The Predictors of Successful Oral Dissolution Therapy in Radiolucent Renal Stones; A Prospective Evaluation

The aim of the study is to evaluate the predictors of success of oral dissolution therapy in radiolucent renal stones in a large series of patients from a tertiary referral center in order to define the optimum case scenarios where oral dissolution therapy could be implemented.

Study Overview

• Status: Completed
• Conditions: Urolithiasis; Renal Stones
• Intervention / Treatment: Drug: Oral alkalinization (Potassium citrate, Allopurinol); Behavioral: Life style modification; Dietary supplement: Dietary recommendations (decrease purine rich diet as red meat and fish, increase vegetables)

Detailed Description

Patients with renal stones, seen through the outpatient clinic in the urology department or post primary intervention for renal stones, will be assessed to see if the patient satisfies all inclusion and exclusion criteria. Patients who are meeting these criteria will be asked to participate in this prospective study. If they agree, they will be asked to sign an informed consent.

Baseline patients' assessment will include;

• Full history taking including

  • Previous stone history regarding presentation and management
  • Previous trial oral dissolution therapy for renal stones and their compliance to the treatment
  • Previous GIT surgery
  • History of chronic medical or metabolic illness e.g; DM

• Clinical examination including

  o Body mass index (BMI)

• Laboratory investigations including;

  • Urine analysis (urine PH)
  • 24 hours urine testing for uric acid and citrate
  • Urine culture
  • Serum creatinine
  • Random blood sugar (RBS)
  • Serum uric acid
  • Serum calcium, phosphorus and magnesium.

• Initial radiological evaluation will include

  • Renal ultrasonography (US)
  • Plain X-rays to exclude the presence of calcification in the targeted stone.
  • Non Contrast Computed Tomography (NCCT) on the abdomen and pelvis.
  • MAG3 diuretic renogram

(All NCCT studies will be performed with multislice helical CT scanners, NCCT images will be obtained from above the kidneys through the bladder base. For each renal stone, its location will be recorded, its size will be measured using the largest dimension from length (L), width (W) and height (H) on axial and coronal reformat images. Its mean density will be recorded by measurement using region of interest just smaller than the stone. Associated hydronephrosis proximal to the stone will be also evaluated (Nakada et al 2000).)

Patient will receive the allocated instructions and medications

Patients' follow up (The aim at follow up is to monitor the urinary PH with adjustment of the dose of potassium citrate and also to assess the compliance of the patients regarding the dietary recommendations and the medications)

• After 2 weeks, 4 weeks, 8 weeks and 12 weeks.

  - the most important parameter will be assessed is the urinary PH every two weeks. The target urinary PH should be kept between6.5 to 7.0, the dose of potassium citrate should be adjusted to achieve this value.

• Patients' compliance to medications intake and the instruction of fluid intake and dietary modification.

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • DK
    • Mansoura, DK, Egypt, 35516
      • Urology and nephrology center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients' criteria:

  1. Ability to give informed consent.
  2. Age more than 18 years.
  3. Absence of significant hydronephrosis, serious urinary tract infection, congenital anomalies or distal ureteric obstruction in the affected renal unit.
  4. Normal cardiac, hematological, and renal functions.

• Stone criteria:

  1. Primary or recurrent renal stone.
  2. Patients with residual renal stones after primary intervention whether open surgery, endoscopic or ESWL.
  3. Peripheral calyceal stones or stone in the renal pelvis with no significant hydronephrosis.
  4. Stone size less than 3 cm in maximum diameter
  5. Stones with radiodensity less than 600 Hounsefield units attenuation in Non Contrast Computed Tomography (NCCT).

Exclusion Criteria:

• Patients' criteria:

  1. Inability to give informed consent.
  2. Age less than 18 years
  3. Patients with unremitting pain or serious urinary tract infection.
  4. Presence of significant hydronephrosis, congenital anomalies or distal ureteric obstruction in the affected renal unit.
  5. Abnormal cardiac, hematological or renal functions.

• Stone criteria:

  1. Obstructing stone in the renal pelvis with significant hydronephrosis.

  2. Assumption of presence of calcium stones by presence of calcification in the stone in plain X-rays.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study group; Eligible patients, who fulfilled the study criteria, will be instructed For; Oral alkalinizationPotassium citrate 20 mEq three times dailyHyperuricosuric patients (24-hours urine uric acid more than 750 mg/day in male and more than 650mg/day in females), will receive Allopurinol, a competitive inhibitor of xanthine oxidase, in a dose of 300 mg daily.; Life style modification Adequate fluid intake in order to maintain urine volume between 2-3 L per day.; Dietary recommendations In hyperuricosuric patients (24-hours urine uric acid more than 750 mg/day in male and more than 650mg/day in females) ; - Dietary modification will be advised in the form of decrease purine rich diet as red meat and fish, increase vegetables.

Drug: Oral alkalinization (Potassium citrate, Allopurinol); Eligible patients, who fulfilled the study criteria, will be instructed For; Oral alkalinization therapy; Potassium citrate 20 mEq three times daily; Hyperuricosuric patients (24-hours urine uric acid more than 750 mg/day in male and more than 650mg/day in females) will receive: Allopurinol, a competitive inhibitor of xanthine oxidase, in a dose of 300 mg daily.; Other Names: systemic chemolysis; Behavioral: Life style modification; Eligible patients, who fulfilled the study criteria, will be also instructed for; Adequate fluid intake in order to maintain urine volume between 2-3 L per day.; Dietary supplement: Dietary recommendations (decrease purine rich diet as red meat and fish, increase vegetables); Eligible patients, who fulfilled the study criteria and they are hyperuricosuric (24-hours urine uric acid more than 750 mg/day in male and more than 650mg/day in females) will be also instructed for; Dietary modification will be advised in the form of decrease purine rich diet as red meat and fish, increase vegetables.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint of this study will be change in stone surface area after 3 months of the determined protocol	The stone surface area will be measured using the formula; Surface area = length X width X 0.25 X (22/7) Comparison of the stone surface area in relation to the initial surface area will be done.	participants will be followed for the duration of medical treatment which is specified to be 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the predictors of response (more than 50% reduction in the surface area of the stone) to medical treatment	The percent reduction of stone surface area will be calculated using the formula: Surface area = length X width X 0.25 X (22/7) Categorization of the patients into three groups will be done: Patients who achieved 50% or more reduction in the stone surface area will be considered responsive and would be counseled for another 3 months therapy.; Patients with partial response, less than 50% reduction in stone surface area will be counseled for auxiliary procedure based on stone criteria e.g. ESWL.; Patients with no response/ serious renal infections or serious treatment adverse effects will be considered for other interventional treatment modalities. In the responders groups, factors predicting the success of treatment will be determined	participants will be followed for the duration of medical treatment which is specified to be 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cost efficiency of this procedure	Cumulative cost of medical treatment, including cost of medications and cost savings of sparred medical resources of interventional treatment will be assessed.	participants will be followed for the duration of medical treatment which is specified to be 3 months

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Chair: Ahmed A. Shokeir, MD, Urology And Nephrology Center, Mansoura University, Mansoura

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): February 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Radiolucent renal stones; Oral dissolution therapy; Systemic chemolysis; Renal uric acid stones; Alkalinization
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urinary Calculi; Urolithiasis; Calculi; Kidney Calculi; Nephrolithiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Natriuretic Agents; Diuretics; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Expectorants; Allopurinol; Potassium Citrate
• Other Study ID Numbers: AEl-Sawy122015