Prostate Artery Embolization With Embosphere Microspheres Compared to TURP for Benign Prostatic Hyperplasia

Prospective, Controlled Investigation of Prostate Artery Embolization With Embosphere Microspheres Compared to Transurethral Resection of the Prostate for the Treatment of Symptomatic Benign Prostatic Hyperplasia

The purpose of this study is to evaluate improvement of symptoms from benign prostatic hyperplasia (BPH) as assessed by the International Prostate Symptom Score (IPSS) for prostatic artery embolization (PAE) using Embosphere Microspheres compared to conventional transurethral resection of the prostate (TURP).

The study will consist of a screening period in which patient eligibility will be determined and baseline assessments performed. Once eligibility is confirmed, patients will be enrolled within 4 weeks of baseline imaging to receive either TURP or PAE with Embosphere Microspheres. After treatment, patients will return for follow-up visits at Months 1, 3, 6, and 12. At each of these visits patients will complete IPSS and IIEF questionnaires and have a physical exam, laboratory assessments (including PSA), a DRE, and a transrectal ultrasound of the prostate. At each visit patients will have a cystoscopy and proctoscopy if medically indicated. Cystoscopy is necessary in all cases of hematuria (injury associated with bleeding). Proctoscopy is necessary in all cases of bleeding per the rectum. An MRI of the prostate will be conducted at the 3 and 12 month visits. Uroflowmetry testing will be performed at the 1 and 12 month visits, and at other visits if medically indicated. MRIs will be assessed by blinded Central Reviewers.

The primary endpoint will be improvement of symptoms from BPH evaluated using the IPSS at 12 months post treatment. Patients will continue to be followed annually for up to 4 additional years. At a minimum, patients will be requested to complete the IPSS and International Index of Erectile Dysfunction (IIEF) questionnaires by telephone, email or mail once per year during this long term follow up period. Patients who are willing to return to the clinic will have a physical exam, MRI of the prostate, digital rectal exam (DRE), transrectal ultrasound of the prostate, PSA, and uroflowmetry testing performed each year. Treatments for LUTS due to BPH after the study treatment and 12 month follow up are complete will be documented during the long term follow up period to the extent possible. This long term follow up data will be summarized and submitted separately from the data for the initial 12 months of this study.

Safety will be evaluated throughout the initial 12 months of the study by assessing adverse events, as well as changes in laboratory values, and findings on physical examination. Concomitant medication usage will be assessed. A follow up ECG will be performed at the 12 month visit.

Patient recruitment is anticipated to take approximately 2 years. Duration of each patient's participation is expected to be 5 years, including a 4 year long term follow up period. The total duration of the study will be approximately 7 years, including long term follow up.

Inclusion Criteria:

1. Patient is age 50 to 79, inclusive

2. Patient has signed informed consent

3. Patient has had lower urinary tract symptoms (LUTS) secondary to BPH for at least 6 months prior to study treatment

4. Patient has a baseline IPSS Score > 13 at baseline

5. Patient has a prostate size of at least 50 grams and not more than 90 grams, measured by MRI

6. Patient has BPH symptoms refractory to medical treatment or for whom medication is contraindicated, not tolerated or refused

7. Patient must be a candidate for TURP

8. Patient must meet one of the following criteria:

   • Baseline Prostate Specific Antigen (PSA) <2.5 ng/mL (no prostate biopsy required)
   • Baseline PSA >2.5 ng/mL and ≤10 ng/mL AND free PSA > 25% of total PSA (no prostate biopsy required)
   • Baseline PSA >2.5 ng/mL and ≤10 ng/mL AND free PSA < 25% of total PSA AND a negative prostate biopsy result (minimum 12 core biopsy)
   • Baseline PSA >10 ng/mL AND a negative prostate biopsy (minimum 12 core biopsy)

Exclusion Criteria:

1. Active urinary tract infection

2. Biopsy proven prostate or bladder cancer, or any cancer other than basal or squamous cell skin cancer

   • The following patients must undergo prostate biopsy with a minimum of 12 cores and have a negative histopathology report to be enrolled in the study:

     • Patients with digital rectal examination (DRE) findings suspicious for prostate cancer
     • Patients with baseline PSA levels > 10 ng/mL
     • Patients with baseline PSA levels >2.5 ng/mL and < 10ng/mL AND free PSA < 25% of total PSA

   • Patients with cystoscopy findings suspicious for bladder cancer must undergo biopsy and have a negative histopathology report to be enrolled in the study

3. Bladder atonia, neurogenic bladder disorder or other neurological disorder that is impacting bladder function (eg multiple sclerosis, Parkinson's disease, spinal cord injuries, etc)

4. Urethral stricture, bladder neck contracture, sphincter abnormalities, urinary obstruction due to causes other than BPH, or other potentially confounding bladder or urethral disease or condition

5. Patient has taken beta blockers, antihistamines, anticonvulsants, or antispasmodics within 1 week of study treatment AND has not been on the same drug dosage for 6 months with a stable voiding pattern

   • Dosage of these medications should not change during study participation unless medically necessary

6. Patient has taken antidepressants, anticholinergics, androgens or gonadotropin-releasing hormonal analogues within 2 months of study treatment AND has not been on the same drug dosage for at least 3 months with a stable voiding pattern

7. Patient has taken 5-alpha reductase inhibitors or alpha blockers within 1 month of study treatment AND has not been on the same drug dosage for at least 3 months with a stable voiding pattern

8. Previous non-medical BPH treatment, including surgery, TURP, needle ablation, microwave or laser therapy, balloon dilation, stent implantation, or any other invasive treatment to the prostate

9. Any known condition that limits catheter-based intervention or is a contraindication to embolization, such as intolerance to a vessel occlusion procedure or severe atherosclerosis.

10. Patient is unable to stop taking anticoagulant, nonsteroidal antiinflammatory drug (NSAID) or anti-platelet therapy for 7 days prior to study treatment

11. Unable to have MRI imaging (eg metal implant including pacemaker, replacement joint, etc)

12. Patient has an asymmetric prostate, with > 20% difference in size between lobes

13. Cardiac condition including congestive heart failure or arrhythmia, uncontrolled diabetes mellitus, significant respiratory disease or known immunosuppression which required hospitalization within the previous 6 months

14. Baseline serum creatinine level > 1.8 mg/dl

15. Known upper tract renal disease

16. Cystolithiasis or chronic hematuria within 3 months prior to study treatment

17. Active prostatitis

18. Previous rectal surgery other than hemorrhoidectomy, or history of rectal disease

19. History of pelvic irradiation or radical pelvic surgery

20. Patient is interested in future fertility

21. Coagulation disturbances not normalized by medical treatment

22. Acute urinary retention requiring an indwelling catheter

23. Known major iliac arterial occlusive disease

24. Allergy to iodinated contrast agents

25. Hypersensitivity to gelatin products