Tamsulosin for Urolithiasis in the Emergency Dept (STONE)

• Sponsor: Andrew Meltzer
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Andrew Meltzer, George Washington University

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

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Study Type :	Interventional (Clinical Trial)
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 :	January 2008
Actual Primary Completion Date :	February 1, 2017
Actual Study Completion Date :	February 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 [ Time Frame: 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 [ Time Frame: 28 days ]
   Patients on any pain medication at day 28
2. Need for Surgical Intervention [ Time Frame: 28 days ]
3. Crossover to Open Label Tamsulosin [ Time Frame: 28 days ]
4. Confirmation of Stone Passage on CT [ Time Frame: 28 days ]
5. Return to Work (if Employed) [ Time Frame: 28 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35249
United States, District of Columbia
The George Washington University Medical Center
Washington, District of Columbia, United States, 20037
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261

Sponsors and Collaborators

Andrew Meltzer

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

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

  Study Documents (Full-Text)

Documents provided by Andrew Meltzer, George Washington University:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] September 4, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Meltzer AC, Burrows PK, Wolfson AB, Hollander JE, Kurz M, Kirkali Z, Kusek JW, Mufarrij P, Jackman SV, Brown J. Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones: A Randomized Clinical Trial. JAMA Intern Med. 2018 Aug 1;178(8):1051-1057. doi: 10.1001/jamainternmed.2018.2259.

Burrows PK, Hollander JE, Wolfson AB, Kurz MC, Richards L, DiFiore S, Watts P, Patkar N, Brown J, Jackman S, Kirkali Z, Kusek JW, Michel C, Meltzer AC; STONE Study Investigators. Design and challenges of a randomized clinical trial of medical expulsive therapy (tamsulosin) for urolithiasis in the emergency department. Contemp Clin Trials. 2017 Jan;52:91-94. doi: 10.1016/j.cct.2016.11.010. Epub 2016 Nov 23.

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Responsible Party:	Andrew Meltzer, Principal Investigator, George Washington University
ClinicalTrials.gov Identifier:	NCT00382265 History of Changes
Other Study ID Numbers:	RO1 DK71603; U01DK096037 ( U.S. NIH Grant/Contract ); U01DK071603 ( U.S. NIH Grant/Contract ); U34DK090957 ( U.S. NIH Grant/Contract )
First Posted:	September 29, 2006
Results First Posted:	December 10, 2018
Last Update Posted:	December 10, 2018
Last Verified:	November 2018

Keywords provided by Andrew Meltzer, George Washington University:

urolithiasis; renal colic; kidney stones; urinary stone disease

Additional relevant MeSH terms:

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Emergencies; Urolithiasis; Ureterolithiasis; Ureteral Calculi; Disease Attributes; Pathologic Processes; Urologic Diseases; Ureteral Diseases; Urinary Calculi; Calculi	Pathological Conditions, Anatomical; Tamsulosin; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents