Time Frame: Procedure to 12 Months)
This includes the rate of device or procedure related serious adverse events
Time frame: Procedure - 12 months
Population: At 3 month follow-up visit, 64 subjects were crossed over from Sham (Uretheroscope and urethral access sheath) to Device (The ProVee Urethral Expander System)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device: The ProVee Urethral Expander System | Safety: Number of Device or Procedure Related Serious Adverse Events (Time Frame: Procedure to 12 Months) | 0 Participants |
| Sham: Ureteroscope and Urethral Access Sheath | Safety: Number of Device or Procedure Related Serious Adverse Events (Time Frame: Procedure to 12 Months) | 0 Participants |
| Crossover ProVee Urethral Expander System | Safety: Number of Device or Procedure Related Serious Adverse Events (Time Frame: Procedure to 12 Months) | 0 Participants |
Primary
Safety: Number of Participants With Need for Urinary Catheterization (Time Frame: >7 Days Post Procedure)
The rate of extended post-operative urinary catheterization for inability to void among patients treated with the ProVee device.
Time frame: 7 days post treatment through to 12 months
Population: At 3-month follow up, 64 subject were crossed over from Sham (Ureteroscope and Urethral Access Sheath) to Device (The ProVee Urethral Expander System).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Device: The ProVee Urethral Expander System | Safety: Number of Participants With Need for Urinary Catheterization (Time Frame: >7 Days Post Procedure) | 0 Participants |
| Sham: Ureteroscope and Urethral Access Sheath | Safety: Number of Participants With Need for Urinary Catheterization (Time Frame: >7 Days Post Procedure) | 0 Participants |
| Crossover ProVee Urethral Expander System | Safety: Number of Participants With Need for Urinary Catheterization (Time Frame: >7 Days Post Procedure) | 0 Participants |