Silodosin, Tadalafil Alone vs. Silodosin Plus Tadalafil as MET for Lower Ureteric Stones

Efficacy of Silodosin, Tadalafil Alone Versus Silodosin Plus Tadalafil as Medical Expulsive Therapy for Lower Ureteric Stones: A Prospective Randomized Placebo Controlled Study

This study will compare the efficacy of silodosin, tadalafil versus silodosin plus tadalafil as Medical Expulsive Therapy (MET) for lower ureteric stones.

Study Overview

• Status: Completed
• Conditions: Lower Ureteric Stones; Medical Expulsive Therapy; Tadalafil; Silodosin
• Intervention / Treatment: Drug: Placebo; Drug: Silodosin; Drug: Tadalafil; Drug: Silodosin and Tadalafil

Detailed Description

The global incidence of urolithiasis, a disease with a high recurrence rate, is increasing. Urolithiasis is one of the most common disorders of the urinary tract with a lifetime prevalence of up to 15% with men affected three times more than women.

Urolithiasis causes recurrent stone formers to experience a decline in quality of life, and there is an increasing socioeconomic burden associated with the management of urolithiasis. Improved quality of life may also have increased its prevalence. A significant proportion, about 1/5th of urinary tract stones, is found in the ureter, of which 2/3rd is seen in the distal ureter. Initially, a colicky pain of various grades presents with ureteric stone. It is one of the most common problems that compel a patient to an emergency room.

Methods to manage ureteral stones include conservative treatment, pharmacological treatment (e.g., medical expulsive therapy), shock wave lithotripsy, and surgical treatment. Thus, urologists must select the appropriate treatment for each patient (i.e., non-surgical or surgical). Today, medical expulsive therapy has become the most used modality of treatment for urolithiasis. During this treatment, the ureter smooth muscle is treated via various drugs by different mechanisms.

Blocking alpha-(α-) 1 adrenergic receptor, especially in the distal third decreases basal smooth muscle contraction and causes propulsive antegrade peristalsis helping stone expulsion. By increasing the intraureteral pressure gradient around the stone, alpha-1 adrenergic receptor antagonists eject distal ureteral stones.

Significant pathological changes can occur when ureteric stones are impacted. +is can cause an inflammatory reaction with mucosal edema which could further worsen the ureteric obstruction, increasing the risk of impaction and retention. However, selective alpha-1 blockers, such as tamsulosin and silodosin, have been the treatment of choice, with proven efficacy in multiple clinical trials. Silodosin is a more selective α-1A adrenoceptor blocker with a better stone expulsion rate than tamsulosin.

Recently, a newer Phosphodiesterase type 5 inhibitor, tadalafil, has shown action on the nitric oxide-cyclic guanosine monophosphate signaling pathway of smooth muscles, resulting in increased levels of cyclic guanosine monophosphate, causing ureteric relaxation.

Due to its smooth muscle relaxation mechanism, tadalafil has received US Food and Drug Administration approval to treat many urinary tract diseases. Therefore, the combination of silodosin and tadalafil drugs is aimed to facilitate stone passage by better ureteric relaxation and reducing intramural ureter pressure. Although there have been few similar studies using various combinations, comparing the efficacy of silodosin and tadalafil vs. silodosin are very few, and these studies have taken longer duration of treatment (4 to 6 weeks) which might have affected the outcome.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Benha, Egypt
    • Benha University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 168 patients aged >18 years old.
• Both sexes.
• Diagnosed with lower ureteric stone from 5mm to 10mm in size.

Exclusion Criteria:

• Patients with multiple or bilateral ureteric stones
• single kidney or impairment of renal function
• Urinary tract infection (UTI)
• Marked hydronephrosis
• Patients presenting with severe intractable pain and requiring emergency intervention
• Any urologic anomalies or history of ureteral surgery
• Pregnancy
• Pediatric populations
• Ischemic heart disease
• Congestive cardiac failure
• Complicated hypertension
• Patients on concomitant treatment with nitrates or calcium channel blockers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Patients in this group will receive placebo treatment once daily.	Drug: Placebo; Patients will receive placebo treatment once daily.
Experimental: Silodosin group; Patients will receive Silodosin 8 mg once daily.	Drug: Silodosin; Patients will receive Silodosin 8 mg once daily.
Experimental: Tadalafil group; Patients will receive Tadalafil 5 mg once daily.	Drug: Tadalafil; Patients will receive Tadalafil 5 mg once daily.
Experimental: Silodosin and Tadalafil; Patients will receive Silodosin 8mg in combination with Tadalafil 5 mg once daily.	Drug: Silodosin and Tadalafil; Patients will receive Silodosin 8mg in combination with Tadalafil 5 mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stone expulsion rate	Stone expulsion rate will be recorded	Intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stone expulsion time	Stone expulsion time will be recorded	Intraoperatively
Amount of analgesia used	The amount of analgesia used will be recorded	Intraoperatively

Collaborators and Investigators

• Sponsor: Benha University

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): August 30, 2022

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Pathological Conditions, Anatomical; Ureteral Diseases; Urolithiasis; Urinary Calculi; Calculi; Ureteral Calculi; Ureterolithiasis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tadalafil; Silodosin
• Other Study ID Numbers: Rc 22-3-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study will be available under a reasonable request of the corresponding author
• IPD Sharing Time Frame: One year after the end of the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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