Benign Prostatic Hyperplasia
Conditions
Keywords
BPH, Drug Coated Balloon, DCB, prostate, LUTS, Optilume
Brief summary
PINNACLE is a prospective, multi-center, randomized control clinical trial to establish the safety and efficacy of the Optilume™ BPH Catheter System in the treatment of benign prostatic hyperplasia (BPH)
Detailed description
This is a prospective, multi-center, double blind, randomized controlled clinical trial in a 2:1 allocation of Test versus sham Control. In addition, a single arm of 15 non-randomized subjects will be added to study the Pharmacokinetics of the drug. The objectives of the study are to assess the efficacy of Optilume BPH Catheter System to alleviate LUTS believed to be secondary to BPH (LUTS/BPH) and to evaluate the safety of Optilume BPH Catheter System in the treatment of LUTS/BPH.
Interventions
DEVICEOptilume BPH Catheter System
The Optilume™ BPH, Prostatic Dilation DCB Catheter is a dilation catheter used to exert radial force to dilate the prostatic urethra resulting in a commissurotomy. The distal end of the catheter has a semi-compliant inflatable double lobe balloon that is coated with a proprietary coating containing the active pharmaceutical paclitaxel.
DEVICEOptilume Sham Device
21 Fr sheathed Optilume™ BPH Prostatic Pre-dilation Catheter (modified to prevent inflation)
Sponsors
Urotronic Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Subjects in the Randomization arm of the study are randomized in a 2:1 allocation of Test to Control. The treating physician is unblinded to the treatment assignment. A blinded person at the study site conducts all study follow-up visits through the 12-Month follow-up visit (or until the subject is unblinded). The subject may be unblinded prior to the 12-Month visit if it is medically necessary, which includes the subject seeking alternative BPH therapy due to continued or recurrent BPH symptoms.
Intervention model description
Randomized study with a non-randomized, Pharmacokinetics arm. Subjects randomized to the Control arm are allowed to crossover to the Test arm if they meet the eligibility criteria after completing the 3-Month Follow-up Visit and prior to the close of the 12-Month visit window. Up to 625 subjects will be enrolled (i.e. consented) in the study in order to identify 162 eligible subjects (147 randomized subjects and 15 Pharmacokinetic subjects)
Eligibility
Sex/Gender
MALE
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male subject 50-80 years of age who has symptomatic BPH 2. International Prostate Symptom Score (IPSS) ≥ 13 3. Peak urinary flow rate (Qmax) ≥ 5 ml/sec and ≤ 12 ml/sec (with minimum voided volume of ≥ 150 ml) 4. Prostate volume 20 to 80 gm as determined by transrectal ultrasound (TRUS) 5. Prostatic urethral length ≥ 32 mm and ≤ 55 mm as determined by TRUS 6. History of inadequate response, contraindication, or refusal of BPH medical therapy 7. Able to complete the study protocol in the opinion of the investigator
Exclusion criteria
1. Unable or unwilling to sign the Informed Consent Form (ICF) and/or comply with all the follow-up requirements 2. Unwilling to abstain or use protected sex for the first 30 days post treatment 3. Unwilling to abstain from sexual intercourse or use a highly effective contraceptive for at least 6 months post-procedure 4. Presence of an artificial urinary sphincter or stent(s) in the urethra or prostate 5. Any prior minimally invasive intervention (e.g. TUNA, Balloon, Microwave, Rezūm, UroLift) or surgical intervention of the prostate 6. Prostate specific antigen (PSA) ≥ 10 ng/ml unless prostate cancer is ruled out by biopsy 7. Confirmed or suspected malignancy of prostate or bladder 8. Active or history of epididymitis within the past 3 months 9. Previous pelvic irradiation or pelvic trauma surgery 10. Active urinary tract infection (UTI) confirmed by culture 11. Bacterial prostatitis within the last 12 months 12. Non-bacterial prostatitis within the last 5 years 13. Visible or invisible hematuria (\> 4 Red Blood Cells (RBCs) per high power field) on 2 separate urine specimens within the last 3 months without a know contributing factor 14. Neurogenic bladder or sphincter abnormalities or neurological disorders that might affect bladder or sphincter function 15. History of urinary incontinence 16. Previous or current diagnosis of urethral strictures, bladder neck contracture or detrusor muscle spasms 17. Previous rectal surgery, other than hemorrhoidectomy 18. Use of antihistamines, anticonvulsants or antispasmodics within 1 week prior to baseline assessment unless there is documented evidence of stable dosing for at least 6 months 19. Use of antidepressants with adrenergic effects (i.e. duloxetine, imipramine and amitriptyline), long-acting anticholinergics (LAAC) for chronic obstructive pulmonary disease (COPD), or androgens within 2 weeks prior to baseline assessment unless there is documented evidence of stable dosing for at least 3 months prior to baseline assessment 20. Use of Luteinizing Hormone-Releasing Hormone (LHRH) analogs within 12 months prior to baseline assessment 21. Use of Type II 5-alpha reductase inhibitor \[e.g. finasteride (Proscar, Propecia)\] within 3 months of baseline assessment 22. Use of 5-alpha reductase inhibitor \[e.g. dutasteride (Avodart)\] within 6 months of baseline assessment 23. Use of estrogen or drugs producing androgen suppression unless there is documented evidence of stable dosing for at least 3 months prior to baseline assessment 24. Use of alpha blockers or daily dose PDE5 inhibitor (e.g. Cialis) within 2 weeks of baseline assessment 25. Use of warfarin or novel oral anti-coagulants \[e.g., apixaban (Eliquis), fondaparinux (Arixtra), rivaroxaban (Xarelto) or edoxaban (Savaysa)\], unless the medication is safely discontinued prior to the procedure and is not planned to be restarted for at least 5 days post-procedure 26. Use of anti-platelet medications (e.g., clopidogrel, aspirin) within 10 days prior to the procedure or planned use within 5 days post-procedure 27. History of hypersensitivity reactions to paclitaxel, on medication that may have negative interaction with paclitaxel, presence of solid tumor with a baseline neutrophil count of \<1500 cells/mm3 or AIDS-related Kaposi's sarcoma with baseline neutrophil count of \<1000 cells/mm3 28. Incidence of spontaneous urinary retention within 6 months prior to baseline assessment 29. Current post-void residual volume \> 300 ml or catheter dependent bladder drainage 30. Known poor detrusor muscle function (e.g. Qmax \< 5 ml/sec) 31. Current bladder or prostatic urethral stones 32. Biopsy of prostate within 40 days prior to procedure 33. History of cancer in non-genitourinary system which is not considered in complete remission (except basal cell or squamous cell carcinoma of the skin). A potential participant is considered in complete remission if there has been no evidence of cancer within five years 34. Current uncontrolled diabetes (i.e. hemoglobin A1c ≥ 8%) 35. History of clinically significant comorbidities or presence of unstable conditions \[e.g. cardiovascular, lung, renal (serum creatinine \> 2.0 mg/dl), hepatic, bleeding disorders or metabolic impairment\] that may confound the results of the study or have a risk to subject per investigator's opinion 36. Any cognitive disorder that interferes with or precludes direct and accurate communication with the study investigator regarding the study or affects the ability to complete the study quality of life questionnaires 37. Life expectancy \< 10 years 38. Anatomy (e.g. presence of false passage or size of meatus) is not suitable for treatment in this study 39. Significant median lobe component \[e.g. intravesical prostatic protrusion (IPP) \> 1 cm\] 40. Device that corresponds with the subject's prostate size is not available 41. Currently enrolled in or plan to enroll in another investigational clinical study for any disease except for observational only study 42. In the opinion of the investigator, it is not in the subject's best interest to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With >30% Improvement in the International Prostate Symptom Score (IPSS) | 12 months | The primary efficacy endpoint was the improvement in International Prostate Symptom Score (IPSS) at 12 months in the Optilume BPH arm compared to the improvement in IPSS at 3 months in the Sham arm with a super-superiority margin on 25%. The IPSS contains the well-validated, highly reliable and responsive American Urological Association symptom score (AUASS) assessment to identify the severity of BPH symptoms. The first seven questions in the IPSS address frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, and urgency, and scored on a 6-point scale (0 to 5). The IPSS can be interpreted as follows: 0-7 mildly symptomatic, 8-19 moderately symptomatic, and 20-35 severely symptomatic. The IPSS also includes an eighth question that is designed to assess the degree of "bother" associated with the subject's urinary symptoms. Answers range from "delighted" to "terrible" (0-6). This question is not included in the calculation of the main IPSS score. |
| Number of Participants With Major Device Related Serious Complications | 12 months | Rate of major device-related serious complications. A major device-related serious complication is defined as any of the following events through 12 months: * Device-related rectal fistula or GI fistula * Device-related formation of fistula between the rectum and urethra * Device-related new onset severe urinary retention lasting \> 14 consecutive days post-healing * Device-related unresolved new onset stress urinary incontinence by 90 days * Device-related bleeding requiring transfusion * Device-related urethra or prostatic capsule rupture requiring surgical intervention |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORSteven A Kaplan, MD
Mount Sinai Health System
Participant flow
Recruitment details
162 subjects will be randomized and/or treated in the study at up to 30 clinical sites in the United States and Canada. Up to 625 subjects will be enrolled (i.e. consented) in the study in order to identify 162 eligible subjects to be randomized and/or treated. All subjects treated with the Optilume BPH Catheter System will be followed annually through 5 years. Study duration is approximately 8 years.
Pre-assignment details
Any required procedures performed before obtaining informed consent as part of the standard of care may be used in lieu of the study tests. Subjects who require a washout period should have these evaluations, with the exception of informed consent, conducted following completion of the washout period. Subjects who cannot tolerate a drug washout or are considered high risk from the drug washout should be excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Optilume™ BPH Catheter System The Optilume™ BPH, Prostatic Dilation DCB Catheter is a dilation catheter used to exert radial force to dilate the prostatic urethra resulting in a commissurotomy. The distal end of the catheter has a semi-compliant inflatable double lobe balloon that is coated with a proprietary coating containing the active pharmaceutical paclitaxel.
Optilume BPH Catheter System: The Optilume™ BPH, Prostatic Dilation DCB Catheter is a dilation catheter used to exert radial force to dilate the prostatic urethra resulting in a commissurotomy. The distal end of the catheter has a semi-compliant inflatable double lobe balloon that is coated with a proprietary coating containing the active pharmaceutical paclitaxel. | 100 |
| Sham Device The Sham Device is a 21 Fr Optilume BPH, Prostatic Pre-dilation Catheter within the sheath.
Optilume Sham Device: 21 Fr sheathed Optilume™ BPH Prostatic Pre-dilation Catheter (modified to prevent inflation) | 48 |
| Pharmacokinetic (PK) Arm A single arm of 14 non-randomized subjects will be treated in the pharmacokinetics (PK) arm.
The Optilume™ BPH, Prostatic Dilation DCB Catheter is a dilation catheter used to exert radial force to dilate the prostatic urethra resulting in a commissurotomy. | 14 |
| Total | 162 |
Baseline characteristics
| Characteristic | Optilume™ BPH Catheter System | Sham Device | Pharmacokinetic (PK) Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 64.5 Years STANDARD_DEVIATION 6.4 | 65.5 Years STANDARD_DEVIATION 5.6 | 65.6 Years STANDARD_DEVIATION 7.4 | 64.8 Years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 3 Participants | 0 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 45 Participants | 14 Participants | 146 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| International Prostate Symptom Score (IPSS) | 23.4 score STANDARD_DEVIATION 5.5 | 24.3 score STANDARD_DEVIATION 5.8 | 22.7 score STANDARD_DEVIATION 4.2 | 23.75 score STANDARD_DEVIATION 5.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 94 Participants | 43 Participants | 12 Participants | 149 Participants |
| Region of Enrollment Canada | 6 participants | 2 participants | 0 participants | 8 participants |
| Region of Enrollment United States | 94 participants | 46 participants | 14 participants | 154 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 98 Participants | 48 Participants | 14 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 98 | 0 / 48 | 0 / 25 | 0 / 14 |
| other Total, other adverse events | 81 / 98 | 14 / 48 | 15 / 25 | 10 / 14 |
| serious Total, serious adverse events | 14 / 98 | 3 / 48 | 0 / 25 | 0 / 14 |
Outcome results
Primary
Number of Participants With >30% Improvement in the International Prostate Symptom Score (IPSS)
The primary efficacy endpoint was the improvement in International Prostate Symptom Score (IPSS) at 12 months in the Optilume BPH arm compared to the improvement in IPSS at 3 months in the Sham arm with a super-superiority margin on 25%. The IPSS contains the well-validated, highly reliable and responsive American Urological Association symptom score (AUASS) assessment to identify the severity of BPH symptoms. The first seven questions in the IPSS address frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, and urgency, and scored on a 6-point scale (0 to 5). The IPSS can be interpreted as follows: 0-7 mildly symptomatic, 8-19 moderately symptomatic, and 20-35 severely symptomatic. The IPSS also includes an eighth question that is designed to assess the degree of bother associated with the subject's urinary symptoms. Answers range from delighted to terrible (0-6). This question is not included in the calculation of the main IPSS score.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Optilume™ BPH Catheter System | Number of Participants With >30% Improvement in the International Prostate Symptom Score (IPSS) | 89 Participants |
| Sham Device | Number of Participants With >30% Improvement in the International Prostate Symptom Score (IPSS) | 26 Participants |
Primary
Number of Participants With Major Device Related Serious Complications
Rate of major device-related serious complications. A major device-related serious complication is defined as any of the following events through 12 months: * Device-related rectal fistula or GI fistula * Device-related formation of fistula between the rectum and urethra * Device-related new onset severe urinary retention lasting \> 14 consecutive days post-healing * Device-related unresolved new onset stress urinary incontinence by 90 days * Device-related bleeding requiring transfusion * Device-related urethra or prostatic capsule rupture requiring surgical intervention
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Optilume™ BPH Catheter System | Number of Participants With Major Device Related Serious Complications | 89 Participants |
| Sham Device | Number of Participants With Major Device Related Serious Complications | 26 Participants |