Efficacy and Safety of Silodosin in the Treatment of Natural Expulsion in Patients With Ureteral Stones (STONE)

A 4-week, Double-blind, Randomized, Comparative and Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Silodosin in the Treatment of Natural Expulsion in Patients With Ureteral Stones.

A lower ureteral calculus, which measures 5 millimeters and less, may be easily expelled by symptomatic therapy. Actually, it has about a 50% chance of successful expulsion.

However, a complication such as urinary tract infection or hydronephrosis or persistent pain may occur before it is expelled. Thus, it is imperative to minimize the occurrence of complications in the process of expectant treatment and also to reduce the time required to expel calculi.

Pharmacotherapy is to relieve ureteral obstruction and thus to expel urinary calculi easily.

This clinical trial is to evaluate the efficacy of silodosin, a selective α1A-blocker, on calculous expulsion in expectant treatment for patients with lower and mid ureteral calculi.

Study Overview

• Status: Completed
• Conditions: Ureteral Stone
• Intervention / Treatment: Drug: Silodosin; Drug: Placebo

Detailed Description

Lower and mid ureteral calculi, accounting for approximately 70% of ureteral calculi, has a high chance of successful treatment thanks to ureteroscopic lithotripsy or extracorporeal shock wave lithotripsy (ESWL)1-3), but at the same time have problems of postprocedural complications and high expenses4). A lower ureteral calculus, which measures 5 millimeters and less, may be easily expelled by symptomatic therapy. Actually, it has about a 50% chance of successful expulsion5). However, a complication such as urinary tract infection or hydronephrosis or persistent pain may occur before it is expelled. Thus, it is imperative to minimize the occurrence of complications in the process of expectant treatment and also to reduce the time required to expel calculi.

It has been recently reported that pharmacotherapy is adhibited to the expulsion of urinary calculi and the relief of pain. The migration of ureteral calculi is influenced by both the calculus and the ureter. In the case of the calculus, size, shape, number and location influence it. In regard to the ureter, it is significantly influenced by the cramp of the ureteral smooth muscle, the edema of the ureteral submucosa, the pain caused by the calculus and the activities of adrenoreceptors6).

Pharmacotherapy is to relieve ureteral obstruction and thus to expel urinary calculi easily. Ureteral obstruction, caused by urinary calculi, obtunds ureteral peristalsis but strengthens ureteral contraction, which may cause urinary retention or regurgitation7-8). In this connection, studies have been conducted as to methods to reduce abnormal urinary reaction caused by urinary calculi and to smoothen uroflow. Currently, hormone drugs including hydroxyprogesterone, prostaglandin synthetase inhibitors, calcium-channel antagonists, α1-blockers and steroid drugs are used to expel urinary calculi and to suppress pain. The guidelines on urinary calculi, drawn up in 2007, recommend using α-blockers as they are superior to other drugs in efficacy9-12).

The drug to be used in this clinical trial, silodosin, was registered under the proprietary name of 'THRUPAS® Capsule 4mg' and is being marketed after being authorized by Korea Food and Drug Administration (FDA), which selectively acts on the α1A-adrenoreceptor.

This clinical trial is to evaluate the efficacy of silodosin, a selective α1A-blocker, on calculous expulsion in expectant treatment for patients with lower and mid ureteral calculi.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-746
    • Kangbuk Samsung Medical Center
  • Seoul, Korea, Republic of, 139-707
    • Inje Univ. Sanggye Paik Hospital
  • Seoul, Korea, Republic of, 139-711
    • Eulji General Hospital
  • Gyonggi-Do
    • Goyang-Si, Gyonggi-Do, Korea, Republic of, 410-719
      • NHIC Ilsan Hospital
    • Goyang-Si, Gyonggi-Do, Korea, Republic of, 412-270
      • Myongji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or female patients aged 20 and over
• Patients having ureteral calculi located mid or lower ureter on abdominal radiograms or excretory urograms or non-enhanced computed tomograms.
• Patients whose calculi measure 10 millimeters and less.
• Patients who voluntarily decided to take part in this clinical trial and gave written consent.

Exclusion Criteria:

• Patients who do not want to undergo expectant treatment
• Female patients who are pregnant or nursing
• Patients with febrile urinary tract infection or severe hydronephrosis or ulcerative diseases or hypotension.
• Patients with severe hepatic dysfunction(e.g. hepatic failure, hepatic cirrhosis, icterus, hepatoma)
• Patients who take α-blocker or α/β-blockers or calcium-channel blockers or steroid drugs
• Patients with multiple ureteral calculi
• Patients whose urinary tracts are anatomically deformed or stenosed
• Patients who underwent invasive operations on their ureters before
• Patients whose blood creatinine levels are 2mg/dL and over
• Patients who are hypersensitive to silodosin
• Patients who take part in clinical trials other than this one
• Patients judged to be inappropriate for this clinical trial by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Silodosin; 8mg QD	Drug: Silodosin; Drug: silodosin dosage form : capsule dosage : placebo 4mg*2 (8mg) frequency and duration : QD, 4weeks Arms: Placebo
Placebo Comparator: Placebo; 8mg QD	Drug: Placebo; dosage form : capsule dosage : placebo 4mg*2 (8mg) frequency and duration : QD, 4weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expulsion rate of stones	1 week, 2 weeks, 4 weeks to visit and inspected. (Last visit four weeks) Results when the exhaust is used.	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Stone expulsion time	every 1 week or 2 weeks
Migration distance of stone	every 1 week or 2 weeks
Frequency of administration of oral or injectable analgesics	every 1 week or 2 weeks
Number of cases where subjects visited ER due to uncontrolled pains	every 1 week or 2 weeks

Collaborators and Investigators

• Sponsor: JW Pharmaceutical
• Investigators: Principal Investigator: Gwan-Joong Joo, Ph.D, Kangbuk Samsung Hospital; Principal Investigator: Tae-Yoong Jeong, Ph.D, Myongji Hospital; Principal Investigator: Young-Sik Kim, Ph.D, National Health Insurance Service Ilsan Hospital; Principal Investigator: Tak-Geun Yoo, Ph.D, Eulji Central Hospital; Principal Investigator: Jae-Yong Jeong, Ph.D, Inje University

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 10, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Estimate): November 20, 2013
• Last Update Submitted That Met QC Criteria: November 18, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Pathological Conditions, Anatomical; Ureteral Diseases; Urolithiasis; Urinary Calculi; Calculi; Ureteral Calculi; Ureterolithiasis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Silodosin
• Other Study ID Numbers: CWP-SDS-404