STONE: Tamsulosin for Urolithiasis in the Emergency Dept

• Sponsor: Andrew Meltzer (Other)
• Overall Status: Completed
• CT.gov ID: NCT00382265
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 512
• Locations: 4
• Arms: 2
• Duration (Months): 109
• Patients Per Site: 128
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Urolithiasis is a disease that effects 12% of the population and its incidence is growing. In the US there are over 1.1 million visits annually to Emergency Departments for renal colic. The disease is extremely painful, often requiring large amounts of narcotic analgesia, and results in lost work days. Moreover, up to 30% of patients may eventually require lithotripsy or surgical removal of the stone. Currently there are no medical interventions other than analgesia which are offered to patients.

Based on encouraging results from several small European clinical studies, the researchers hypothesize that the administration of tamsulosin to patients with symptomatic urolithiasis will enhance stone passage, and reduce both the time to recovery and the need for surgical intervention or lithotripsy. The researchers will conduct a study by identifying and recruiting patients presenting with urolithiasis in the emergency departments of four institutions.

A total of 500 consenting subjects will be randomly assigned to one of two groups:

1. tamsulosin for a maximum of 28 days;

2. placebo for a maximum of 28 days.

In addition, both groups will receive standard analgesic therapy.

The study team, which will be blinded to treatment status, will monitor each subject's clinical progress and outcome. The primary objectives of this study are:

1. to determine if tamsulosin is effective, and

2. to evaluate the safety of the therapy.

Another objective is to identify the most appropriate clinical subgroup(s) for treatment.

If the therapeutic benefits observed in smaller clinical studies are replicated, administration of these medications should produce several benefits, including:

1. a reduction in time to pain free recovery and hence a more rapid return to employment;

2. decreased requirements for narcotic analgesia;

3. less need for urological out-patient clinic follow-up;

4. decreased need for surgical intervention or lithotripsy; and

5. substantial cost savings.

If this therapy is beneficial, it will represent a major advance in the treatment of urolithiasis. This objective is a major stated goal of the NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Clinical Urology Program, which has a stated mission to improve the treatment of urolithiasis.

Kidney stones are a major public health issue, and one person in eight will be affected by the disease. If the hypothesis is verified, the researchers will provide the first medical therapy ever for this disease. This therapy, if effective, will reduce the amount of time a patient is off work because of the pain from the disease, and may also reduce the need for expensive and time-consuming surgical treatments.

Condition or Disease	Intervention/Treatment	Phase
Ureterolithiases	Drug: tamsulosin; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 512 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study of Tamsulosin for Urolithiasis in the Emergency Department
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tamsulosin Tamsulosin 0.4mg PO qd for 28 days	Drug: tamsulosin; tamsulosin 0.4mg po qd for 28 days
Placebo Comparator: Placebo Placebo PO qd for 28 days	Other: Placebo; placebo po qd for 28 days

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Passing Their Stone Within 28 Days by Self Report [28 days]

   Hypothesis: The administration of tamsulosin after the clinical and radiographic diagnosis of acute urolithiasis will produce an increase in the proportion of patients passing their stone within 28 days.

Secondary Outcome Measures

1. Any Pain Medication [28 days]

   Patients on any pain medication at day 28

2. Need for Surgical Intervention [28 days]

3. Crossover to Open Label Tamsulosin [28 days]

4. Confirmation of Stone Passage on CT [28 days]

5. Return to Work (if Employed) [28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥ 18 years

2. Evidence of ureterolithiasis (i.e. stone is located in ureter, not in bladder) as demonstrated on radiographic studies, specifically non-contrast spiral CT.

3. Willingness to participate and able to proceed with standard outpatient management (no personal or job-related issues, e.g. airline pilot.

4. Has a telephone in order to be contacted for follow-up.

Exclusion Criteria:

1. Patient desiring or requiring immediate surgical intervention making then not a candidate for outpatient kidney stone management.

2. Current urinary tract infection based on urine dipstick as admission and urgent procedural management are likely indicated.

3. Known anatomical genitourinary abnormalities or prior Genitourinary surgeries.

4. Positive pregnancy test making proper radiological imaging contraindicated.

5. Breastfeeding mothers.

6. History of hypersensitivity to tamsulosin.

7. Current use of alpha blockers or calcium channel blockers.

8. Current use of steroids which may have an independent effect on stone expulsion.

9. Spontaneous stone expulsion prior to enrollment.

10. Largest stone dimension ≥ 9mm assessed using radiologic imaging, being very unlikely to pass spontaneously.

11. Presence of stone in the bladder.

12. Current use of vardenafil which is tamsulosin contraindicated.

13. Ipsilateral, transplanted or solitary kidney as hospitalization may be necessary.

14. Known renal insufficiency.

15. Fever defined as >101.5°F which may indicate infection.

16. Floppy iris syndrome which is tamsulosin contraindicated.

17. Planned cataract surgery in the next 60 days which is tamsulosin contraindicated.

18. Prisoners /wards of state.

19. Prior enrollment in STONE (Candidates who are screened and found ineligible may be rescreened at a later date.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Birmingham	Birmingham	Alabama	United States	35249
2	The George Washington University Medical Center	Washington	District of Columbia	United States	20037
3	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
4	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15261

Sponsors and Collaborators

• Andrew Meltzer
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Andrew C Meltzer, MD, The George Washington University

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Sep 4, 2015

More Information

Publications

None provided.

• Responsible Party: Andrew Meltzer, Principal Investigator, George Washington University
• ClinicalTrials.gov Identifier: NCT00382265
• Other Study ID Numbers: RO1 DK71603; U01DK096037; U01DK071603; U34DK090957
• First Posted: Sep 29, 2006
• Last Update Posted: Dec 10, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Andrew Meltzer, Principal Investigator, George Washington University: urolithiasis; renal colic; kidney stones; urinary stone disease
• Additional relevant MeSH terms: Urolithiasis; Urinary Calculi; Ureterolithiasis; Ureteral Calculi; Emergencies; Tamsulosin

Study Results

Participant Flow

Arm/Group Title	Active Comparator:1	Placebo Comparator:2
Arm/Group Description	Tamsulosin 0.4mg PO tamsulosin: tamsulosin 0.4mg po qd for 28 days	Placebo tamsulosin: tamsulosin 0.4mg po qd for 28 days
Period Title: Overall Study
STARTED	267	245
COMPLETED	258	239
NOT COMPLETED	9	6

Baseline Characteristics

Arm/Group Title	Tamsulosin Group	Placebo Group	Total
Arm/Group Description	Tamsulosin 0.4mg PO tamsulosin: tamsulosin 0.4mg po qd for 28 days	Placebo for 28 days	Total of all reporting groups
Overall Participants	267	245	512
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (13.6)	39.3 (12.9)	40.6 (13.3)
Sex: Female, Male (Count of Participants)
Female	70 26.2%	69 28.2%	139 27.1%
Male	197 73.8%	176 71.8%	373 72.9%
Race/Ethnicity, Customized (Count of Participants)
Non-White Race	56 21%	54 22%	110 21.5%
Region of Enrollment (participants) [Number]
United States	267 100%	245 100%	512 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Passing Their Stone Within 28 Days by Self Report
Description	Hypothesis: The administration of tamsulosin after the clinical and radiographic diagnosis of acute urolithiasis will produce an increase in the proportion of patients passing their stone within 28 days.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Placebo
Arm/Group Description	Tamsulosin 0.4mg PO tamsulosin: tamsulosin 0.4mg po qd for 28 days	Placebo tamsulosin: tamsulosin 0.4mg po qd for 28 days
Measure Participants	258	239
Count of Participants [Participants]	128 47.9%	113 46.1%

2. Secondary Outcome

Title	Any Pain Medication
Description	Patients on any pain medication at day 28
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Placebo
Arm/Group Description	Tamsulosin 0.4mg PO tamsulosin: tamsulosin 0.4mg po qd for 28 days	Placebo pill po qd for 28 days
Measure Participants	226	210
Count of Participants [Participants]	22 8.2%	24 9.8%

3. Secondary Outcome

Title	Need for Surgical Intervention
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Placebo
Arm/Group Description	Tamsulosin 0.4mg po qd for 28 days	Placebo Pill qd for 28 days
Measure Participants	214	189
Count of Participants [Participants]	14 5.2%	13 5.3%

4. Secondary Outcome

Title	Crossover to Open Label Tamsulosin
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Placebo
Arm/Group Description	Tamsulosin 0.4mg po qd for 28 days	Placebo pill po qd for 28 days
Measure Participants	214	189
Count of Participants [Participants]	15 5.6%	14 5.7%

5. Secondary Outcome

Title	Confirmation of Stone Passage on CT
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Placebo
Arm/Group Description	Tamsulosin 0.4mg po qd for 28 days	Placebo Pill qd for 28 days
Measure Participants	122	116
Count of Participants [Participants]	102 38.2%	90 36.7%

6. Secondary Outcome

Title	Return to Work (if Employed)
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tamsulosin	Control Group
Arm/Group Description	Tamsulosin 0.4mg po qd for 28 days	Placebo pill po qd for 28 days
Measure Participants	204	188
Count of Participants [Participants]	202 75.7%	185 75.5%

Adverse Events

Time Frame	Adverse event data were collected for 90 days after each patient enrollment in the study.
Arm/Group Title	Tamsulosin		Placebo
Arm/Group Description	Tamsulosin 0.4mg po qd for 28 days		Placebo Pill po qd for 28 days
All Cause Mortality
	Tamsulosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/245 (0%)
Serious Adverse Events
	Tamsulosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/245 (0%)
Other (Not Including Serious) Adverse Events
	Tamsulosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/267 (0%)		0/245 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.