Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) as Medical Expulsive Therapy in Distal Ureteral Stones

Role of Phosphodiesterase 5 Inhibitors (PDE5i) (Sildenafil) in Management of Distal Ureteral Stone

Urolithiasis is one of the most common urological diseases. The risk of urolithiasis is estimated to be between 5% and 12% all over the world with increased incidence in male rather than female (2:1) respectively . Ureteral stones account for 20% from all urinary tract stones, more than 70% of the ureteral stones found in the lower third of the ureter . The incidence of urinary stones has been increasing day by day. Medical expulsive therapy (MET) of ureteral stones is the investigators' concern in this study. Stone location, size, number, ureteral spasm, mucosal edema or inflammation and ureteral anatomy are the factors affecting passage of the ureteral stones. So, MET is based on mechanism that stone passage is facilitated by the relaxation of ureteral smooth muscle , increasing hydrostatic pressure proximal to the stone and decreasing exciting edema . There are many oral medication could be used as MET such as adrenergic blockers, calcium channel blockers, prostaglandin synthesis inhibitors, glyceryl trinitrate and steroid treatment . Calcium-channel blockers and adrenergic α-antagonists are the main that has been proposed to enhance stone passage as expulsive medical therapy. Cyclic nucleotides are degraded by phosphodiesterases enzymes (PDEs). So using of PDE inhibtors may play role in relaxation of smooth muscle of the ureter. A study was done for evaluation of three PDE5 inhibtors, sildenafil , vardenafil and tadalafil, they found that PDE5 inhibitors can reverse the tension of isolated human ureteral smooth muscle via cGMP-mediated pathways.

Study Overview

• Status: Unknown
• Conditions: Urolithiasis; Ureteral Stone
• Intervention / Treatment: Drug: Sildenafil

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male Patient aged from 18-65 years.
2. Lower third ureteric stones at or below sacro-iliac joint .
3. Stone size rang from 5- 10 mm.
4. Unilateral ureteric stone

Exclusion Criteria:

1. Patients who had recurrent fever.
2. Patient underwent ESWL.
3. Patient with rising serum creatinine > 2mg/dl.
4. Patient with history of uretero-vesical reimplantation.
5. Stone larger than 10 mm

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control; patient receive placebo for 4 weeks and followed for passage of stone distal ureter	Drug: Sildenafil; placebo will take nitrofuratoin once daily for 4 weeks . sildenafil arm will take sildenafil 50 mg once daily for 4 weeks
Active Comparator: sildenafil; patient receive sildenafil 50 mg for 4 weeks once per day and followed for passage of stone distal ureter	Drug: Sildenafil; placebo will take nitrofuratoin once daily for 4 weeks . sildenafil arm will take sildenafil 50 mg once daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the percentage of passage of lower ureteric stones.	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
number of patient need for analgesic treatment during their medical expulsive tharpy	one year

Collaborators and Investigators

• Sponsor: Mansoura University

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): August 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: June 30, 2015
• First Submitted That Met QC Criteria: August 5, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2017
• Last Update Submitted That Met QC Criteria: July 2, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: PDE5i; Phosphodiesterase 5 Inhibitors; Sildinafil
• Additional Relevant MeSH Terms: Urologic Diseases; Pathological Conditions, Anatomical; Ureteral Diseases; Urinary Calculi; Calculi; Urolithiasis; Ureteral Calculi; Ureterolithiasis; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: MThar87