Prostatic Artery Embolization vs. Pharmacotherapy for LUTS/BPH

Study Overview
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Brief Summary
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This study compares safety and efficacy of prostatic artery embolization and pharmacotherapy in the treatment of lower urinary tract symptoms associated wit benign prostatic hyperplasia.

Official Title
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Prostatic Artery Embolization vs. Pharmacotherapy for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: a Multicenter Randomized Controlled Trial

Conditions
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Benign Prostatic Hyperplasia, Pharmacotherapy, Prostatic Artery Embolization, Minimally Invasive Treatment

Intervention / Treatment
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* Procedure: Prostatic Artery Embolization (PAE)
* Drug: Pharmacotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men ≥45 years of age lower urinary tract symptoms assigned to BPH (diagnosis by medical history and physical examination) IPSS ≥ 8 points QoL ≥ 3 points Qmax ≤ 15 ml/s with a minimum voided volume ≥ 125 ml informed consent for study participation Exclusion Criteria: renal impairment (GFR < 30ml/min) previous prostatic surgery 5-alpha reductase inhibitor (5-ARI) use within 6 mo (or dutasteride within 12 mo) prior to entry, or use of an α-blocker or phytotherapy for BPH within 2 weeks prior to entry history or evidence of prostate cancer absolute indication for surgical treatment of complications related to BPH (i.e. bladder stones, renal impairment due to bladder outlet obstruction) history of neurogenic bladder dysfunction not able to complete questionnaires due to cognitive or thought disorders language skills insufficient for informed consent and / or completion of questionnaires

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 100 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomized controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prostatic Artery Embolization (PAE)<br>PAE will be performed as an inpatient or outpatient procedure by interventional radiologists who are familiar with the procedure and according to established techniques. A unilateral femoral sheath is placed in the right common femoral artery under local anaesthesia. The prostatic arterial supply is identified by selective internal iliac arteriography. Prostatic arteries are selectively catheterised and embolised by use of 250-600 μm microspheres . PAE is performed bilaterally if possible and considered successful in the absence of the normal blush of the prostate and stasis of flow in the prostate arteries on angiography after embolisation. | Procedure: Prostatic Artery Embolization (PAE)<br>* Prostatic artery embolization will be performed under local anesthesia according to well established and standardized techniques.<br>|
| Placebo Comparator: Pharmocotherapy<br>Pharmacotherapy will be performed using α1-blockers and 5α-reductase inhibitors in accordance with the EAU recommendations. Thus, patients with a prostate size smaller than 40mL will be treated with 0.4 mg tamsulosin once daily, while patients with larger prostates will be treated with 0.4 mg tamsulosin plus 0.5 mg dutasteride once daily during the complete study follow-up. | Drug: Pharmacotherapy<br>* Pharmacotherapy will be performed using α1-blockers and 5α-reductase inhibitors in accordance with the EAU recommendations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Prostate Symptoms Score (IPSS) | The International Prostate Symptoms Score (IPSS) measures the degree of symptoms associated with benign prostatic hyperplasia (BPH). Range of values 0-35 points. Higher values indicate more severe symptoms. | 24 months after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Prostate Symptoms Score (IPSS) | The International Prostate Symptoms Score (IPSS) measures the degree of symptoms associated with benign prostatic hyperplasia (BPH). Range of values 0-35 points. Higher values indicate more severe symptoms. | 6 weeks after treatment initiation | 
| International Prostate Symptoms Score (IPSS) | The International Prostate Symptoms Score (IPSS) measures the degree of symptoms associated with benign prostatic hyperplasia (BPH). Range of values 0-35 points. Higher values indicate more severe symptoms. | 6 months after treatment initiation | 
| International Prostate Symptoms Score (IPSS) | The International Prostate Symptoms Score (IPSS) measures the degree of symptoms associated with benign prostatic hyperplasia (BPH). Range of values 0-35 points. Higher values indicate more severe symptoms. | 1 year after treatment initiation | 
| International Prostate Symptoms Score (IPSS) | The International Prostate Symptoms Score (IPSS) measures the degree of symptoms associated with benign prostatic hyperplasia (BPH). Range of values 0-35 points. Higher values indicate more severe symptoms. | 5 year after treatment initiation | 
| Self-assessed goal achievement (SAGA) | SAGA is a PROM focusing on individual treatment goals SAGA is a patient reported outcome measure focusing on individual treatment goals | 6 weeks after treatment initiation | 
| Self-assessed goal achievement (SAGA) | SAGA is a PROM focusing on individual treatment goals SAGA is a patient reported outcome measure focusing on individual treatment SAGA is a PROM focusing on individual treatment goals | 6 months after treatment initiation | 
| Self-assessed goal achievement (SAGA) | SAGA is a PROM focusing on individual treatment goals SAGA is a patient reported outcome measure focusing on individual treatment goals | 1 year after treatment initiation | 
| Self-assessed goal achievement (SAGA) | SAGA is a PROM focusing on individual treatment goals SAGA is a patient reported outcome measure focusing on individual treatment goals | 2 years after treatment initiation | 
| Self-assessed goal achievement (SAGA) | SAGA is a PROM focusing on individual treatment goals SAGA is a patient reported outcome measure focusing on individual treatment goals | 5 years after treatment initiation | 
| Maximum urinary stream (Qmax) | Urinary stream will be measured by free uroflowmetry and recorded in mL per second. Higher values indicate a better maximum urinary stream. | 6 weeks after treatment initiation | 
| Maximum urinary stream (Qmax) | Urinary stream will be measured by free uroflowmetry and recorded in mL per second. Higher values indicate a better maximum urinary stream. | 6 months after treatment initiation | 
| Maximum urinary stream (Qmax) | Urinary stream will be measured by free uroflowmetry and recorded in mL per second. Higher values indicate a better maximum urinary stream. | 1 year after treatment initiation | 
| Maximum urinary stream (Qmax) | Urinary stream will be measured by free uroflowmetry and recorded in mL per second. Higher values indicate a better maximum urinary stream. | 2 years after treatment initiation | 
| Maximum urinary stream (Qmax) | Urinary stream will be measured by free uroflowmetry and recorded in mL per second. Higher values indicate a better maximum urinary stream. | 5 years after treatment initiation | 
| Post void residual urine (PVR) | Post void residual is measured after voiding by transabdominal ultrasound and calculated in mL. Higher values indicate more post void residual urine and a worse ability to empty the bladder. | 6 weeks after treatment initiation | 
| Post void residual urine (PVR) | Post void residual is measured after voiding by transabdominal ultrasound and calculated in mL. Higher values indicate more post void residual urine and a worse ability to empty the bladder. | 6 months after treatment initiation | 
| Post void residual urine (PVR) | Post void residual is measured after voiding by transabdominal ultrasound and calculated in mL. Higher values indicate more post void residual urine and a worse ability to empty the bladder. | 1 year after treatment initiation | 
| Post void residual urine (PVR) | Post void residual is measured after voiding by transabdominal ultrasound and calculated in mL. Higher values indicate more post void residual urine and a worse ability to empty the bladder. | 2 years after treatment initiation | 
| Post void residual urine (PVR) | Post void residual is measured after voiding by transabdominal ultrasound and calculated in mL. Higher values indicate more post void residual urine and a worse ability to empty the bladder. | 5 years after treatment initiation | 
| Prostate volume | Prostate volume measured by transrectal ultrasound. This examination is only performed at selected food-up visits (i.e. 6mo, 2y, 5y) | 6 moths after treatment initiation | 
| Prostate volume | Prostate volume measured by transrectal ultrasound. This examination is only performed at selected food-up visits (i.e. 6mo, 2y, 5y) | 2 years after treatment initiation | 
| Prostate volume | Prostate volume measured by transrectal ultrasound. This examination is only performed at selected food-up visits (i.e. 6mo, 2y, 5y) | 5 years after treatment initiation | 
| Prostate specific antigen (PSA) | laboratory test | 6 months after treatment initiation | 
| Prostate specific antigen (PSA) | laboratory test | 1 year after treatment initiation | 
| Prostate specific antigen (PSA) | laboratory test | 2 years after treatment initiation | 
| Prostate specific antigen (PSA) | laboratory test | 5 years after treatment initiation | 
| Safety / adverse events | Number of patients developing adverse events: Classification will be performed according to Clavien-Dindo classification and CTCAE. | 6 weeks after treatment initiation | 
| Safety / adverse events | Number of patients developing adverse events: Classification will be performed according to Clavien-Dindo classification and CTCAE. | 6 months after treatment initiation | 
| Safety / adverse events | Number of patients developing adverse events: Classification will be performed according to Clavien-Dindo classification and CTCAE. | 1 year after treatment initiation | 
| Safety / adverse events | Number of patients developing adverse events: Classification will be performed according to Clavien-Dindo classification and CTCAE. | 2 year after treatment initiation | 
| Safety / adverse events | Number of patients developing adverse events: Classification will be performed according to Clavien-Dindo classification and CTCAE. | 5 year after treatment initiation | 
| Erectile function | Assessed by the questionnaire IIEF-5. Score of IIEF-5 can range from 0 to 25 points. Higher values indicate a better erectile function. | 6 weeks after treatment initiation | 
| Erectile function | Assessed by the questionnaire IIEF-5. Score of IIEF-5 can range from 0 to 25 points. Higher values indicate a better erectile function. | 6 months after treatment initiation | 
| Erectile function | Assessed by the questionnaire IIEF-5. Score of IIEF-5 can range from 0 to 25 points. Higher values indicate a better erectile function. | 1 year after treatment initiation | 
| Erectile function | Assessed by the questionnaire IIEF-5. Score of IIEF-5 can range from 0 to 25 points. Higher values indicate a better erectile function. | 2 year after treatment initiation | 
| Erectile function | Assessed by the questionnaire IIEF-5. Score of IIEF-5 can range from 0 to 25 points. Higher values indicate a better erectile function. | 5 year after treatment initiation | 
| Ejaculatory function | Assessed by the questionnaire Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD). Ejaculatory function total score (questions 1-3, possible range 0-15, higher values indicate better ejaculatory function, and MSHQ-EjD ejaculatory bother item (question 4, possible range 0-5, higher values indicate more bother). | 6 weeks after treatment initiation | 
| Ejaculatory function | Assessed by the questionnaire Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD). Ejaculatory function total score (questions 1-3, possible range 0-15, higher values indicate better ejaculatory function, and MSHQ-EjD ejaculatory bother item (question 4, possible range 0-5, higher values indicate more bother). | 6 months after treatment initiation | 
| Ejaculatory function | Assessed by the questionnaire Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD). Ejaculatory function total score (questions 1-3, possible range 0-15, higher values indicate better ejaculatory function, and MSHQ-EjD ejaculatory bother item (question 4, possible range 0-5, higher values indicate more bother). | 1 year after treatment initiation | 
| Ejaculatory function | Assessed by the questionnaire Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD). Ejaculatory function total score (questions 1-3, possible range 0-15, higher values indicate better ejaculatory function, and MSHQ-EjD ejaculatory bother item (question 4, possible range 0-5, higher values indicate more bother). | 2 years after treatment initiation | 
| Ejaculatory function | Assessed by the questionnaire Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD). Ejaculatory function total score (questions 1-3, possible range 0-15, higher values indicate better ejaculatory function, and MSHQ-EjD ejaculatory bother item (question 4, possible range 0-5, higher values indicate more bother). | 5 years after treatment initiation | 
| Need for additional drug treatment, surgical treatment or change of medical treatment assessed | assessed by patient interviews at follow up visit | 6 weeks after treatment initiation | 
| Need for additional drug treatment, surgical treatment or change of medical treatment assessed | assessed by patient interviews at follow up visit | 6 moths after treatment initiation | 
| Need for additional drug treatment, surgical treatment or change of medical treatment assessed | assessed by patient interviews at follow up visit | 1 year after treatment initiation | 
| Need for additional drug treatment, surgical treatment or change of medical treatment assessed | assessed by patient interviews at follow up visit | 2 years after treatment initiation | 
| Need for additional drug treatment, surgical treatment or change of medical treatment assessed | assessed by patient interviews at follow up visit | 5 years after treatment initiation | 
| Analysis of cost-effectiveness using quality-adjusted life years (QALY) | One QALY equates to one year in perfect health. QALY scores range from 1 (perfect health) to 0 (dead). To estimate QALY costs will be calculated by calculation of treatment costs, and quality of life will be assessed using the questionnaire EQ-5D. EQ-5D measures five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents self-rate their level of severity for each dimension using a five-level scale. The questionnaire can define 3,125 different health states. | 2 years after treatment initiation | 
| Analysis of cost-effectiveness using quality-adjusted life years (QALY) | One QALY equates to one year in perfect health. QALY scores range from 1 (perfect health) to 0 (dead). To estimate QALY costs will be calculated by calculation of treatment costs, and quality of life will be assessed using the questionnaire EQ-5D. EQ-5D measures five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents self-rate their level of severity for each dimension using a five-level scale. The questionnaire can define 3,125 different health states. | 5 years after treatment initiation |