Urethral Stricture
Conditions
Keywords
pivotal trial, randomized, lower urinary tract symptoms (LUTS), urethral stricture, obstruction
Brief summary
ROBUST III is a prospective, multi-center, randomized controlled adaptive sample size clinical trial to establish the safety and effectiveness for the Optilume Stricture Drug Coated Balloon (DCB).
Detailed description
ROBUST III is a prospective, multi-center, single blind randomized controlled clinical trial in a 2:1 allocation of treatment versus control device. This study is an adaptive design with an interim analysis for sample size re-estimation performed after 60 subjects have been enrolled. The interim analysis will be be undertaken following completion of the 6-month follow-up data from these subjects. Based on the results of the interim analysis, the final total sample size required for the study will be re-estimated. A minimum of 140 subjects, and a maximum of 200 subjects (pending the re-estimation) will be enrolled in the study. A Data Monitoring Committee (DMC) will review the interim analysis results, including the sample size re-estimation and make recommendations related to trial continuation to the sponsor.
Interventions
DEVICEControl Treatment
A control subject may be dilated with either a rod, uncoated balloon or DVIU until the desired result is reached, based on standard of care for the clinical site and treating physician
DEVICEOptilume Drug Coated Balloon (DCB)
The Optilume Drug Coated Balloon (DCB) is a guidewire compatible catheter with a tapered atraumatic tip. The distal end of the catheter has an inflatable balloon coated with a proprietary coating containing the drug paclitaxel that facilitates the drug's transfer to the urethral wall upon inflation.
Sponsors
Laborie Medical Technologies Inc.
NAMSA
Urotronic Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male subjects ≥ 18 years' old 2. Visual confirmation of stricture via cystoscopy or urethrogram 3. Single, tandem or diffuse anterior urethral stricture(s), less than or equal to 3.0 cm total length measured by retrograde urethrogram. (Stricture length is defined as the distance between the most distal edge of the stricture to the most proximal edge of the stricture). 4. Two or more prior dilation treatments of the same stricture, including DVIU (Direct Vision Internal Urethrotomy), but no prior urethroplasty. 5. Significant symptoms of stricture such as frequency of urination, dysuria, urgency, hematuria, slow flow, feeling of incomplete emptying, recurrent urinary tract infections (UTI's). 6. International Prostrate Symptoms Score (IPSS) score of 11 or higher (assumed to be 35 if suprapubic catheter is present) 7. Lumen diameter ≤ 12F by urethrogram 8. Qmax \<15 ml/sec (assumed to be 0 if suprapubic catheter is present) 9. Guidewire must be able to cross the lesion
Exclusion criteria
1. Subjects with diffuse stricture length, greater than 3.0 cm in total length. (Stricture length is defined as the distance between the most distal edge of the stricture to the most proximal edge of the stricture). 2. Subjects with a history of hypersensitivity reactions to TAXOL, on medication that may have negative interaction with paclitaxel, with solid tumors who have a baseline neutrophil counts of \<1500 cells/mm3 or subjects with AIDS-related Kaposi's sarcoma with baseline neutrophile counts of \<1000 cells/mm3. 3. Subjects who had an indwelling suprapubic catheter longer than three (3) months total prior to enrollment. 4. Previous urethroplasty within the anterior urethra 5. Stricture dilated or incised within the last six (6) weeks (urethral catheterization is not considered dilation) 6. Presence of local adverse factors, including abnormal prostate making catheterization difficult, urethral false passage or fistula. 7. Presence of signs of obstructive voiding symptoms not directly attributable to the stricture at the discretion of the physician 8. Diagnosis of untreated and unresolved BPH or BNC 9. Untreated stress urinary incontinence (SUI). 10. History of diagnosed radiation cystitis. 11. Diagnosis of carcinoma of the urethra, bladder or prostate within the last two (2) years 12. Active kidney, bladder, urethral or ureteral stone passage in the last six (6) weeks or concern of stone passage in the next 6 weeks at the discretion of the investigator. 13. Diagnosis of chronic renal failure and treatment with hemodialysis 14. New diagnosis of OAB (overactive bladder) within the last six (6) months 15. Use of alpha blockers, beta blockers, OAB (Overactive Bladder) medication, anticonvulsants (drugs that prevent or reduce the severity and frequency of seizures), and antispasmodics where the dose is not stable. (Stable dose is defined as having the same medication and dose in the last six months.) 16. Dependence on Botox (onabotulinumtoxinA) in urinary system 17. Presence of an artificial urinary sphincter, slings, or stent(s) in the urethra or prostate 18. Known neurogenic bladder, sphincter abnormalities, or poor detrusor muscle function 19. Diagnosed with Lichen Sclerosus, or stricture due to balanitis xerotica obliterans (BXO) 20. Previous hypospadias repair 21. 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 two (2) years of enrollment 22. Any cognitive or psychiatric condition that interferes with or precludes direct and accurate communication with the study investigator regarding the study or affect the ability to complete the study quality of life questionnaires 23. Unwilling to use protected sex for thirty (30) days' post treatment 24. Unwilling to abstain or use protected sex for ninety (90) days post treatment if sexual partner is of child bearing potential. 25. Inability to provide Informed Consent Form (ICF) and/or comply with all the required follow-up requirements 26. Participation in other pre-market studies or treatment with an investigational drug or device. Long term follow up or post market study of an approved device is allowed. 27. Current active infection in the urinary system 28. Current uncontrolled diabetes (hemoglobin A1c \> 8.0%) or evidence of poor wound healing due to diabetes 29. Diagnosed or suspected primary neurologic conditions such as multiple sclerosis or Parkinson's disease or other neurological diseases known to affect bladder function, sphincter function or poor detrusor muscle function. 30. Visible hematuria in subject's urine sample without known contributing factor 31. Invisible hematuria (or significant microscopic hematuria, i.e. hematuria of ≥ 3 RBC's/HPF) that may be caused by a clinically significant disease unless it is attributed to the urethral stricture disease or other causes which are benign and not requiring treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Stricture Free | 6 months | The percentage of subjects deemed to be stricture free will be compared between arms. Stricture free subjects are those for which a 16F flexible cystoscope or 14F Foley catheter is able to be passed through the treated stricture without significant resistance. |
| Safety: Rate of Major Device or Procedure Related Complications | 3 months | Rate of Major Device or Procedure Related complications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Qmax (Peak Flow Rate) | 6 months | Change in peak urinary flow rate (Qmax) from baseline to 6 months post treatment. Positive values indicate an increase in Qmax from baseline to 6 months, while negative values indicate a decrease in Qmax. |
| IPSS Percent Responder (50% Improvement in IPSS Score) | 12 months | The proportion of subjects considered to be therapeutic responders, defined as an improvement of greater than or equal to 50% in the International Prostate Symptom Score \[IPSS\] without repeat intervention, in the Optilume DCB arm at 12 months will be compared to a performance goal of 50%. The IPSS was developed to measure symptom severity for bladder outlet obstruction, with a range of 0 (no symptoms) to 35 (worst possible symptoms). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Optilume Treatment The treatment arm will be the Urotronic Optilume Drug Coated Balloon (DCB).
Optilume Drug Coated Balloon (DCB): The Optilume Drug Coated Balloon (DCB) is a guidewire compatible catheter with a tapered atraumatic tip. The distal end of the catheter has an inflatable balloon coated with a proprietary coating containing the drug paclitaxel that facilitates the drug's transfer to the urethral wall upon inflation. | 79 |
| Control Treatment The control arm will be treated by a urethral dilation method considered to be best standard of care for the study site and subject. A control treatment may be either a rod, uncoated balloon or DVIU.
Control Treatment: A control subject may be dilated with either a rod, uncoated balloon or DVIU until the desired result is reached, based on standard of care for the clinical site and treating physician | 48 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 6 | 26 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Optilume Treatment | Control Treatment | Total |
|---|---|---|---|
| Age, Continuous | 58.7 Years STANDARD_DEVIATION 15.5 | 60.6 Years STANDARD_DEVIATION 16 | 59.4 Years STANDARD_DEVIATION 15.7 |
| Anatomic Stricture Location Bulbar Urethra | 71 Participants | 45 Participants | 116 Participants |
| Anatomic Stricture Location Penile Urethra | 8 Participants | 2 Participants | 10 Participants |
| Anatomic Stricture Location Unknown | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 45 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Prior Dilations | 3.0 Dilations STANDARD_DEVIATION 1.73 | 3.0 Dilations STANDARD_DEVIATION 7.7 | 3.0 Dilations STANDARD_DEVIATION 4.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 65 Participants | 39 Participants | 104 Participants |
| Region of Enrollment Canada | 4 participants | 2 participants | 6 participants |
| Region of Enrollment United States | 75 participants | 46 participants | 121 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 79 Participants | 48 Participants | 127 Participants |
| Stricture Etiology Iatrogenic | 21 Participants | 16 Participants | 37 Participants |
| Stricture Etiology Idiopathic | 42 Participants | 22 Participants | 64 Participants |
| Stricture Etiology Inflammatory | 1 Participants | 2 Participants | 3 Participants |
| Stricture Etiology Traumatic | 14 Participants | 7 Participants | 21 Participants |
| Stricture Etiology Unknown | 1 Participants | 1 Participants | 2 Participants |
| Stricture Length | 1.63 cm STANDARD_DEVIATION 0.76 | 1.72 cm STANDARD_DEVIATION 0.73 | 1.67 cm STANDARD_DEVIATION 0.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 79 | 0 / 48 |
| other Total, other adverse events | 51 / 79 | 38 / 48 |
| serious Total, serious adverse events | 9 / 79 | 8 / 48 |
Outcome results
Primary
Percentage of Subjects Stricture Free
The percentage of subjects deemed to be stricture free will be compared between arms. Stricture free subjects are those for which a 16F flexible cystoscope or 14F Foley catheter is able to be passed through the treated stricture without significant resistance.
Time frame: 6 months
Population: Only subjects with cystoscopy completed at 6 month visit or with known repeat intervention were included in this analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Optilume Treatment | Percentage of Subjects Stricture Free | 50 Participants |
| Control Treatment | Percentage of Subjects Stricture Free | 11 Participants |
p-value: <0.0001Chi-squared, Corrected
Primary
Safety: Rate of Major Device or Procedure Related Complications
Rate of Major Device or Procedure Related complications
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Optilume Treatment | Safety: Rate of Major Device or Procedure Related Complications | 0 Participants |
| Control Treatment | Safety: Rate of Major Device or Procedure Related Complications | 0 Participants |
Secondary
Change in Qmax (Peak Flow Rate)
Change in peak urinary flow rate (Qmax) from baseline to 6 months post treatment. Positive values indicate an increase in Qmax from baseline to 6 months, while negative values indicate a decrease in Qmax.
Time frame: 6 months
Population: Patients with a measured Qmax at baseline and 6 months. Subjects that underwent repeat treatment for a recurrent stricture had the last observed Qmax value prior to repeat treatment utilized (worst case imputation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Optilume Treatment | Change in Qmax (Peak Flow Rate) | 8.8 mL/Sec | Standard Deviation 9.2 |
| Control Treatment | Change in Qmax (Peak Flow Rate) | 4.1 mL/Sec | Standard Deviation 7.2 |
p-value: 0.003t-test, 2 sided
Secondary
IPSS Percent Responder (50% Improvement in IPSS Score)
The proportion of subjects considered to be therapeutic responders, defined as an improvement of greater than or equal to 50% in the International Prostate Symptom Score \[IPSS\] without repeat intervention, in the Optilume DCB arm at 12 months will be compared to a performance goal of 50%. The IPSS was developed to measure symptom severity for bladder outlet obstruction, with a range of 0 (no symptoms) to 35 (worst possible symptoms).
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Optilume Treatment | IPSS Percent Responder (50% Improvement in IPSS Score) | 39 Participants |