Efficacy of a Single Dose Dexamethasone in Reducing the Postembolization Syndrome in Men Undergoing Prostatic Artery Embolization for Benign Prostatic Hyperplasia

Randomized Double-blind Placebo-controlled Trial on the Efficacy of a Single Dose Dexamethasone in Reducing the Postembolization Syndrome in Men Undergoing Prostatic Artery Embolization for Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary tract symptoms (LUTS) in men. One fourth of men older than 70 have moderate to severe LUTS that impair their quality of life (QOL). Prostatic artery embolization (PAE) is a new minimally invasive technique proven effective in reducing LUTS comparable to the mainstay treatment - the transurethral resection of the prostate (TURP).

The most common side effect of PAE is a collection of inflammation-related symptoms known as the postembolization syndrome (PES). The symptoms include pelvic pain, fever, nausea, and transient worsening of LUTS (painful and difficult urination). PES is a self-limiting condition that is treated symptomatically with painkillers and antipyretics. However, PES can be so severe that the patients experience high fever, shivers, dysuria and urgency mimicking a septicemia from the urinary tract. It is a clinical challenge to avoid exposure to unnecessary antibiotics treatment in those situations. A subset of patients may need admission to the hospital for observation, especially in case of fever. Usually, PES resolves within a week after PAE. Steroids have been successfully used to reduce the incidence and severity of PES after a number of procedures in interventional radiology. The investigators postulate that steroids can have a similar effect in reducing PES after PAE. In this study, the efficacy of single high dose postprocedural dexamethasone (DEXA) administration in reducing PES after PAE will be evaluated, compared to placebo.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Hyperplasia
• Intervention / Treatment: Drug: Dexamethasone; Drug: Saline

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Petra Svarc, MD; Phone Number: +4591870618; Email: petra.svarc@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Petra Svarc, MD; Phone Number: 91870618; Email: petra.svarc@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Diagnosis of LUTS secondary to BPH refractory to/contraindicated for medical treatment or not patient preference
• Moderate to severe urinary symptoms on IPSS (IPSS score 8 or over)
• Qmax <=15ml/sec, based on flowmetry
• Unsuitable for TURP or refuses surgery
• Ability to understand and the willingness to sign an informed consent
• Prostate volume > 80 milliliters
• Men with low-risk prostate cancer (T1c, Gleason score <=6 on a maximum of 3 biopsies) who have LUTS due to a large BPH component are eligible
• Indwelling or intermittent catheter is allowed

Exclusion Criteria:

• History of bladder cancer
• Previous pelvic radiation for cancer treatment
• Current bladder stones
• Significant bladder diverticula
• Current urethral strictures or bladder neck contracture
• Neurologic conditions such as multiple sclerosis, Parkinson's disease and other neurological diseases known to affect bladder function
• Neurogenic bladder without obstruction
• Active urinary tract infection at the time of intervention unless in case of regular catheter dependence and thought to represent colonization
• 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 (eGFR < 30ml/min)
• High bleeding risk (spontaneous INR > 1.6)
• Contraindication to conscious sedation (if requested by participant)
• Allergy to dexamethasone
• Positive HIV, hepatitis B or C
• Immunological disease (except topically treated skin or respiratory diseases)
• Glaucoma
• Active peptic or duodenal ulcer
• Systemic fungal infections
• Immunosuppressive treatment (systemic)
• Current treatment of cancer (except low risk prostate cancer)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active drug; dexamethasone 24 mg i.v., single dose	Drug: Dexamethasone; The participants in the experimental group will receive a single 24 mg intravenous dose of dexamethasone immediately prior to PAE.
PLACEBO_COMPARATOR: Placebo; saline i.v., single dose	Drug: Saline; The participants in the placebo group will receive 6 ml of saline i.v. immediately prior to PAE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body temperature	Mean rectal body temperature, measured in degrees Celsius	Measured by participant on Day 2 following PAE,
Postprocedural pain	Mean postprocedural pain measured on Brief Pain Inventory Short Form (BPI-SF), score on a 0-10 scale, higher score indicates higher level of pain	During the first 5 days following PAE
Postprocedural quality of life	Mean postprocedural quality of life measured on BPI-SF, score on a 0-10 scale, higher score indicates lower quality of life	During the first 5 days following PAE

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory response markers	C-reactive protein, measured in mg/l	Measured at baseline and 2 days following PAE
Prostate specific antigen (PSA)	PSA, measured in ng/ml	Measured at baseline, 2 days, 1 month, 3 months, and 6 months following PAE
Need for postprocedural medication	Use of analgesics, antipyretics and antiemetics (frequency and dosage)	During the first 5 days following PAE
Hospital admission	Incidence of hospital admission	During the first 5 days following PAE
LUTS severity	Measured on International Prostate Symptom Score (IPSS) questionnaire, each answer is scored from 0 to 5 for a maximum score of 35 points, higher score indicates more pronounced symptoms	Measured at baseline, 2 days, 5 days, 1 month, 3 months, and 6 months following PAE
Erectile function	Measured on International Index of Erectile Function (IIEF-5) questionnaire, each answer is scored from 1 to 5 for a maximum score of 25 points, higher score indicates more pronounced symptoms	Measured at baseline, 1 month, 3 months, and 6 months following PAE
Prostate volume	Measured on transrectal US, in ml	Measured at baseline, 3 and 6 months following PAE
Peak urinary flow rate (Qmax)	Qmax, measured in ml/s	Measured at baseline, 3 and 6 months following PAE
Mean urinary flow rate (Qmean)	Qmean, measured in ml/s	Measured at baseline, 3 and 6 months following PAE
Residual urine	Residual urine, measured in ml	Measured at baseline, 3 and 6 months following PAE
Urinary tract infections	Incidence of urinary tract infections	During the first 5 days following PAE
Acute urinary retention	Incidence of acute urinary retention	During the first 5 days following PAE
Side effects of PAE	Incidence of side effects of PAE (PES excluded)	During the first 5 days following PAE
Dysuria	Incidence of dysuria	During the first 5 days following PAE
Nausea and vomiting	Incidence of nausea and vomiting	During the first 5 days following PAE
Blood glucose	Self-measured fasting blood glucose in mmol/l, only in patients with diabetes	During the first 5 days following PAE

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Lars B Lonn, MD, PhD, Rigshospitalet, Denmark; Principal Investigator: Martin A Røder, MD, PhD, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Svarc P, Stroomberg HV, Juhl Jensen R, Frevert S, Hakan Lindh M, Taudorf M, Brasso K, Lonn L, Roder MA. Efficacy of dexamethasone in reducing the postembolisation syndrome in men undergoing prostatic artery embolisation for benign prostatic hyperplasia: protocol for a single-centre, randomised, double-blind, placebo-controlled trial-the 'DEXAPAE' study. BMJ Open. 2021 Nov 1;11(11):e047878. doi: 10.1136/bmjopen-2020-047878.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (ACTUAL): October 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Prostatic artery embolization; Benign prostatic hyperplasia; Postembolization syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: DEXAPAE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The results of this trial will be submitted for publication in a peer reviewed journal, in addition to reports at appropriate specialist conferences. The results of the trial will be disseminated regardless of the direction of effect.

The investigators intend to share de-identified individual participant data that underlie the results reported in the published article following reasonable requests to the principal investigator, and if in accordance with Danish law.

• IPD Sharing Time Frame: Data will be made available beginning 9 months and ending 36 months after article publication.
• IPD Sharing Access Criteria: Data will be made available to qualified scientific researchers who provide a methodologically sounds proposal following reasonable requests to the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No