Treatment of Symptoms After Stent Placement for Urinary Tract Obstruction

Combination Versus Monotherapy With Alpha Blocker and Anticholinergics to Relieve Urinary Stent Symptoms

The purpose of this study is to determine whether combination therapy with Tolterodine ER and Tamsulosin is more effective than monotherapy with tamsulosin alone in reducing stent symptoms. The second purpose is to determine if people have less stent discomfort if they take these medications starting 2 weeks before the stent is placed

The investigators hope to show that the addition of Tolterodine ER to Tamsulosin will provide added benefits in reducing stent symptoms in patients who have had unilateral placement of a ureteral stent.

Study Overview

• Status: Completed
• Conditions: Ureteral Obstruction
• Intervention / Treatment: Drug: Tamsulosin; Drug: Tolterodine ER

Detailed Description

The investigators aim to show that the addition of Tolterodine ER to Tamsulosin will provide added benefits in ameliorating stent-related symptoms in participants who have had unilateral placement of a ureteral stent for urolithiasis. This objective will be assessed by determining the mean difference in the urinary symptom index domain of the Urinary Stent Symptom Questionnaire, which is a validated tool used to assess stent symptoms. The investigators suggest that a 15% further decrease in the index score in the experimental group, compared to the control group would represent a clinically significant improvement in urinary symptoms, based on the prior studies evaluating lower urinary tract symptoms in patients with stents. The investigators hypothesize that combination therapy with Tamsulosin and Tolterodine ER will yield greater symptom relief than tamsulosin alone.

Initially, a 7-day design (medical starts 7 days before stent insertion) was conducted to determine whether combination therapy with Tolterodine ER and Tamsulosin is more effective than monotherapy with tamsulosin alone in reducing stent symptoms.

Previous studies showed that tolterodine ER therapy significantly reduces urinary symptoms by week 4 of medication therapy. Given the evidence that tolterodine ER requires a longer duration to have maximum benefit, in the second phase, investigators increased the duration of medication to start 2 weeks prior to surgery and continued for 7 days after surgery, for a total of 21 days of medication, to test whether combination therapy is more effective than monotherapy in reducing stent symptoms

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with unilateral ureteral stent placement for urolithiasis

Exclusion Criteria:

1. Pre-existing lower urinary tract symptoms
2. Active urinary tract infection

3. Contraindication to anticholinergic medication

   1. Prior hypersensitivity or allergy to tolterodine
   2. Patients with severe hepatic impairment (Child-Pugh Class C)
   3. Patients with uncontrolled close (narrow) angle glaucoma
   4. Patients with urinary retention
4. Current anticholinergic use
5. Chronic pelvic pain syndromes (e.g. acute/chronic prostatitis, interstitial cystitis)
6. Women who are pregnant or nursing
7. Under 18 years of age
8. Prior hypersensitivity or allergy to tolterodine
9. Patients with severe hepatic impairment (Child-Pugh Class C)
10. Patients with uncontrolled close (narrow) angle glaucoma
11. Patients with urinary retention
12. Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tamsulosin plus placebo 7-day treatment; Tamsulosin is a selective α1a-blocker (FlomaxTM), generic since 2009. It is an antagonist of α1-mediated contraction of prostate, bladder and proximal urethral smooth muscle, and as such, reduces urethral pressure and resistance, bladder outlet resistance, bladder hyperactivity, and consequently lower urinary tract symptoms.	Drug: Tamsulosin; 0.4 mg by mouth once per day.; Other Names: Flomax (TM)
Experimental: Tamsulosin plus Tolterodine ER 7-day treatment; Tamsulosin is a selective α1a-blocker (FlomaxTM), generic since 2009. It is an antagonist of α1-mediated contraction of prostate, bladder and proximal urethral smooth muscle, and as such, reduces urethral pressure and resistance, bladder outlet resistance, bladder hyperactivity, and consequently lower urinary tract symptoms. Tolterodine ER is an anticholinergic agent, which is used as one of the first line agents for detrusor overactivity.	Drug: Tamsulosin; 0.4 mg by mouth once per day.; Other Names: Flomax (TM); Drug: Tolterodine ER; 4 mg by mouth once a day.; Other Names: Detrol (TM)
Active Comparator: Tamsulosin plus placebo 21-day treamtnet; Tamsulosin is a selective α1a-blocker (FlomaxTM), generic since 2009. It is an antagonist of α1-mediated contraction of prostate, bladder and proximal urethral smooth muscle, and as such, reduces urethral pressure and resistance, bladder outlet resistance, bladder hyperactivity, and consequently lower urinary tract symptoms.	Drug: Tamsulosin; 0.4 mg by mouth once per day.; Other Names: Flomax (TM)
Experimental: Tamsulosin plus Tolterodine ER 21-day treatment; Tamsulosin is a selective α1a-blocker (FlomaxTM), generic since 2009. It is an antagonist of α1-mediated contraction of prostate, bladder and proximal urethral smooth muscle, and as such, reduces urethral pressure and resistance, bladder outlet resistance, bladder hyperactivity, and consequently lower urinary tract symptoms. Tolterodine ER is an anticholinergic agent, which is used as one of the first line agents for detrusor overactivity.	Drug: Tamsulosin; 0.4 mg by mouth once per day.; Other Names: Flomax (TM); Drug: Tolterodine ER; 4 mg by mouth once a day.; Other Names: Detrol (TM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ureteral Stent Symptom Questionnaire Score Up to 24 Hours Prior to Stent Insertion	The ureteral stent symptom questionnaire contains 36 items from the 5 subscales: urinary index (11-items, total range of scores 11-54, The range of the mean score is 1-4.9), pain (8-items, total range of scores 5-27. Two items are not included in the calculation. The range of the mean score is 0.83-4.5), general health (6-items, total range of scores 4-28. The range of the mean score is 0.67-4.67), work (if stent influence patients work; 7-items, total range of scores 3-15. Four items are not included in the calculation. The range of the mean score is 1-5), and sexual matters (4-items, total range of scores 2-10. Two items are not included in the calculation. The range of the mean score is 1-5). In all cases, higher scores indicate worse outcomes. The score for each subscale is summed and divided by the number of items on the subscale. The group mean for each subscale is reported, the score is not normalized.	Up to 24 hours prior to stent insertion
Ureteral Stent Symptom Questionnaire Score	The ureteral stent symptom questionnaire contains 36 items from the 5 subscales: urinary index (11-items, total range of scores 11-54, The range of the mean score is 1-4.9), pain (8-items, total range of scores 5-27. Two items are not included in the calculation. The range of the mean score is 0.83-4.5), general health (6-items, total range of scores 4-28. The range of the mean score is 0.67-4.67), work (if stent influence patients work; 7-items, total range of scores 3-15. Four items are not included in the calculation. The range of the mean score is 1-5), and sexual matters (4-items, total range of scores 2-10. Two items are not included in the calculation. The range of the mean score is 1-5). In all cases, higher scores indicate worse outcomes. The score for each subscale is summed and divided by the number of items on the subscale. The group mean for each subscale is reported, the score is not normalized.	42-48 hours post-stent insertion
Ureteral Stent Symptom Questionnaire Score 5-7 Days Post-stent Insertion	The ureteral stent symptom questionnaire contains 36 items from the 5 subscales: urinary index (11-items, total range of scores 11-54, The range of the mean score is 1-4.9), pain (8-items, total range of scores 5-27. Two items are not included in the calculation. The range of the mean score is 0.83-4.5), general health (6-items, total range of scores 4-28. The range of the mean score is 0.67-4.67), work (if stent influence patients work; 7-items, total range of scores 3-15. Four items are not included in the calculation. The range of the mean score is 1-5), and sexual matters (4-items, total range of scores 2-10. Two items are not included in the calculation. The range of the mean score is 1-5). In all cases, higher scores indicate worse outcomes. The score for each subscale is summed and divided by the number of items on the subscale. The group mean for each subscale is reported, the score is not normalized.	5-7 days post-stent insertion
Ureteral Stent Symptom Questionnaire Score Up to 24 Hours After Stent Removal	The ureteral stent symptom questionnaire contains 36 items from the 5 subscales: urinary index (11-items, total range of scores 11-54, The range of the mean score is 1-4.9), pain (8-items, total range of scores 5-27. Two items are not included in the calculation. The range of the mean score is 0.83-4.5), general health (6-items, total range of scores 4-28. The range of the mean score is 0.67-4.67), work (if stent influence patients work; 7-items, total range of scores 3-15. Four items are not included in the calculation. The range of the mean score is 1-5), and sexual matters (4-items, total range of scores 2-10. Two items are not included in the calculation. The range of the mean score is 1-5). In all cases, higher scores indicate worse outcomes. The score for each subscale is summed and divided by the number of items on the subscale. The group mean for each subscale is reported, the score is not normalized.	Up to 24 hours after stent removal. Removal will occur 5 to 7 days after insertion.

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Stephen Nakada, MD, Univeristy of Wisconsin

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): March 30, 2018

Study Registration Dates

• First Submitted: November 29, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Tamsulosin; Tolterodine; Ureteral Obstruction
• Additional Relevant MeSH Terms: Urologic Diseases; Ureteral Diseases; Ureteral Obstruction; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin; Tolterodine Tartrate
• Other Study ID Numbers: 2017-0755; 2012-0279 (Other Identifier: HS IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No