Clinical trial NCT01789840: Prostate Artery Embolization With Embosphere Microspheres Compared to TURP for Benign Prostatic Hyperplasia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Benign Prostatic Hyperplasia
Keywords: BPH
Prostate
Prostatic Hyperplasia
enlarged prostate
LUTS
urinary retention
Lead sponsor: Merit Medical Systems, Inc.
Sponsor class: INDUSTRY
First posted: 2013-02-12
Enrollment: 59
Sex: MALE
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: International Prostate Symptom Score (IPSS) - Total Score at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: Duration of Hospitalization Post Procedure
timeFrame: 1 month
measure: Duration of Post Procedure Catheterization
timeFrame: 1 month
measure: Number of Adverse Events Per Patient
timeFrame: Through early termination of study (with less than 25% of subjects completing 12 month follow up)
measure: Number of Patients With Procedure Related Adverse Events
timeFrame: TEAEs at time of study termination, with less than 25% of subjects completing 12 month follow up
Other outcomes:
measure: Free Prostate Specific Antigen (PSA) at 6 Month Follow up
timeFrame: 6 month follow up
measure: Peak Urine Flow Rate (Qmax) at 1 Month
timeFrame: 1 month follow-up
measure: International Index of Erectile Function (IIEF)
timeFrame: 6 months
measure: Mean Prostate Volume, as Determined by MRI
timeFrame: 3 month follow-up
measure: Post-void Residual Urinary Volume (PVR)
timeFrame: 1 month follow-up
measure: Total Prostate Specific Antigen (PSA) at 6 Months
timeFrame: 6 months
Locations:
city: Long Beach
country: United States
facility: Long Beach VA
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Miami
country: United States
facility: Miami VA Healthcare System
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
Study officials:
affiliation: University of Sao Paolo, Brazil
name: Francisco, Cesar Carnevale, PhD
role: PRINCIPAL_INVESTIGATOR
References: