Minimally Invasive Prostatic Vapor Ablation for the Treatment of BPH in Large Prostates (Rezūm XL)

A prospective, multicenter, single arm clinical trial designed to evaluate the safety of the Rezūm System in treating subjects with symptomatic BPH for prostate sizes >80cm3 and ≤150 cm3.

• Prostatic Vapor Ablation (Device), also known as Rezum, Water Vapor Ablation: Rezūm uses the stored thermal energy in water vapor (steam) to treat the extra prostate tissue that is causing symptoms such as frequency, urgency, irregular flow, weak stream, straining and getting up at night to urinate. Inside a hand-held device, radiofrequency energy is applied to a few drops of water to create vapor (steam). The water vapor is injected into the prostate tissue that is blocking the flow of urine from the bladder, where it immediately turns back to water, releasing the energy stored in the vapor into the cell membranes. At this point, the cells are gently and immediately damaged, causing cell death. Over time, the body absorbs the treated tissue through its natural healing response.

Primary outcomes

• Number of Participants With ≥ 30% Improvement in Symptoms as Measured by the International Prostate Symptom Score (IPSS) [6 Months]: The proportion of the intent-to-treat (ITT) analysis population that responds to the Rezum therapy is reported. A responder is defined as a subject who has an improvement in International Prostate Symptom Score (IPSS) > 30% from baseline to 6 months post-therapy. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Improvement in symptoms is shown by a reduction in score.
• Number of Participants With Post Procedure Device Related Serious Complications [6 Months]: Assess the composite rate of post procedure device related serious complications in treated subjects through 6 months follow-up.

Secondary outcomes

• Number of Subjects With Device-related Retention Catheterizations [6 Month]: This safety endpoint will be to characterize the rate of post procedure device-related serious retention catheterizations at 6 months.
• Change in Lower Urinary Tract Symptoms as Assessed by the Absolute Change in IPSS Score From Baseline to Follow-up [Baseline, 6 weeks, 3 months, 6 months, 1 year]: The change in IPSS from baseline to each follow-up visit was determined. IPSS scores range from 0 (no symptoms) to 35 (severe symptoms). Improvement in symptoms is shown by a reduction in score.

Sex: Male, ages: 50 Years to any

Inclusion Criteria:

1. Male subjects ≥ 50 years of age who have symptomatic BPH.
2. International Prostate Symptom Score (IPSS) score ≥ 13.
3. Peak urinary flow rate (Qmax): ≥ 5ml/sec to ≤ 12 ml/sec with minimum voided volume of ≥ 125 ml.
4. Post-void residual (PVR) ≤300 ml.
5. Prostate volume >80 cm3 to ≤150 cm3

Exclusion Criteria:

Urology:

1. Any prior invasive prostate intervention (e.g., "Radiofrequency" thermotherapy, balloon, microwave thermotherapy, "Prostatic Urethral Lift", "Transurethral Resection", or laser) or other surgical interventions of the prostate.
2. Undergone a prostate biopsy within 60 days prior to the scheduled treatment date or has an imminent need for surgery.
3. Verified acute bacterial prostatitis within last 12 months documented by culture.
4. Active or history of epididymitis within the past 3 months.
5. Urethral strictures, bladder neck contracture, unusual anatomy or muscle spasms that would prevent the introduction and use of the Rezūm device.
6. Diagnosed bladder, urethral or ureteral stones or active stone passage in the past 6 months, provided that stones that are known to be in the kidney and have been stable for a period exceeding 3 months are permissible.
7. Subject interested in maintaining fertility.
8. Use of the following medications where the dose is not stable (stable dose defined as the same medication and dose in the last three months):

   1. Beta-blockers;
   2. Anticonvulsants;
   3. Antispasmodics;
   4. Antihistamines;
   5. Alpha blockers for BPH and anticholinergics or cholinergics;
   6. Type II, 5-alpha reductase inhibitor (e.g., finasteride (Proscar, Propecia));
   7. Dual 5-alpha reductase inhibitor (e.g., dutasteride (Avodart));
   8. Estrogen, drug-producing androgen suppression, or anabolic steroids;
   9. PD5 Inhibitors (e.g., Viagra, Levitra or Cialis)
9. Subjects who have had an incidence of spontaneous urinary retention either treated with indwelling transurethral catheter or suprapubic catheter 6 months prior to baseline. A provoked episode now resolved is still admissible
10. Evidence of atonic neurogenic bladder evaluated by a baseline urodynamic assessment.
11. Visible hematuria with subject urine sample without a known contributing factor.
12. Presence of a penile implant or stent(s) in the urethra or prostate
13. 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.

    Gastroenterology:
14. Previous pelvic irradiation or radical pelvic surgery.
15. Previous rectal surgery (other than hemorrhoidectomy) or known history of rectal disease.

    Nephrology:
16. Compromised renal function defined as serum creatinine > 2.0 mg/dl.
17. Hydronephrosis (Grade 2 or higher).

    Oncology:
18. Prostate cancer testing:

    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
    * Males 50-59 years - PSA is >2.5 ng/ml and ≤10 ng/ml with free PSA <25%,
    * Males 60+ years - PSA is >4 ng/ml and ≤10 ng/ml, with free PSA <25%
19. History of confirmed malignancy or cancer of the prostate or bladder; however, high grade prostatic intraepithelial "PIN" is acceptable.
20. 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 enrollment.

    Cardiology:
21. History of clinically significant congestive heart failure (i.e., NYHA Class III and IV).
22. Cardiac arrhythmias that are not controlled by medication and/or medical device.
23. An episode of unstable angina pectoris, a myocardial infarction, transient ischemic attack, or a cerebrovascular accident within the past six months.

    Pulmonology:
24. History of significant respiratory disease where hospitalization for the disease is required.

    Hematology:
25. Diagnosed or suspected bleeding disorder, or coagulopathies.
26. Use of antiplatelet or anticoagulant medication except low dose aspirin (<100mg/day) within 10 days prior to treatment.

    Endocrinology:
27. History of diabetes not controlled by a stable dose of medication over the past three months, provided that patients with a hemoglobin A1c <8.0% are allowed.

    Immunology:
28. History of immunosuppressive conditions (e.g., AIDS, post-transplant).

    Neurology:
29. 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.
30. 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 (< 25% of accepted and established nomograms).

    General:
31. Currently enrolled in any other pre-approval investigational study in the US (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.).
32. Any significant medical history that would pose an unreasonable risk or make the subject unsuitable for the study.
33. Inability to provide a legally effective "Informed Consent Form" and/or comply with all the required follow-up requirements.

Participant flow

Outcome results

• Number of Participants With ≥ 30% Improvement in Symptoms as Measured by the International Prostate Symptom Score (IPSS) (Primary), Count of participants, Participants: Treatment 39
• Number of Participants With Post Procedure Device Related Serious Complications (Primary), Count of participants, Participants: Treatment 0
• Number of Subjects With Device-related Retention Catheterizations (Secondary), Count of participants, Participants: Treatment 0
• Change in Lower Urinary Tract Symptoms as Assessed by the Absolute Change in IPSS Score From Baseline to Follow-up (Secondary), Mean, score on a scale: Treatment -8.47 (-10.49 to -6.45)

Adverse events

Time frame: Adverse events were collected from the first patient in until the termination of the study. All 47 subjects were followed to at least the 6- month follow-up visit.

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The study was terminated by the sponsor for business reasons. As a result there is no patient data presented for the 12 month, 2 year and 3 year follow up visits as they did not occur per termination.

• Study Protocol and Statistical Analysis Plan (PDF, 2018-10-01)

• Henry Woo, MD, Principal investigator, Sydney Adventist Hospital