Safety and Efficacy Study for the Treatment of BPH (Enlarged Prostate)

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and efficacy of the Rezūm System and assess its effect on urinary symptoms secondary to benign prostatic hyperplasia (BPH).

Detailed Description
-----------------
This study is a prospective, controlled, randomized single blind clinical trial of subjects with benign prostatic hyperplasia, which will allow for an interim analysis for sample size adjustment. Subjects first will be randomized in a 2:1 proportion in favor of the Treatment arm. Subjects in the Control arm will be allowed to crossover to have the Rezūm treatment after the 3-month follow-up examination.

Official Title
-----------------
Minimally Invasive Prostatic Vapor Ablation - Multicenter, Controlled Study for the Treatment of BPH (Rezūm II)

Conditions
-----------------
Benign Prostatic Hyperplasia, Lower Urinary Tract Symptom

Intervention / Treatment
-----------------
* Device: Rezum System
* Procedure: Rigid Cystoscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male subjects > 50 years of age who have symptomatic BPH. International Prostate Symptom Score (IPSS) score ≥ 13. Peak urinary flow rate (Qmax): ≥ 5ml/sec to ≤ 15 ml/sec with minimum voided volume of ≥ 125 ml. Post-void residual (PVR) ≤250 ml. Prostate volume > 30 and ≤ 80 gm. Exclusion Criteria: History of clinically significant congestive heart failure (i.e. NYHA Class III and IV). History of diabetes not controlled by a stable dose of medication over the past three months. Patients with a Hemoglobin A1c that is <8.0% are allowed. History of significant respiratory disease where hospitalization for the disease is required. History of immunosuppressive conditions (e.g., AIDS, post-transplant). Cardiac arrhythmias that are not controlled by medication or medical device. An episode of unstable angina pectoris, a myocardial infarction, transient ischemic attack, or a cerebrovascular accident within the past six months. Any significant medical history that would pose an unreasonable risk or make the subject unsuitable for the study. Presence of a penile implant or stent(s) in the urethra or prostate. Any prior invasive prostate intervention (e.g., radio frequency (RF) ablation, balloon, microwave, or laser) or other surgical interventions of the prostate. Currently enrolled in any other pre-approval investigational study in the USA (does not apply to long-term post-market studies unless these studies might clinically interfere with the current study endpoints (e.g., limit use of study-required medication, etc.)). History of confirmed malignancy or cancer of prostate or bladder, however, high grade PIN is acceptable. History of cancer in non-genitourinary system that is not considered cured (except basal cell or squamous cell carcinoma of the skin). A potential participant is considered cured if there has been no evidence of cancer within five years of randomization. Previous pelvic irradiation or radical pelvic surgery. Diagnosed with active Lyme Disease (borreliosis). PSA > 10 ng/ml unless prostate cancer is ruled out by biopsy. If PSA is > 2.5 ng/ml and ≤ 10 ng/ml with free PSA <25%, prostate cancer for the subject must be/had been ruled out through a negative biopsy prior to enrollment. Has undergone prostate biopsy within 60 days prior to treatment date or has an imminent need for surgery. Previous rectal surgery (other than hemorrhoidectomy) or known history of rectal disease. Active urinary tract infection by culture within 7 days of treatment or two documented independent urinary tract infections of any type in the past 6 months. Verified bacterial prostatitis within last 12 months documented by culture or non-bacterial prostatitis within the last 5 years. Active or history of epididymitis within the past 3 months. Neurogenic bladder, sphincter abnormalities, or poor detrusor muscle function. 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. Urethral strictures, bladder neck contracture, unusual anatomy or muscle spasms that would prevent the introduction and use of the device. Diagnosed bladder, urethral or ureteral stones or active stone passage in the past 6 months. Stones that are known to be in the kidney and have been stable for a period exceeding 3 months are permissible. Post-void residual (PVR) > 250 ml. Diagnosed or suspected bleeding disorder, or coagulopathies. Use of antiplatelet or anticoagulant medication except low dose aspirin (≤81 mg/day) within 10 days prior to treatment. Visible hematuria with subject urine sample without a known contributing factor. Subject interested in maintaining fertility. Use of beta-blockers, anticonvulsants, and antispasmodics where the dose is not stable. (Stable dose is defined as having the same medication and dose in the last six months). At the time of baseline assessment, in the absence of a qualifying exception, subjects who are using or have used the following medications, and are unable or unwilling to discontinue using these medications for the prescribed washout period: Use of antihistamines within 1 week of treatment unless there is documented evidence of stable dosing for last 6 months (no dose changes). Use of the alpha blockers for BPH and anticholinergics or cholinergics (except for topical anti cholinergic eye drops), or within 4 weeks of baseline assessment. Use of Type II, 5-alpha reductase inhibitor (e.g., finasteride (Proscar, Propecia) within 3 months of baseline assessment. Use of a dual 5-alpha reductase inhibitor (e.g., dutasteride (Avodart)) within 6 months of baseline assessment. Use of estrogen, drug-producing androgen suppression, or anabolic steroids within 3 months of baseline assessment. Use of daily dose PD5 Inhibitors (e.g.Viagra, Levitra or Cialis) within 4 weeks of baseline assessment. Subjects who have had an incidence of spontaneous urinary retention either treated with indwelling transurethral catheter or suprapubic catheter six months prior to baseline. A provoked episode now resolved is still admissible. Compromised renal function defined as serum creatinine > 2.0 mg/dl. Inability to provide a legally effective Informed Consent Form (ICF) and/or comply with all the required follow-up requirements. 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.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treatment: Rezūm System | Device: Rezum System<br>* The Rezūm System uses sterile water vapor (steam) to treat BPH by delivering targeted, controlled doses of stored thermal energy directly to the transition zone of the prostate gland. A narrow sheath, similar in shape and size to a cystoscope, is inserted transurethrally and positioned within the prostatic urethra between the bladder neck and the verumontanum. A thin needle is deployed through the urethra into the transition zone, and a very short (8-10 second) treatment of water vapor is delivered directly into the hyperplastic tissue and immediately disperses through the tissue interstices. Upon contact with the tissue, the vapor condenses, or phase shifts, into its liquid state, releasing the stored thermal energy contained within the vapor. This thermal energy is released directly against the walls of the tissue cells within the treatment zone, gently and immediately denaturing the cell membranes, thereby causing instantaneous cell death.<br>|
| Other: Control<br>Control: Rigid Cystoscopy | Procedure: Rigid Cystoscopy<br>* Endoscopy of the urinary bladder via the urethra.<br>* Other names: Cystoscopy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Change From Baseline in the International Prostate Symptom Score (IPSS) at 3 Month Follow-Up | Comparison of the change in BPH symptoms as measured by IPSS change between the Treatment and Control arm at 3 months post-treatment. The IPSS is a well-validated, highly reliable and responsive American Urological Association symptom score (AUASS) assessment to identify the severity of BPH Symptoms. The first seven questions of the IPSS Questionnaire address frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency each on a scale of 0 to 5. The total score, summed across the seven items measured, ranges from 0 (no symptoms) to 35 (most severe symptoms). | 3 Month Follow-up Visit | 
| Safety: Device Related Serious Complications | This safety endpoint will be to demonstrate that the composite observed rate of post-procedure device related serious complications in the Treatment Arm are is less than or equal to 12% at 3 months. Composite device related serious complications for this endpoint are 1) De Novo (new) severe urinary retention lasting more than 21 consecutive days post treatment, 2) Device related formation of fistula between the rectum and urethra, and 3) device perforation of the rectum or GI tract. Twelve percent was a pre-specified performance goal for the safety endpoint. | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responders at 3 Months | Number of subjects with a greater than or equal to 30% improvement (reduction) in the International Prostate Symptom score (IPSS) at 3 months compared to baseline. | 3 Months | 
| Responders at 6 Months | Number of subjects with a greater than or equal to 30% improvement (reduction) in the International Prostate Symptom score (IPSS) at 6 months compared to baseline. | 6 Months | 
| Responders at 12 Months | Number of subjects with a greater than or equal to 30% improvement (reduction) in the International Prostate Symptom score (IPSS) at 12 months compared to baseline. | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hyperplasia, Retention, Prostate