Clinical trial NCT02869971: Prostatic Artery Embolization Versus Medical Treatment in Symptomatic Benign Prostatic Hyperplasia
Official title: Prostatic Artery Embolization Versus Medical Treatment in Symptomatic Benign Prostatic Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Benign Prostatic Hyperplasia
Keywords: Prostatic artery embolization
Combined Therapy
IPSS
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2016-08-17
Enrollment: 90
Sex: MALE
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to compare the 9-month effect on lower urinary tract symptoms (LUTS) of Prostatic Artery Embolization (PAE) using Embosphere® versus Standard Combined Therapy (alpha-blockers plus 5 alpha-reductase inhibitors) in patients with symptomatic BPH who failed after a first line medical treatment with alpha-blockers.

The secondary objectives of this study are to:

* Estimate the impact of the 2 strategies on benign prostatic hyperplasia specific Health Status (i.e. urinary and sexual signs and symptoms) at 3, 9, 18, and 24 months, as well as the side effects of the 2 strategies;
* Report the safety of PAE;
* Evaluate patient's adherence to medical treatment;
* Analyse the costs of each strategy and report the incremental efficiency (incremental cost utility ratio) of prostatic artery embolization compared to medical treatment.

Detailed description: Benign Prostatic Hyperplasia (BPH) is the primary cause of lower urinary tract symptoms (LUTS) and affects \> 50% of men \>60 years. Moderate to severe symptoms prevalence is around 14% in France, and the proportion of men with moderate to severe symptoms doubles with each decade of age. The first-line treatment of bothersome BPH-related LUTS is medical therapy as recommended by French and European guidelines. 5α reductase inhibitors (5-ARI) can be combined with alpha-blockers and allow reduction of the size of the prostate and LUTS improvement. The severity of symptoms is usually assessed using the International prostate symptom score (IPSS) which is the standard questionnaire for the objective assessment of LUTS.

Recently, Prostatic Artery Embolization (PAE) has been proposed to treat symptomatic BPH with good safety and efficacy in single-centre studies (12-point IPSS reduction at 3 months maintained up to one year. In a randomized trial comparing PAE versus transurethral resection of prostate (TURP), Gao reported a 16-point IPSS reduction at 6 months, and an increase in the maximum urinary flow rate (Qmax) comprised between 12 ml/s and 24 ml/s at 6 months and up to 21 ml/s at 2 years. The complication rate is low (a few cases of bladder ulcer have been published) and the patient generally experiences mild post-embolization symptoms for few days.

PAE can be performed during a one-day hospitalisation and could be very attractive to patients which have insufficient benefit of medical treatment or who have side effects affecting their quality of life. The most used device for PAE is Embosphere® (Merit Medical). It bears the European CE (Conforme aux Exigences) marking for this specific indication and approximately 500 patients have been treated with it worldwide. Nonetheless, no big randomized study has proven its efficacy compared with best medical treatment. A study comparing PAE using Embosphere® and surgery (TURP) is currently enrolling patients; no patients could be included in France because men with BPH refused to be potentially assigned the surgical arm.

To properly evaluate PAE, the investigators designed the PARTEM trial, which has received the support of both the Societe Francaise de Radiologie (French society of radiology) and of the Association Francaise d'Urologie (French association of urology).

PARTEM will compare prospectively the benefit of PAE using Embosphere® to the benefit of combined medical treatment (Combodart®: Dutasteride 0.5mg Tamsulosin 0.4mg) at 9 months with an extended follow up at 24 months in order to evaluate the stability of results in both groups.

The investigators plan a multicentre, prospective, randomized, open label, parallel trial, comparing PAE to Combined Therapy (CT: alpha-blockers + 5-ARI treatment). Treatments will be allocated by minimization with a 1:1 ratio, based on study centre, IPSS score (moderate/severe) and prostate volume (\< 80 g/≥80 g).

This study is designed to demonstrate the superiority of PAE to decrease LUTS compared to best medical treatment.

Eligibility criteria: Inclusion Criteria:

* Men aged\>= 50 and \<=85 years AND
* Moderate to severe LUTS defined as IPSS \> 11, and QoL \> 3 AND
* No improvement after an alpha blocker treatment line (Tamsulosin 0.4 mg p.d. during 1 month) AND
* Prostatic volume \>=50 ml AND
* Affiliated to a French health insurance system

Exclusion Criteria:

* Severe allergy to iodine contrast agent
* Treatment with 5-ARI on the last 6 months
* Suspected prostate cancer requiring specific management
* On-going prostatitis
* On-going urinary retention
* On-going acute urinary infection
* Acontractile detrusor
* Neurogenic lower urinary tract dysfunction
* Urethral stenosis
* Bladder diverticulum
* Bladder stone with surgical indication
* Patient refusing PAE
* Creatinine clearance \<40 ml/min
* Severe liver failure
* Contra-indication to alpha-blockers
* Hypersensitivity to dutasteride, other 5-alpha reductase inhibitors, tamsulosin (including case of tamsulosin induced angioedema), soya, peanut or one of the excipients
* Hypersensitivity to gelatin or collagen
* Patients ineligible for pelvic angiography
* History of orthostatic hypotension
* Patient unable or unwilling to provide written informed consent
* Patient under legal protection

Primary outcomes:
measure: Change in IPSS score
timeFrame: 9 months
Secondary outcomes:
measure: Number of Adverse Events
timeFrame: 3, 9, 18, 24 months
measure: IPSS
timeFrame: 3, 18, 24 months
measure: Qmax
timeFrame: 3, 9, 24 months
measure: International Index of Erectile Function (IIEF) score
timeFrame: 3, 9, 18, 24 months
measure: prostate volume
timeFrame: 3, 9, 24 months
measure: Prostate-Specific Antigen (PSA) level
timeFrame: 3, 9, 18, 24 months
measure: Quality of life score
timeFrame: 3, 9, 18, 24 months
measure: Treatment units' account
timeFrame: 3, 9 months
measure: Adherence to treatment questionnaire
timeFrame: 3, 9 months
measure: number of PAE
timeFrame: 24 months
measure: number of surgical treatment
timeFrame: 24 months
measure: number of medication
timeFrame: 3, 9, 18, 24 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: CHU de Lyon hopital Edouard Herriot
state: Auvergne-Rhone-Alpes
city: Pierre-Benite
country: France
facility: CHU de Lyon centre hospitalier Lyon Sud
state: Auvergne-Rhone-Alpes
city: Rennes
country: France
facility: CHU Rennes hopital Pontchaillou
state: Bretagne
city: Montpellier
country: France
facility: CHU Montpellier hopital Arnaud de Villeneuve
state: Languedoc-Roussillon-Midi-Pyrenees
city: Montpellier
country: France
facility: CHU Montpellier hopital Lapeyronie
state: Languedoc-Roussillon-Midi-Pyrenees
city: Bordeaux
country: France
facility: CHU de Bordeaux groupe hospitalier Pellegrin
state: Nouvelle-Aquitaine
city: Limoges
country: France
facility: CHU de Limoges
state: Nouvelle-Aquitaine
city: Marseille
country: France
facility: AP-HM hopital la Conception
state: Provence-Alpes-Cote d'Azur
city: Marseille
country: France
facility: AP-HM hopital de la Timone
state: Provence-Alpes-Cote d'Azur
city: Creteil
country: France
facility: AP-HP hopital Henri-Mondor
state: Île-de-France
city: Paris
country: France
facility: AP-HP - Hôpital Saint-Louis
state: Île-de-France
city: Paris
country: France
facility: AP-HP hopital Cochin
state: Île-de-France
city: Paris
country: France
facility: AP-HP Hopital Europeen Georges Pompidou
state: Île-de-France
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marc Sapoval, MD
role: PRINCIPAL_INVESTIGATOR
References: