Rezum I Pilot Study for Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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Evaluate the safety and efficacy of the Rezum System for the treatment of BPH

Detailed Description
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Prospective, non-randomized clinical trial of subjects with benign prostatic hyperplasia. The objective of the study are to 1) determine the safety and efficacy of the BPH Rezum System and assess its effect on urinary symptoms secondary to benign prostatic hyperplasia (BPH), and 2) further document the safety and post-operative effects of the Rezum System in the treatment of obstructive BPH.

Official Title
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NxThera Benign Prostatic Hyperplasia Rezum System Pilot Study

Conditions
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Prostatic Hyperplasia, Benign Prostatic Hyperplasia, Adenoma, Prostatic, Prostatic Adenoma, Prostatic Hyperplasia, Benign, Prostatic Hypertrophy, Prostatic Hypertrophy, Benign, Rezum

Intervention / Treatment
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* Device: Rezum System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects > 45 years of age who have symptomatic / obstructive symptoms secondary to BPH requiring invasive intervention. IPSS score of ≥ 15. Qmax: Peak flow rate ≤ 15 ml/sec. Post-void residual (PVR) < 300 ml. Prostate transverse diameter > 30 mm. Prostate volume between 20 to 120 gm. Voided volume ≥ 125 mL Subject able to complete the study protocol in the opinion of the investigator. Life expectancy of at least one year. Exclusion Criteria: History of any illness or surgery that may confound the results of the study or have risk to subject. Presence of a penile implant. Any prior minimally invasive intervention (e.g. TUNA, Balloon, Microwave) or surgical intervention for the symptoms of BPH. Currently enrolled or has been enrolled in another trial in the past 30 days. Confirmed or suspected malignancy of prostate or bladder Previous rectal surgery (other than hemorrhoidectomy) or history of rectal disease. Previous pelvic irradiation or radical pelvic surgery. Documented active urinary tract infection by culture or bacterial prostatitis within last year documented by culture (UTI is defined as >100,000 colonies per ml urine from midstream clean catch or catherization specimen) Neurogenic bladder or sphincter abnormalities. Urethral strictures, bladder neck contracture or muscle spasms. Bleeding disorder or is currently on coumadin. (Note that use of anti-platelet medication is not an exclusion criteria.) Subjects interested in maintaining fertility. Use of concomitant medications to include the following: Use of, antihistamines, and antispasmodics within 1 week of treatment unless there is documented evidence stable dosing for last 6 months (no dose changes). Use of alpha blockers, androgens, or gonadotropin-releasing hormonal analogs within 2 weeks of treatment. Use of 5-alpha reductase inhibitor within the last 6 months Use of antidepressants, anticholinergics, anticonvulsants, and beta blockers unless there is documented evidence of stable dosing Subject is unable or unwilling to go through the washout period prior to treatment. Subject has chronic urinary retention. Post-void residual volume > 300 ml. Significant urge incontinence. Poor detrusor muscle function. Neurological disorders which might affect bladder or sphincter function. Urinary sphincter abnormalities. Bladder stones. Evidence of bacterial prostatitis or symptoms of epididymitis Renal impairment or serum creatinine > 2.0 mg/dl In the physician's opinion, subject cannot tolerate a cystoscopy procedure well. Unable or unwilling to sign the Informed Consent Form (ICF) and/or comply with all the required follow-up requirements. Any cognitive disorder that interferes with or precludes direct and accurate communication with the study investigator regarding the study. Peripheral arterial disease with intermittent claudication or Leriches Syndrome (i.e., claudication of the buttocks or perineum). Biopsy of prostate within 30 days of procedure.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rezum Treatment<br>Patients received the Rezum transurethral needle ablation procedure to treat benign prostatic hyperplasia. | Device: Rezum System<br>* The Rezūm System treats patients with bothersome urinary symptoms associated with benign prostatic hyperplasia (BPH). The Rezūm System utilizes radiofrequency current to generate wet thermal energy in the form of water vapor, which is then injected into the transition zone and/or median lobe of the prostate tissue in controlled 9-second doses. The vapor that is injected into the prostate tissue rapidly disperses through the interstitial space between the tissue cells. As the vapor cools, it condenses immediately on contact with tissue and the stored thermal energy is released, denaturing the cell membranes and causing cell death. The denatured cells are absorbed by the body, which reduces the volume of prostate tissue adjacent to the urethra. The vapor condensation process also causes a rapid collapse of vasculature in the treatment zone, resulting in a bloodless procedure.<br>* Other names: Rezum Generator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Prostate Symptom Score (IPSS) Change From Baseline | International Prostate Symptom Score (IPSS) scores were recorded at Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, then annually to 5 years. The mean change (improvement) in IPSS was calculated. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Improvement in symptoms is shown by a reduction in score. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Major Complications | Safety assessed by the frequency of systemic and local serious device related complications and the occurrence of unanticipated device-related adverse effects during treatment and at follow-up, up to 30 days. Due to the nature of the device, any device-related AEs are expected to present themselves during the immediate peri-procedure period (30 days post procedure). The device related complications that will be compared for this safety endpoint are: Severe Urinary Retention (Retention ≥ 24 hours) Fistula between rectum and urethra Perforation of the rectum or GI tract New incidences of retrograde ejaculation | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Responders - Responders With a ≥ 30% International Prostate Symptom Score (IPSS) Improvement | The proportion of study subjects who were responders were evaluated. A responder is defined as a subject with ≥ 30% improvement in BPH symptoms from baseline as measured by the IPSS. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Proportion of Responders - Responders With a ≥ 50% International Prostate Symptom Score (IPSS) Improvement | The proportion of study subjects who were responders were evaluated. For this measure a responder is defined as a subject with ≥ 50% improvement in BPH symptoms from baseline as measured by the IPSS. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Proportion of Responders - Responders With Improvement ≥ 8 Points in IPSS | Analysis will be provided for proportion of subjects with improvement ≥ 8 points from baseline at 1 week, 1 month, and 3 months, 6 months, 1 year, annually to 5 years | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Uroflow Assessment - Change From Baseline in Peak Urinary Flow (Qmax) | Peak urinary flow rate (Qmax) is the maximum urinary flow rate. It is calculated as milliliters (ml) of urine passed per second. Average results are based on age and sex. Typical uroflow rates ranges from 10 ml to 21 ml per second. An increase in mL/sec corresponds to improved urinary function. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Uroflow Assessment - Proportion of Subjects With Qmax Improvement of ≥ 30% From Baseline | Peak urinary flow rate (Qmax) is the maximum urinary flow rate. It is calculated as milliliters (ml) of urine passed per second. This measure reports the number of subjects who experienced a ≥ 30% improvement from baseline at each follow-up interval. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Uroflow Assessment - Proportion of Subjects With Qmax Improvement of ≥ 3 ml/Sec | Peak urinary flow rate (Qmax) is the maximum urinary flow rate. It is calculated as milliliters (ml) of urine passed per second. This measure reports the number of subjects who experienced a ≥3 mL/sec improvement from baseline at each follow-up interval. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Uroflow Assessment - Change in Post Void Residual (PVR) by Follow up Interval | Change in post void residual (PVR) urine volume in ml. Post void residual volume was measured by either ultrasound to measure the volume left in the bladder after urination, or by inserting a urinary catheter into the bladder after urination to drain and measure residual urine. Either measurement tool was allowed but the same measurement was to be used pre and post treatment. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Change in Sexual Function - Erectile Function | Change from baseline in sexual function was measured by the International Index of Erectile Function (IIEF) (Scoring on the IIEF ranges from 1 to 30. An increase in score indicates improvement from baseline) | 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Change in Sexual Function - Retrograde Ejaculation | Rate of Retrograde Ejaculation (when no fluid exits the penis during orgasm (e.g., dry orgasm) | 1 Week post procedure, 1 Month post procedure, 3 Months post procedure | 
| International Prostate Symptom Score (IPSS) Assessment by Prostate Volume | International Prostate Symptom Score (IPSS) scores were recorded at Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, then annually to 5 years. The mean change in IPSS was calculated. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Mean change in IPSS scores reported at each follow-up interval. Improvement in symptoms is shown by a reduction in score. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| International Prostate Symptom Score (IPSS) Assessment Based on Prostate Lobe Treated: Lateral Only vs. Lateral and Median Lobe | International Prostate Symptom Score (IPSS) scores were recorded at Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, then annually to 5 years. The mean change in IPSS was calculated. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Mean change in IPSS scores reported at each follow-up interval. Improvement in symptoms is shown by a reduction in score. Results report change in IPSS by follow up interval for subjects treated in both lateral lobes and median lobe vs. subjects treated in lateral lobes alone. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| International Prostate Symptom Score (IPSS) Assessment Based on Baseline IPSS | International Prostate Symptom Score (IPSS) scores were recorded at Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, then annually to 5 years. The mean change in IPSS was calculated. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Mean change in IPSS scores reported at each follow-up interval and grouped by Baseline IPSS. Improvement in symptoms is shown by a reduction in score. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, annually to 5 years | 
| Procedural Pain Score | Pain scores were obtained for all subjects using the Iowa Pain Thermometer. Maximum intraprocedural pain scores were analyzed, together with the pain scores reported at follow-up intervals through 3 months. The treatment pain scores were reported by subjects post-procedure and was based on their recollections. Scale is 0-12 with higher scores corresponding to higher pain reported. | Day of treatment, 1 Day post procedure, 1 Week post procedure, 1 Month post procedure, 3 Months post procedure | 
| Quality of Life (QoL) - Change in QoL as Measured With the International Prostate Symptom Score (IPSS) | Change in Quality of Life was measured using a QoL question in the IPSS. QoL data were collected at each follow up visit. One question in the IPSS asked subjects to rate their quality of life due to urinary symptoms on a scale of 0 = Delighted to 6 = Terrible. A reduction in score from baseline equates to improved outcome. | Baseline to 1 week, 1 month, 3 months, 6 months, 1 year, then annually to 5 years | 
| Quality of Life (QoL) - Change in QoL as Measured With the Benign Prostatic Hyperplasia Impact Index (BPHII) | Change in Quality of Life will be measured with the Benign Prostatic Hyperplasia Impact Index (BPHII). Data were collected at specified follow up visits. BPHII scores range from 0 (no/mild symptoms) to 35 (severe symptoms). A reduction in score from baseline equates to an improvement in symptoms. | Baseline to 1 month, 3 months, 6 months, 1 year, then annually to 5 years | 
| Quality of Life (QoL) - Change in QoL as Measured With the EQ-5D-3L | Quality of Life was measured using EQ-5D-3L questionnaire. QoL data were collected at each follow up visit. The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to all subjects to assess the effect of the treatment on the subjects' quality of life. EQ-5D-3L index ranges from -0.109 to 1.000, with 1.000 corresponding to the best health state and -0.109 corresponding to the worst health. Mean change in overall score from baseline is reported. | 1 month, 3 months, 6 months, 1 year, then annually to 5 years | 
| Quality of Life (QoL) - Change in QoL as Measured With the EQ-5D-3L Visual Analog Scale (VAS) | Quality of Life was measured using EQ-5D-3L questionnaire and collected at each follow up visit. The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to all subjects to assess the effect of the treatment on the subjects' quality of life. The EQ-5D-3L includes a visual analog scale (VAS) which is a vertical scale with numbers ranging from 0 to 100. Subjects were asked to draw a line to the place on the scale that best represented how good or bad his health was on that day. The worst state a subject can imagine is marked zero, and the best state the subject can imagine is marked 100. Mean change in VAS score from baseline is reported. An increase in score is considered a better outcome. | 1 month, 3 months, 6 months, 1 year, then annually to 5 years | 
| Quality of Life (QoL) - QoL Dimensions as Measured With the EQ-5D-3L | Quality of Life was measured using EQ-5D-3L questionnaire. QoL data were collected at each follow up visit. The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to all subjects to assess the effect of the treatment on the subjects' quality of life. Each dimension had 3 possible responses (1 =no problem, 2 =some problem 3 =severe problems) in the relevant health dimension. Presented below are the scoring counts for each of the dimensions for baseline and follow up interval. | 1 month, 3 months, 6 months, 1 year, then annually to 5 years | 
| Subject Satisfaction - Satisfied With Overall Procedure | Subject satisfaction assessed using a study specific questionnaire to evaluate the subject's overall satisfaction of the procedure at 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years. These will be measured as: • Proportion of subjects that are satisfied with the procedure overall Note: Subject Satisfaction Questionnaire is specific to the NxThera Rezūm treatment and 3 of the 7 questions were used to evaluate the subjects' overall satisfaction with the procedure. Within the questionnaire, subjects sometimes did not answer all of the questions, which resulted in a different n by question within the same follow-up time point. | 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years | 
| Subject Satisfaction - Proportion of Subjects Who Would Recommend Procedure to Friends and Family | Subject satisfaction assessed using a study specific questionnaire to evaluate the subject's overall satisfaction of the procedure at 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years. Outcome measured as: • Proportion of subjects that would recommend this treatment to friends and families Note: Subject Satisfaction Questionnaire is specific to the NxThera Rezūm treatment and 3 of the 7 questions were used to evaluate the subjects' overall satisfaction with the procedure. Within the questionnaire, subjects sometimes did not answer all of the questions, which resulted in a different n by question within the same follow-up time point. | 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years | 
| Subject Satisfaction - Proportion of Subjects Who Would Undergo Same Treatment if Symptoms Were to Recur After 5 Years | Subject satisfaction assessed using a study specific questionnaire to evaluate the subject's overall satisfaction of the procedure at 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years. Outcome measured as: • Proportion of subjects who would undergo the same treatment if their symptoms were to recur after 5 years Note: Subject Satisfaction Questionnaire is specific to the NxThera Rezūm treatment and 3 of the 7 questions were used to evaluate the subjects' overall satisfaction with the procedure. Within the questionnaire, subjects sometimes did not answer all of the questions, which resulted in a different n by question within the same follow-up time point. | 1 week, 1 month, 3 months, 6 months, 1 year, and annually to 5 years | 
| Procedural Parameters - Procedure Time | Procedure time: Time from delivery device insertion to final delivery device withdrawal | Day of Procedure | 
| Procedural Parameters - Treatment Time | Treatment time: time from first vapor delivery to last vapor delivery | Day of Procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rezum, Water Vapor Ablation