Prostate Artery Embolization as a Treatment for Benign Prostatic Hyperplasia in Men With Prostates Larger Than 90 Grams

Phase II, Single Center, Single Arm, Open Label Investigation of Prostate Artery Embolization as a Treatment for Benign Prostatic Hyperplasia in Men With Prostates Larger Than 90 Grams

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02396420

Enrollment

Registered

2015-03-24

Start date

2015-09-24

Completion date

2016-11-17

Last updated

2018-11-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostatic Hyperplasia

Keywords

BPH, prostatic hyperplasia, enlarged prostate, benign prostatic hypertrophy

Brief summary

The purpose of the study is to evaluate improvement in symptoms related to benign prostatic hyperplasia (BPH) in men treated with prostate artery embolization (PAE) using Embosphere Microspheres.

Detailed description

The study will evaluate improvement in symptoms associated with benign prostatic hyperplasia (BPH) in men with prostates larger than 90 grams treated with prostate artery embolization (PAE). Symptoms will be assessed utilizing the International Prostate Symptom Score (IPSS) to evaluate change from baseline at 12 months post PAE.

Interventions

DEVICEEmbosphere Microspheres

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

40 Years to 89 Years

Healthy volunteers

Inclusion criteria

* Patient has provided signed informed consent * Patient is aged greater than or equal to 40 and less than or equal to 89 years of age * Patient has a prostate size between 90g and 200g, as determined by MRI * Patient has experienced lower urinary tract symptoms (LUTS) for at least 6 months prior to study enrollment * Patient has an IPSS score of at least 13 at baseline * Patient is either: refractory to medical treatment, contraindicated to medical treatment, OR refuses medical treatment * Patient either: refuses surgical treatment OR is contraindicated for surgical treatment * Patient meets ONE of the following criteria: baseline PSA \< 4.0ng/mL (no prostate biopsy required) OR baseline PSA \>/= 4 ng/mL AND a negative prostate biopsy (minimum 12 core biopsy) within the prior 12 months

Exclusion criteria

* History of prostate, bladder, or rectal cancer * History of transurethral resection of the prostate (TURP), open prostate surgery, or radiofrequency or microwave therapies * History of open bladder, rectosigmoid colon, or other pelvic surgery * Patient is unwilling to discontinue alpha blockers 1 month after study treatment * Patient is unwilling to discontinue 5-alph reductase inhibitors 1 month after study treatment * Neurogenic bladder or other neurologic disorder impacting bladder function such as Parkinson's disease, multiple sclerosis, cerebral vascular accident or diabetes * Any other confounding bladder or urethral pathology, including urethral stricture, bladder neck contracture, or bladder atonia * Active prostatitis or urinary tract infection * Cystolithiasis within the past 3 months * Serum creatinine \> 1.7mg/dL * Inability to discontinue oral anticoagulant 2-5 days prior to study treatment * Coagulation disturbances not normalized by medical treatment * Iodinated contrast allergy that, in the opinion of the Investigator, cannot be adequately premedicated * Gelatin allergy * Known severe peripheral vascular disease or major iliac arterial occlusive disease * Interest in future fertility * Clinically significant cardiac arrhythmia or other cardiac disease (including congestive heart failure), uncontrolled diabetes mellitus, clinically significant respiratory disease, or known immunosuppression * Other condition that the Investigator believes puts the patient at risk for a complication during the procedure

Design outcomes

Primary

Measure	Time frame	Description
Improvement of Symptoms Associated With Benign Prostatic Hyperplasia (BPH) as Assessed by the International Prostate Symptom Score (IPSS)	12 months	The outcome measure was the International Prostate Symptom Score (IPSS). The IPSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). A higher score means a worse outcome.

Secondary

Measure	Time frame	Description
Change From Baseline in Serum Prostate Specific Antigen (PSA)	Baseline and12 Months	Serum prostate specific antigen (PSA) trends over time, may help to improve the specificity of PSA testing in men with BPH. A strong correlation has been demonstrated between prostate volume and serum PSA levels.
Change From Baseline in Prostate Size, as Determined by MRI	Baseline and 12 months	Prostate size was determined by measuring the prostate with magnetic resonance imaging (MRI) and calculating length x width x height x pi/6.
Change From Baseline in Peak Urine Flow Rate (Qmax) Determined by Urodynamic Testing	12 Months	Peak urine flow rate (Qmax) is the greatest volumetric flow rate of urine during urination, measured as the quantity of urine excreted in a specified period of time (per second or per minute). Qmax has become a primary objective parameter of treatment outcomes for various surgical and medical therapies for BPH. Unlike other prominent parameters of treatment outcome, Qmax responds minimally to placebo, making it an objective tool when evaluating a patient's response to therapy.
Change From Baseline in Post Void Residual Volume (PVR) as Determined by Urodynamic Testing	12 Months	Post void residual is a measurement of the amount of urine left in the bladder after voiding. It has traditionally been used to evaluate efficacy of treatment efforts. A positive response to treatment is associated with decreased PVR volumes.
Change From Baseline in Detrusor Muscle Pressure (Pdet) as Determined by Urodynamic Testing	12 Months	Detrusor muscle pressure (Pdet) is important when evaluating how strong the detrusor force must be to initiate urine flow in bladder outlet obstruction. Lower Pdet values are associated with a positive response to treatment.
Change From Baseline in Erectile Function as Determined by the International Index of Erectile Function (IIEF)	12 Months	The outcome measure was the International Index of Erectile Function (IIEF). The 15 question IIEF Questionnaire is a validated, multi-dimensional, self-administered investigation found to be useful in the clinical assessment of erectile dysfunction and treatment. It is examines the four main domains of male sexual function: erectile function, orgasmic function, sexual desire, and intercourse satisfaction. The answer to each question is given a score between 0 and 5 for a total score of 0-75 (higher score = less dysfunction). Higher scores mean better outcome.
Prostate Artery Embolization (PSA) Related Adverse Events	12 Months	Number of occurrences of adverse events with some relationship to the study procedure or study device. An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject and does not necessarily have to have a causal relationship with the treatment. In order to capture the most potentially relevant safety information during the study, AEs were assessed at each visit. AEs occurring during the clinical trial and the protocol-defined 12-month follow-up period were reported.
Overall Adverse Events	12 Months	All adverse events will be assessed for severity, relationship to study treatment, subsequent treatment required, and outcome

Other

Measure	Time frame	Description
Total PAE Procedure Time	Study treatment hospitalization (expected to be less than 1 day)	Parameter measured during the PAE (index procedure) for informational purposes. Total PAE procedure time was defined as time of femoral artery puncture to the time of time sheath removed from femoral artery.
Total Fluoroscopy Time for PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes.
Type of Contrast Media Delivered for PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes
Volume of Contrast Delivered for PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes
Volume of Embolic Delivered for PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes
Number of Origins of Prostatic Blood Supply	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes
Duration of [Urinary] Catheterization Post PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes
Duration of Hospitalization Post PAE	Study treatment hospitalization (expected to be less than 1 day)	Parameter to be measured during PAE procedure, for informational purposes

Countries

United States

Participant flow

Recruitment details

Following FDA and IRB approval for the study, recruitment began and the first subject was enrolled for the study on September 24, 2015. Enrollment was closed on June 29, 2017.

Pre-assignment details

The study involved a screening period during which patient eligibility was determined. There were no screen failures.

Participants by arm

Arm	Count
Treatment Arm Prostate artery embolization (PAE) with Embosphere Microspheres. Embosphere Microspheres	2
Total	2

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1

Baseline characteristics

Characteristic	Treatment Arm
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Age, Continuous	67.5 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Region of Enrollment United States	2 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	2 Participants
Use of 5 alpha reductase inhibitors	1 Participants
Use of alpha adrenergic blockers	2 Participants
Use of other BPH treatments	0 Participants
Use of other medications or supplements [to treat BPH]	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 2
other Total, other adverse events	1 / 2
serious Total, serious adverse events	1 / 2

Outcome results

Primary

Improvement of Symptoms Associated With Benign Prostatic Hyperplasia (BPH) as Assessed by the International Prostate Symptom Score (IPSS)

The outcome measure was the International Prostate Symptom Score (IPSS). The IPSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). A higher score means a worse outcome.

Time frame: 12 months

Population: Analysis population includes all subjects in the treatment arm who received unilateral or bilateral prostate artery embolization (PAE) and completed the study thru Visit 5 (12 month follow-up).

Arm	Measure	Value (NUMBER)
Treatment Arm	Improvement of Symptoms Associated With Benign Prostatic Hyperplasia (BPH) as Assessed by the International Prostate Symptom Score (IPSS)	7 units on a scale

Secondary

Change From Baseline in Detrusor Muscle Pressure (Pdet) as Determined by Urodynamic Testing

Detrusor muscle pressure (Pdet) is important when evaluating how strong the detrusor force must be to initiate urine flow in bladder outlet obstruction. Lower Pdet values are associated with a positive response to treatment.

Time frame: 12 Months

Population: The one subject who completed the study thru Visit 5 refused to undergo urodynamic testing at Visit 5. As a result the Pdet was not obtained. This was reported as a protocol deviation in the study.

Comparison: Statistical analysis was not performed as this data was not available for any subjects in the analysis population.

Secondary

Change From Baseline in Erectile Function as Determined by the International Index of Erectile Function (IIEF)

The outcome measure was the International Index of Erectile Function (IIEF). The 15 question IIEF Questionnaire is a validated, multi-dimensional, self-administered investigation found to be useful in the clinical assessment of erectile dysfunction and treatment. It is examines the four main domains of male sexual function: erectile function, orgasmic function, sexual desire, and intercourse satisfaction. The answer to each question is given a score between 0 and 5 for a total score of 0-75 (higher score = less dysfunction). Higher scores mean better outcome.

Time frame: 12 Months

Arm	Measure	Value (NUMBER)
Treatment Arm	Change From Baseline in Erectile Function as Determined by the International Index of Erectile Function (IIEF)	69 units on scale

Secondary

Change From Baseline in Peak Urine Flow Rate (Qmax) Determined by Urodynamic Testing

Peak urine flow rate (Qmax) is the greatest volumetric flow rate of urine during urination, measured as the quantity of urine excreted in a specified period of time (per second or per minute). Qmax has become a primary objective parameter of treatment outcomes for various surgical and medical therapies for BPH. Unlike other prominent parameters of treatment outcome, Qmax responds minimally to placebo, making it an objective tool when evaluating a patient's response to therapy.

Time frame: 12 Months

Population: The one subject who completed the study thru Visit 5 refused to undergo urodynamic testing at Visit 5. As a result the Qmax was not obtained. This was reported as a protocol deviation in the study.

Secondary

Change From Baseline in Post Void Residual Volume (PVR) as Determined by Urodynamic Testing

Post void residual is a measurement of the amount of urine left in the bladder after voiding. It has traditionally been used to evaluate efficacy of treatment efforts. A positive response to treatment is associated with decreased PVR volumes.

Time frame: 12 Months

Population: The one subject who completed the study thru Visit 5 refused to undergo urodynamic testing at Visit 5. As a result the PVR was not obtained. This was reported as a protocol deviation in the study.

Comparison: Statistical analysis was not performed as this data was not available for any subjects in the analysis population.

Secondary

Change From Baseline in Prostate Size, as Determined by MRI

Prostate size was determined by measuring the prostate with magnetic resonance imaging (MRI) and calculating length x width x height x pi/6.

Time frame: Baseline and 12 months

Arm	Measure	Value (NUMBER)
Treatment Arm	Change From Baseline in Prostate Size, as Determined by MRI	111 grams

Secondary

Change From Baseline in Serum Prostate Specific Antigen (PSA)

Serum prostate specific antigen (PSA) trends over time, may help to improve the specificity of PSA testing in men with BPH. A strong correlation has been demonstrated between prostate volume and serum PSA levels.

Time frame: Baseline and12 Months

Arm	Measure	Value (NUMBER)
Treatment Arm	Change From Baseline in Serum Prostate Specific Antigen (PSA)	2.26 ng/mL

Secondary

Overall Adverse Events

All adverse events will be assessed for severity, relationship to study treatment, subsequent treatment required, and outcome

Time frame: 12 Months

Population: Analysis population includes all subjects, in the treatment arm, for whom prostate artery embolization (PAE) was attempted regardless of whether the subject received a unilateral PAE, bilateral PAE, or the attempted PAE was aborted.

Arm	Measure	Group	Value (NUMBER)
Treatment Arm	Overall Adverse Events	Catheter site burning	1 occurrence
Treatment Arm	Overall Adverse Events	Pelvic pain	1 occurrence
Treatment Arm	Overall Adverse Events	Dysuria	1 occurrence
Treatment Arm	Overall Adverse Events	Pollakiuria	1 occurrence
Treatment Arm	Overall Adverse Events	Bladder irritation	1 occurrence
Treatment Arm	Overall Adverse Events	Nasopharyngitis	1 occurrence
Treatment Arm	Overall Adverse Events	Urinary tract infection	2 occurrence
Treatment Arm	Overall Adverse Events	Acute myocardial infarction	1 occurrence
Treatment Arm	Overall Adverse Events	Acute sinusitis	1 occurrence
Treatment Arm	Overall Adverse Events	Allergic rhinitis	1 occurrence

Secondary

Prostate Artery Embolization (PSA) Related Adverse Events

Number of occurrences of adverse events with some relationship to the study procedure or study device. An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject and does not necessarily have to have a causal relationship with the treatment. In order to capture the most potentially relevant safety information during the study, AEs were assessed at each visit. AEs occurring during the clinical trial and the protocol-defined 12-month follow-up period were reported.

Time frame: 12 Months

Arm	Measure	Category	Value (COUNT_OF_UNITS)
Treatment Arm	Prostate Artery Embolization (PSA) Related Adverse Events	Catheter site burning	1 occurrence
Treatment Arm	Prostate Artery Embolization (PSA) Related Adverse Events	Pelvic pain	1 occurrence
Treatment Arm	Prostate Artery Embolization (PSA) Related Adverse Events	Dysuria	1 occurrence
Treatment Arm	Prostate Artery Embolization (PSA) Related Adverse Events	Pollakiuria	1 occurrence
Treatment Arm	Prostate Artery Embolization (PSA) Related Adverse Events	Bladder irritation	1 occurrence

Other Pre-specified