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Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03229889
Recruitment Status : Unknown
Verified August 2018 by Jaime Landman, University of California, Irvine.
Recruitment status was:  Enrolling by invitation
First Posted : July 26, 2017
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
Jaime Landman, University of California, Irvine

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.


Condition or disease Intervention/treatment Phase
Nephrolithiasis Drug: Cialis 5Mg Tablet Drug: Flomax 0.4Mg Capsule Combination Product: Cialis + Flomax Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: Patients will be randomized into 1 of 4 groups: Flomax + Placebo, Cialis + Placebo, Cialis + Flomax, Placebo + Placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Medication Facilitated Ureteral Access Sheath Deployment During Ureteroscopy and Endoscopic-Guided Percutaneous Nephrolithotomy: A Randomized Double-Blind Placebo Controlled Trial of Tadalafil, Tamsulosin and Combination
Actual Study Start Date : June 7, 2017
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Stones

Arm Intervention/treatment
Active Comparator: Flomax + Placebo
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
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.
Other Name: Tamsulosin

Active Comparator: Cialis + Placebo
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 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.
Other Name: Tadalafil

Active Comparator: Cialis + Flomax
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
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.
Other Names:
  • Tamsulsoin
  • Tadalafil

Placebo Comparator: Placebo + Placebo
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
This is plant cell based pill that contains no active ingredient. Patients will be asked to 1 pill for 7 days prior to surgery.
Other Name: Inactive Drug




Primary Outcome Measures :
  1. Passage of 16F Access Sheath [ Time Frame: This will be assessed immediately post-op per patient. ]
    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.


Secondary Outcome Measures :
  1. Injury [ Time Frame: This will be assessed immediately post-op per patient. ]
    Assessment of ureteral wall injury as defined by the post-ureteroscopic lesion score (PULS) as recorded during removal of the access sheath at the end of the surgical procedure

  2. Complications [ Time Frame: This will be assessed post-op per patient. ]
    Intraoperative complications will be recorded as defined by the Clavien-Dindo scale.

  3. Adverse events [ Time Frame: This will be assessed from the first day patients take the drugs until 1 weeks post-op. ]
    Incidence of adverse events with medications versus placebo as obtained during history on day of surgery, and during follow-up visit 1 week later

  4. Stone-free status [ Time Frame: This will be assessed immediately post-op as well as 3 months post-op. ]
    Stone free status as determined by low dose stone protocol CT scan per usual post-operative follow-up.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

- 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
  • Patients with high risk cardiovascular disease: left ventricular outflow obstruction, MI in last 90 days, unstable angina, stroke in last 6 months, uncontrolled arrhythmias
  • Patients with renal impairment (CrCl < 30 mL/min) or severe hepatic impairment (Child-Pugh score ≥ 10)
  • Patients using CYP3A4 inhibitors such as clarithromycin, ritonavir, ketoconazole, or Iitraconazole

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03229889


Locations
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United States, California
UC Irvine Health
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
Investigators
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Principal Investigator: Jaime Landman, MD UC Irvin Health
Publications:

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Responsible Party: Jaime Landman, Chair Department of Urology, University of California, Irvine
ClinicalTrials.gov Identifier: NCT03229889    
Other Study ID Numbers: 2016-3281
First Posted: July 26, 2017    Key Record Dates
Last Update Posted: August 23, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Jaime Landman, University of California, Irvine:
Access Sheath
PCNL
Percutaneous Nephrolithotomy
Ureteroscopy
Alpha Blocker
Flomax
PDE-5 Inhibitor
Cialis
Phosphodiesterase Inhibitor
Additional relevant MeSH terms:
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Nephrolithiasis
Kidney Calculi
Kidney Diseases
Urologic Diseases
Urolithiasis
Urinary Calculi
Calculi
Pathological Conditions, Anatomical
Tadalafil
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
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors