Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment

NCT03229889 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 20163281
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Extensive literature exists on the use of alpha-blocker medications for the removal of kidney stones. Alpha blockers relax certain muscles and help small blood vessels remain open. They work by keeping the hormone norepinephrine (noradrenaline) from tightening the muscles in the walls of smaller arteries and veins, which causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure. There are studies that demonstrate alpha-blockers decrease ureteral pressure and help the ureter "relax." Recent studies have shown that phosphodiesterase inhibitors may also help with ureteral stone passing. A phosphodiesterase inhibitor is a drug that blocks an enzyme that inhibits relaxation of smooth muscle. This means that it can help smooth muscle, such as the muscle that lines the ureter, to relax. While ureteral relaxation is helpful in the passage of ureteral stones, our study seeks to use this finding by pretreating participants with an older generation alpha blocker or a phosphodiesterase inhibitor prior to passage of a ureteral access sheath in cases in which ureteroscopy is being used to approach a ureteral or renal stone. By relaxing the ureter, it is possible that a larger access sheath can be safely placed. This may allow for facilitating passage of the ureteroscope and extraction of stone fragments while precluding the development of potentially damaging intrarenal pressure from the flow of irrigant. The ureteral access sheath also protects the ureter from damage during the procedure. Placement of the largest access sheath possible is helpful in that larger stone fragments can be retrieved, the flow of irrigant is improved, and the surgical field is kept clear of blood or debris. To date, nobody has studied whether use of an uro-selective alpha blocker, alone, or in combination with a 5 phosphodiesterase inhibitor will result in passage of larger access sheaths. In this study participants will be randomized into 1 of 4 categories: Flomax (alpha-blocker), Cialis (5-phosphodiesterase inhibitor), a combination of the 2, or a placebo arm. In this study the placebo, or no active drug, is the current standard of care and will serve as a control from the other 3 groups.

Conditions

Nephrolithiasis

Keywords

Access Sheath; PCNL; Percutaneous Nephrolithotomy; Ureteroscopy; Alpha Blocker; Flomax; PDE-5 Inhibitor; Cialis; Phosphodiesterase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Passage of 16F Access Sheath

  Our primary objective is to assess the ability of a uroselective alpha-blocker (tamsulosin) and PDE-5 inhibitor (tadalafil), either alone or in combination will facilitate the passage of a 16F ureteral access sheath. Successful deployment will be defined as passage of the 16F ureteral access sheath into the proximal ureter or ureteropelvic junction. Difficulty in passing a 16F ureteral access sheath will be defined as a "failure". In this situation, we will place smaller ureteral access sheath (i.e. 11F or 14F), or opt to place a stent to dilate the ureter, and plan for surgery in the future; this is standard of care.

  This will be assessed immediately post-op per patient.

Secondary Outcomes (4)

• Injury

  This will be assessed immediately post-op per patient.

• Complications

  This will be assessed post-op per patient.

• Adverse events

  This will be assessed from the first day patients take the drugs until 1 weeks post-op.

• Stone-free status

  This will be assessed immediately post-op as well as 3 months post-op.

Study Arms (4)

Flomax + Placebo

ACTIVE COMPARATOR

Patients will be prescribed Flomax 0.4Mg Capsule and given a bottle of placebo. They will be instructed to take 1 of each pill for the seven days prior to their surgery.

Drug: Flomax 0.4Mg Capsule

Cialis + Placebo

ACTIVE COMPARATOR

Patients will be prescribed Cialis 5Mg tablet and given a bottle of placebo. They will be instructed to take 1 of each pill for the seven days prior to their surgery.

Drug: Cialis 5Mg Tablet

Cialis + Flomax

ACTIVE COMPARATOR

Patients will be prescribed .4mg of Flomax and 5mg of Cialis. They will be instructed to take 1 of each pill for the seven days prior to their surgery.

Combination Product: Cialis + Flomax

Placebo + Placebo

PLACEBO COMPARATOR

Given 2 bottles of placebo. They will be instructed to take 1 of each pill for the seven days prior to their surgery.

Drug: Placebo

Interventions

Cialis 5Mg Tablet DRUG

Cialis is a PDE-5 inhibitor that has been shown to relax smooth muscle. Patients will be asked to 1 pill for 7 days prior to surgery.

Also known as: Tadalafil

Cialis + Placebo

Flomax 0.4Mg Capsule DRUG

Tamsulosin is an alpha-blocker that has been shown to relax smooth muscle in the genitourinary system. Patients will be asked to 1 pill for 7 days prior to surgery.

Also known as: Tamsulosin

Flomax + Placebo

Cialis + Flomax COMBINATION_PRODUCT

Cialis is a PDE-5 inhibitor that has been shown to relax smooth muscle. Tamsulosin is an alpha-blocker that has been shown to relax smooth muscle in the genitourinary system. A combination of these two drugs may increase the relaxation effects in the ureter. Patients will be asked to 1 of each pill for 7 days prior to surgery.

Also known as: Tamsulsoin, Tadalafil

Cialis + Flomax

Placebo DRUG

This is plant cell based pill that contains no active ingredient. Patients will be asked to 1 pill for 7 days prior to surgery.

Also known as: Inactive Drug

Placebo + Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing percutaneous nephrolithotomy (PCNL) or ureteroscopy (URS) for renal or proximal ureteral urolithiasis
• A documented sterile urine culture within 1-2 weeks of the procedure
• ≥ 18 years old
• Ability to understand and the willingness to sign a written informed consent

You may not qualify if:

• \- Patients \< 18-years-old
• Presence of ureteral stent or nephrostomy tube prior to scheduled procedure
• Patients requiring open, endoscopic, or laparoscopic procedure in the same setting as the intended URS or PCNL
• Planned concurrent bilateral endoscopic ureteral procedures
• Patients currently taking alpha-blockers within 14 days of surgery
• Patients taking PDE-5 inhibitors within 14 days of surgery
• Pregnant women
• Active urinary tract infection (UTI) or uncontrolled HIV
• Uncorrected coagulopathy
• Patients who cannot stop their blood thinners, and/or non-steroidal anti-inflammatory medications 5-7 days prior to the procedure
• Patients allergic to tamsulosin or tadalafil
• Patients with upcoming cataract surgery due to risk of floppy iris syndrome
• Patients with history of priapism
• Patients with hereditary retinitis pigmentosa
• Patients concurrently using nitrates for myocardial infarction (MI) or angina

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

UC Irvine Health

Orange, California, 92868, United States

Location

Related Publications (24)

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MeSH Terms

Conditions

Nephrolithiasis

Interventions

Tadalafil; Tablets; Tamsulosin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Dosage Forms; Pharmaceutical Preparations; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Jaime Landman, MD

  UC Irvin Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both patients and treating surgeons (who are also on the study team) will be blinded. None physician researchers will be unblinded to tract and randomize patients.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair Department of Urology

Model Details: Patients will be randomized into 1 of 4 groups: Flomax + Placebo, Cialis + Placebo, Cialis + Flomax, Placebo + Placebo.

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: July 26, 2017
• Study Start: June 7, 2017
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: February 17, 2026

Record last verified: 2024-08

Locations

US (1)