Clinical trial NCT05686525: Clinical Trial on the Effectiveness of TUMT Compared to PAE in Reducing Severe LUTS in Men with BPH
Official title: Non-inferiority, Randomised, Open-label Clinical Trial on the Effectiveness of Transurethral Microwave Thermotherapy Compared to Prostatic Artery Embolisation in Reducing Severe Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostatic Hyperplasia
Lower Urinary Tract Symptoms
Keywords: Embolization, Therapeutic
Prostatic Artery Embolization
Transurethral Microwave Thermotherapy
Patient Reported Outcome Measures
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Herlev and Gentofte Hospital
First posted: 2023-01-17
Enrollment: 220
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will randomize approximately 220 patients with an anticipated 10% dropout (N = 200). The study will assign patients in a 1:1 manner to either Arm 1: TUMT or Arm 2: PAE.
Primary purpose: TREATMENT

Brief summary: The TUMT-PAE-1 trial is a randomised clinical trial aiming to compare the effectiveness of transurethral microwave thermotherapy (TUMT) with prostatic artery embolisation (PAE) in reducing urinary symptoms caused by prostate gland enlargement. The assessment will be done by patient reported and functional outcome measures. The primary purpose is to evaluate the urinary symptoms six months after the procedure, measured by the International Prostate Symptom Score (IPSS).

Detailed description: One fourth of men older than 70 years have moderate to severe lower urinary tract symptoms (LUTS) that impair their quality of life (QOL). This is most frequently caused by benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) is still regarded as the gold standard for surgical treatment of BPH. However, TURP is only an option for patients fit for general anesthesia and can result in complications. Consequently, several less invasive procedures have been developed, as prostatic artery embolization (PAE) and transurethral microwave thermotherapy (TUMT).

The objective of this clinical trial is to assess if transurethral microwave thermotherapy (TUMT) is non-inferior to prostatic artery embolization (PAE) in reducing lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). The primary aim is to compare LUTS 6 months after the TUMT and PAE procedures, measured by the International Prostate Symptom Score (IPSS). Both treatments have previously been shown to reduce LUTS with a similar post-procedure outcome in mean IPSS. However, the previous studies differed in baseline characteristics thus it is currently unknown if they perform equally well. Secondary objectives include comparison of patient reported and functional outcomes at short- and long-term follow-up. The trial importantly includes analysis of patient-reported outcome measures of satisfaction with treatment, quality of life, incontinence, erectile and ejaculatory function, as well as evaluation of uroflowmetry, prostate volume, prostate specific antigen, catheter dependency, side effects, hospital admissions and re-treatment rate.

This study is designed as a multi-centre, non-inferiority, open label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments using the randomisation module in REDCap. The primary outcome is expected to be evaluated by a 95% confidence interval against the predefined threshold of +3 points in IPSS for inferiority. Secondary outcomes will be presented descriptively and assessed by students T-test, Chi-squared test and linear mixed models. The patient reported outcomes will be obtained by standardized validated surveys and functional outcomes, side effects and re-treatment rates will be measured at 1 month, 3 months, 6 months, 1 year, 2 years and 5 years post procedure. Assuming a difference in mean IPSS after treatment of 1 point with an standard deviation (SD) of 5 and a non-inferiority margin set at the border for a clinically non-meaningful difference of 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% drop-out the study will include 220 patients. An interim analysis will be performed for every 50 cases.

TUMT and PAE are minimally invasive procedures performed in an outpatient setting that have been shown to reduce LUTS in a similar magnitude. To date there are no randomised clinical trials comparing PAE to TUMT, which is problematic as the most prominent problem with minimally invasive BPH treatment is the lack of proper selection of candidates for a specific procedure. Non-inferiority of TUMT to PAE is expected, with analysis of the secondary outcomes, the investigators aspire to contribute to a better understanding of patient selection for either treatment.

Eligibility criteria: Inclusion Criteria:

* Ability to understand and the willingness to sign an informed consent.
* Diagnosis of LUTS secondary to BPH refractory to/contraindicated for medical treatment or not patient preference.
* Severe urinary symptoms on IPSS (IPSS score ≥ 20).
* Bladder outlet obstruction (BOO) is defined by Qmax ≤ 15ml/sec, based on uroflowmetry.
* Prostate volume at minimum 50 ml measured by TRUS or MR.
* Men with prostate cancer in Active Surveillance or Watchful Waiting who have LUTS due to a large BPH component are allowed.
* Indwelling catheter or intermittent catheter is allowed. In this case baseline IPSS is 35 points.

Exclusion Criteria:

* Active bladder cancer (patients with pTa low-grade tumors are allowed).
* Previous pelvic radiation for cancer treatment.
* Bladder stones (inclusion is allowed after removal).
* Current urethral strictures or bladder neck contracture.
* Neurogenic LUTS.
* Symptomatic urinary tract infection at the time of intervention.
* Documented bacterial prostatitis in the last year.
* Severe atheromatous disease or other pathology preventing catheter-based intervention (as rated on CT angiography by an interventional radiologist).
* Allergy to iodinated contrast media.
* Renal failure defined as estimated glomerular filtration rate (eGFR) \< 35ml/min.
* High bleeding risk (spontaneous international normalized ratio (INR) \> 1.6).
* Contraindication to conscious sedation (if requested by the patient).
* Prostate median lobe defined by treating physician.
* Urethral colliculus to bladder neck length \<35mm.

Primary outcomes:
measure: Mean IPSS of the TUMT and PAE arm 6 months after the procedure
timeFrame: 6 months post-procedure.
Secondary outcomes:
measure: Mean IPSS of the TUMT and PAE arm at 3,12, 24 and 60 months after the procedure
timeFrame: 3, 12, 24 and 60 months post-procedure.
measure: Mean IPSS-QoL score of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean EQ-5D-5L score of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean BII score of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean patient satisfaction with the TUMT and PAE treatment by Likert scale 1 and 3 months after the procedure
timeFrame: 1 and 3 months post-procedure.
measure: Mean ICIQ-UI-SF scores of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean IIEF-EF scores of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean DAN-PSSsex score of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean prostate volume (PV), measured by TRUS, of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: Baseline, 3, 6, 12 and 24 months post-procedure.
measure: Mean maximum flow rate by uroflowmetry of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: Baseline, 3, 6, 12 and 24 months post-procedure.
measure: Mean voided volume by uroflowmetry of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: Baseline, 3, 6, 12 and 24 months post-procedure.
measure: Mean residual urine volume, of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: Baseline, 3, 6, 12 and 24 months post-procedure.
measure: Number of catheterization events of the TUMT and PAE arm at 3, 6, 12, 24 and 60 months after the procedure.
timeFrame: 3, 6, 12, 24 and 60 months post-procedure.
measure: Mean prostate-specific antigen (PSA) of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: 3, 6, 12 and 24 months post-procedure.
measure: Mean creatinine of the TUMT and PAE arm at 3, 6, 12 and 24 months after the procedure
timeFrame: 3, 6, 12 and 24 months post-procedure.
measure: De novo use of pharmacological LUTS treatment in the TUMT and PAE arms
timeFrame: 12, 24 and 60 months post-procedure.
measure: Surgical re-treatment in the TUMT and PAE arms
timeFrame: 12, 24 and 60 months post-procedure.
measure: Incidence of side effects of the TUMT and PAE arms during the first 3 months after the procedure
timeFrame: 3 months post-procedure.
Other outcomes:
measure: Mean procedure time for conduction of the TUMT and PAE procedures
timeFrame: procedure
Locations:
city: Copenhagen
country: Denmark
facility: Urological Research Unit, Rigshospitalet
state: Copenhagen N
city: Gentofte
country: Denmark
facility: Department of Urology, Herlev-Gentofte Hospital
state: Hellerup
city: Roskilde
country: Denmark
facility: Zealand University Hospital
Study officials:
affiliation: Urological Research Unit, Rigshospitalet
name: Andreas Røder, Prof.,MD,PhD
role: STUDY_DIRECTOR
affiliation: Department of Urology, Herlev-Gentofte Hospital
name: Mikkel M Fode, Prof.,MD,PhD
role: STUDY_DIRECTOR
References: