Clinical trial NCT01533389: Efficacy and Safety of Silodosin in the Treatment of Natural Expulsion in Patients With Ureteral Stones
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ureteral Stone
Lead sponsor: JW Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2012-02-15
Enrollment: 114
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Expulsion rate of stones
timeFrame: 4 weeks
Secondary outcomes:
measure: Stone expulsion time
timeFrame: every 1 week or 2 weeks
measure: Migration distance of stone
timeFrame: every 1 week or 2 weeks
measure: Frequency of administration of oral or injectable analgesics
timeFrame: every 1 week or 2 weeks
measure: Number of cases where subjects visited ER due to uncontrolled pains
timeFrame: every 1 week or 2 weeks
Other outcomes:
Locations:
city: Goyang-Si
country: Korea, Republic of
facility: NHIC Ilsan Hospital
state: Gyonggi-Do
city: Goyang-Si
country: Korea, Republic of
facility: Myongji Hospital
state: Gyonggi-Do
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Inje Univ. Sanggye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
Study officials:
affiliation: Kangbuk Samsung Hospital
name: Gwan-Joong Joo, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Myongji Hospital
name: Tae-Yoong Jeong, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Health Insurance Service Ilsan Hospital
name: Young-Sik Kim, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Eulji Central Hospital
name: Tak-Geun Yoo, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Inje University
name: Jae-Yong Jeong, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: