Medical Stone Expulsive Therapy for Acutely Obstructed Ureteric Calculi

Getz Pharma

Status and phase: Enrolling; Phase 4

Conditions: Ureteric Stone of Lower Third of Ureter

Treatments: Drug: Tamsulosin Oral Capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT05977647

GTZ-MSE-001-23

Details and patient eligibility

About

As a first treatment option for small-size ureteric stones, α-blockers are now being used for medical expulsive therapy (MET) instead of invasive procedures. There is high evidence of the therapeutic benefit of α-blockers in the treatment of Distal ureteric stone (DUS); also endorsed by international guidelines.

However, limited data is available worldwide, on the effect of silodosin to treat DUS. A multi-center study is needed to confirm the efficacy and safety of therapy.

Full description

A kidney stone is a crystal formed inside the kidney. It is one of the commonest conditions of kidney disease affecting 12% of the world's population. Out of 12% Ureteric stones, around 20% represent cases of urolithiasis, of which 70% are situated in the lower third of the ureter and are termed as 'Distal Ureteric Stones' (DUS). Kidney stone aggravates the risk of end-stage kidney disease and increases the risk of multiple complications. including chronic kidney disease hypertension, diabetes, and cardiovascular diseases. The commonest type of kidney stone is calcium oxalate, which is present in around 70 to 80% of the total reported cases of kidney stones.

There are multiple approaches to the management of ureteric stones, which has evolved over the last 20 years, specifically due to advancements in technology, use of ureteroscopy and shockwave lithotripsy (SWL) as minimally invasive treatment options. However, these interventions are quite expensive and may lead to multiple complications. According to the complication rate of minimally invasive interventions is 2.5%.

As a first treatment option for small-size ureteric stones, α-blockers are now being used for medical expulsive therapy (MET) instead of invasive procedures. As observed through two meta-analyses there is high evidence of the therapeutic benefit of α-blockers in the treatment of DUS seen to be 52% and 44% higher than those patients who have not received any treatment.

There is an endorsement of the use of a-blockers as a management option for ureteric stones by the American Urology Association (AUA) and the European Association of Urology. The α1A- adrenoceptors have proven to play an important effect in intervening contraction of the human ureter, induced by phenylephrine. Silodosin (selective α1-adrenoceptor blocker) in the human ureter was found more efficacious than Tamsulosin (1D-adrenoceptor blocker) in non-adrenaline-induced contractions.

However, limited data is available worldwide, on the effect of silodosin to treat DUS. To the best of our knowledge, there has been no study done on the use of silodosin as MET for DUS in the context of Pakistan. Therefore, this study will be able to provide meaningful data to find the efficacy and safety of silodosin in comparison to Tamsulosin as MET in ureteric stone.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults male and female aged 18 to 70 years
• Patients who give informed consent
• Stone located in the distal 1/3rd of ureter (Single, unilateral and radiopaque ureteral calculus 5 to 10 mm visible on the CT-KUB± X-ray KUB within the ureter
• Serum creatinine level within the normal range (adult men, 0.74 to 1.35 mg/dL & 0.59 to 1.04 mg/dL)
• Ability to tolerate oral fluids and oral pain medication

Exclusion criteria

• Patients already taking an alpha-adrenergic antagonist medication for 4 weeks
• Evidence of any other renal stone simultaneously present or at any location
• Hydronephrosis Grade 3 (Moderate) & Grade 4 (Severe) Patients with eGFR <60 ml/min/1.73m2
• Signs of infection including temperature >38ºC or Urinalysis with any of the following: Positive Leukocyte Esterase, Positive Nitrates, or White Blood Cell Count >5/hfp in the setting of a positive urine culture (defined as a single isolated bacterial species population of >100,000 CFU)
• Patients with chronic pain already undergoing treatment with narcotic medications or drug abusers
• Pregnant or lactating women
• Patient suffering from urinary tract infection, ureteral surgery, and existing DJ stents.
• Clinical jaundice
• Any forms of anatomical obstructions in the urinary tract
• The previously suffering from postural hypotension
• Any other disease jeopardizing participation in trial and could lead to increase patient health risks
• History of allergic reactions with the study drugs (Silodosin or Tamsulosin)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Tamsulosin

Active Comparator group

Description:

Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on tamsulosin 0.4 mg once daily, therapy will be given for a maximum of 4 weeks.

Treatment:

Drug: Tamsulosin Oral Capsule

Silodosin

Active Comparator group

Description:

Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on Silodosin 8 mg once daily. Therapy will be given for a maximum of 4 weeks.

Treatment:

Drug: Tamsulosin Oral Capsule