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Trial registered on ANZCTR


Registration number
ACTRN12617001199303
Ethics application status
Approved
Date submitted
10/08/2017
Date registered
16/08/2017
Date last updated
17/12/2018
Date data sharing statement initially provided
17/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Medical Therapy versus Prostate Artery Embolisation in treatment naïve men with symptomatic benign prostate hyperplasia (MEDS vs PAE)
Scientific title
Medical Therapy versus Prostate Artery Embolisation in treatment naïve men with symptomatic benign prostate hyperplasia (MEDS vs PAE)
Secondary ID [1] 292629 0
None
Universal Trial Number (UTN)
U1111-1200-5385
Trial acronym
MEDS vs PAE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Benign prostate hyperplasia 304349 0
Condition category
Condition code
Renal and Urogenital 303683 303683 0 0
Other renal and urogenital disorders
Surgery 303684 303684 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two treatment groups in this trial; prostate artery embolization (new intervention) and medical therapy (Duodart, current standard treatment).

Prostate artery embolisation procedures are performed by interventional radiologists experienced in prostate artery embolisation. The procedure takes approximately 120 minutes. Procedures will be performed with a right femoral or left brachial artery approach, using 4- or 5- French sheaths. 5-Fr 125 cm Impulse (Merit Medical, Utah, USA) and 4-Fr 120 cm Cobra Glidecath (Terumo, New Jersey, USA) catheters are combined with 150 cm standard Glidewires (Terumo, New Jersey, USA) to access the internal iliac arteries. Microcatheters 2.0Fr Progreat (Terumo, New Jersey, USA) or 1.7Fr SL-10 (Stryker, Michigan, USA) are used to selectively catheterise the prostate arteries over microwires, either 0.016” Radifocus Guidewire GT (Terumo, New Jersey, USA) or 0.014” Synchro Standard (Stryker, Michigan, USA). Following selective catheterisation of the prostate arteries and positioning of the microcatheter tip within the distal prostate artery, an on-table Dyna CT scan using hand-injected 1-2 ml contrast (Ultravist 300, Bayer, Leverkusen, Germany) in a 3 ml Medallion syringe (Merit Medical, Utah, USA) is performed and reviewed in three planes to assess for non-prostatic enhancement. Once the operators are confident that no off-target enhancement is evident, a single unit syringe of 250 micron Embozene (Celenova Biosciences, Texas, USA) is prepared by diluting the Embozene particles with full contrast to 1/16 (6.25%) of the original concentration. Embolisation is then performed by slowly injecting the diluted particles until complete stasis of the prostate artery has been achieved.

Medical therapy with Duodart, a fixed-dose combination of 0.5 mg Dutasteride (a 5-alpha reductase inhibitor) and 0.4 mg Tamsulosin (a-blocker) will be taken as a once daily oral tablet.

Patients in each group will be followed-up at six months post-treatment commencement and any patient who has not satisfactorily responsed to their treatment will be offered the other treatment option. Response to treatment will be assessed based on a range of parameters, these include; severity of symptoms (IPSS questionnaire with quality of life question); change in prostate volume (measured by ultrasound); change in bladder function (ultrasound and urodynamic testing); treatment side effects (questionnaire designed specifically for this study); and the patient's satisfaction with their response to treatment (questionnaire designed specifically for this study). Patient eligibility for cross over will be assessed on a case-by-case basis and permitted if; a) the patient is unsatisfied with their response to treatment and b) if the treating specialists (urologist and interventional radiologist) agree an improved response is likely with treatment crossover.
Intervention code [1] 298857 0
Treatment: Other
Intervention code [2] 298858 0
Treatment: Surgery
Comparator / control treatment
Medical therapy with Duodart, a fixed-dose combination of 0.5 mg Dutasteride (a 5-alpha reductase inhibitor) and 0.4 mg Tamsulosin (a-blocker). Duodart will be taken as one oral tablet once daily for the duration of this project (24 months, unless crossed over at 6 months). Adherence will be monitored during follow-up appointments and reasons for non-compliance, for example negative side effects, recorded.
Control group
Active

Outcomes
Primary outcome [1] 303050 0
To assess the efficacy of combined medical therapy (Duodart) versus PAE as frontline treatment for BPH in treatment-naïve patients, as assessed by: Absolute and % change in IPSS.
Timepoint [1] 303050 0
6-months (primary timepoint) and 24-months post-treatment initiation
Primary outcome [2] 303052 0
To assess the efficacy of combined medical therapy (Duodart) versus PAE as frontline treatment for BPH in treatment-naïve patients, as assessed by: Absolute and % change in QoL scores as assessed within the IPSS questionnaire.
Timepoint [2] 303052 0
6-months (primary timepoint) and 24-months post-treatment initiation
Secondary outcome [1] 337777 0
To further evaluate and compare medication and PAE treatment options by assessing: Change in urinary Qmax (peak flow rate, measured on ultrasound)
Timepoint [1] 337777 0
6-months and 24-months post-treatment initiation
Secondary outcome [2] 337778 0
To further evaluate and compare medication and PAE treatment options by assessing: Change in post-void residual volume (PVR, measured on ultrasound)
Timepoint [2] 337778 0
6-months and 24-months post-treatment initiation
Secondary outcome [3] 337779 0
To further evaluate and compare medication and PAE treatment options by assessing: Change in prostate volume (absolute and % reduction). Prostate volumes will be calculated from CT, MRI and ultrasound scan measurements
Timepoint [3] 337779 0
6-months and 24-months post-treatment initiation
Secondary outcome [4] 337780 0
To further evaluate and compare medication and PAE treatment options by assessing: Side effect/adverse outcome profile of medication v PAE (type of side-effects, severity and duration) . Side effect profiles will be assessed via a questionnaire designed for this study
Timepoint [4] 337780 0
6-months and 24-months post-treatment initiation
Secondary outcome [5] 337781 0
To further evaluate and compare medication and PAE treatment options by assessing: PSA levels via serum blood tests
Timepoint [5] 337781 0
6-months and 24-months post-treatment initiation
Secondary outcome [6] 337782 0
To further evaluate and compare medication and PAE treatment options by assessing: Changes in urodynamic study results pre and post treatment. The key urodynamic study test will be uroflowmetry (flow rate of urine) performed by a urologist.
Timepoint [6] 337782 0
6-months and 24-months post-treatment initiation
Secondary outcome [7] 337784 0
To further evaluate and compare medication and PAE treatment options by assessing: Overall satisfaction with treatment as assessed via a questionnaire specifically designed for use in this study
Timepoint [7] 337784 0
6-months and 24-months post-treatment initiation

Eligibility
Key inclusion criteria
BPH with prostate volume > 50cc
Moderate-severe lower urinary tract symptoms (IPSS >8)
Peak urinary flow <12ml/sec
Obstructive urodynamics
Treatment-naive, i.e. no previous medical therapy for BPH.
Minimum age
50 Years
Maximum age
80 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Prostate malignancy
Neurogenic bladder
Renal failure eGFR <35ml/min
Severe peripheral vascular disease
Urethral or bladder pathology
History of medical therapy for BPH.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patients will be randomised to receive either combination medical therapy (Duodart) or to undergo a PAE procedure. Any patient who is not satisfied with their response to treatment by 6 months will be assessed and offered the alternative treatment option if the treating specialists (urologist and interventional radiologist) are in agreement that crossover has the potential to improve patient response.
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 8757 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 16877 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 297260 0
Commercial sector/Industry
Name [1] 297260 0
UnitingCare Medical Imaging
Address [1] 297260 0
The Wesley Hospital
30 Chasely Street
Auchenflower, QLD, 4066
Country [1] 297260 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
UnitingCare Medical Imaging
Address
The Wesley Hospital
30 Chasely Street
Auchenflower, QLD, 4066
Country
Australia
Secondary sponsor category [1] 296233 0
None
Name [1] 296233 0
Address [1] 296233 0
Country [1] 296233 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298377 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [1] 298377 0
UnitingCare Health Human Research Ethics Committee
The Wesley Hospital
PO Box 499
Auchenflower, QLD, 4066
Ethics committee country [1] 298377 0
Australia
Date submitted for ethics approval [1] 298377 0
20/06/2017
Approval date [1] 298377 0
19/09/2017
Ethics approval number [1] 298377 0
1735

Summary
Brief summary
Prostate artery embolisation (PAE) is a minimally invasive technique that has proven effective in decreasing lower urinary tract symptoms (LUTS) in men with medically refractive benign prostatic hyperplasia (BPH). BPH, or an enlarging prostate, affects more than 50% of males older than 60 years. LUTS include multiple night-time urination, urgency, hesitancy initiating urination, weak or interrupted urinary stream and post-urination dribble.

The primary goals of BPH therapy are to decrease LUTS, improve quality of life (QoL) and prevent disease progression. For men with mild-to-moderate symptoms, sequential step-up therapy starting with watchful waiting and escalating to single or multiple medical therapies and, in some cases surgery, constitutes common clinical practice.

A common combined medical therapy is Duodart, a fixed-dose combination of 0.5 mg Dutasteride and 0.4 mg Tamsulosin, that is usually prescribed for men with more severe prostate enlargement. The benefits of combined therapy can be explained by the synergistic mechanisms of action of the component drugs. Tamsulosin, an a-blocker, relaxes the smooth muscle tissue in the prostate and bladder neck, allowing urine to flow more freely. Treatment with Tamsulosin provides improvement of LUTS but has no effect on prostate growth. Dutasteride, a 5-alpha reductase inhibitor, blocks the production of dihydrotestosterone, the metabolic driver of prostate growth. Thus Dutasteride treatment reduces prostate size and impedes disease progression related to prostatic overgrowth. Adverse side effects associated with these medication include retrograde ejaculation, urinary incontinence and impotence. Overall, medications are generally ineffective for long-term control of LUTS, and medical therapies are often abandoned because of poor tolerance and inefficacy.

PAE is emerging as a viable alternative to medication and invasive surgery for patients with LUTS. PAE has already shown promise as a short to medium-term treatment in patients who are not willing, or not able to undergo surgery. Medium-term follow-up in patients who have undergone PAE demonstrates that:
• Improved symptoms and increased quality of life persist for at least 5 years in a majority of patients,
• PAE is more efficacious than medical therapy alone,
• PAE causes fewer side-effects than surgical resection,
• PAE can be repeated if required, and does not preclude future surgical options.

To date, a direct comparison between PAE and medical therapy in a randomised controlled trial has not been performed. The study proposed here will extend knowledge in this area by investigating whether PAE is a suitable intervention in treatment-naive men who would otherwise be prescribed medications as a first-line treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76882 0
Dr Nicholas Brown
Address 76882 0
Wesley Medical Imaging
30 Chasely Street
Auchenflower, QLD, 4066
Country 76882 0
Australia
Phone 76882 0
+61403 324 362
Fax 76882 0
Email 76882 0
nibrown@tpg.com.au
Contact person for public queries
Name 76883 0
Dr Rhiannon McBean
Address 76883 0
UnitingCare Medical Imaging 30 Chasely Street Auchenflower, QLD, 4066
Country 76883 0
Australia
Phone 76883 0
+61 7 33775938
Fax 76883 0
Email 76883 0
rmcbean@ucmi.com.au
Contact person for scientific queries
Name 76884 0
Dr Rhiannon McBean
Address 76884 0
UnitingCare Medical Imaging 30 Chasely Street Auchenflower, QLD, 4066
Country 76884 0
Australia
Phone 76884 0
+61 7 33775938
Fax 76884 0
Email 76884 0
rmcbean@ucmi.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Given the small number of participants (40 maximum in two treatment groups), data collected in this study is unlikely to be of value to meta-analysis by external investigators. However, the Principal Investigator would be happy to consider requests for IPD at a later date.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
Not applicable