CaOx Stone Prevention

Empiric vs Selective Medical Therapy for Calcium Oxalate Stone Prevention: A Randomized Controlled Trial

This single-center randomized controlled trial at Mount Sinai West will enroll 80 patients undergoing percutaneous nephrolithotomy for calcium oxalate stones. Participants will be randomized to receive either empiric therapy or selective therapy guided by 24-hour urine evaluation. The primary outcome is change in calcium oxalate supersaturation at 4 weeks, aiming to determine whether empiric therapy can provide outcomes comparable to selective therapy while simplifying access to prevention.

Study Overview

• Status: Recruiting
• Conditions: Kidney Stones
• Intervention / Treatment: Drug: Chlorthalidone; Behavioral: Low oxalate diet

Detailed Description

This is a single-center, randomized controlled trial evaluating the effectiveness of empiric versus selective medical therapy for the prevention of calcium oxalate kidney stones. The study will enroll 80 patients at Mount Sinai West undergoing percutaneous nephrolithotomy (PCNL) for predominantly calcium oxalate stones. Participants will be randomized postoperatively to receive either empiric therapy (based on stone composition and urinalysis) or selective therapy (based on 24-hour urine metabolic evaluation). The primary endpoint is the change in calcium oxalate supersaturation (ssCaOx) at 4 weeks post-treatment. The study is designed to determine whether an empiric approach can achieve comparable outcomes to selective therapy while simplifying access to preventive treatment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mantu Gupta, MD; Phone Number: 212-241-1272; Email: Mantu.gupta@mountsinai.org
• Study Contact Backup: Name: Blair Gallante, MPH; Phone Number: 631-991-1159; Email: blair.gallante@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Recruiting
      • Mount Sinai West
      • Contact: Mantu Gupta, MD; Phone Number: 212-241-1272; Email: Mantu.gupta@mountsinai.org
      • Principal Investigator: Mantu Gupta
      • Contact: Blair Gallante, MPH; Phone Number: 631-991-1159; Email: blair.gallante@mountsinai.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult age of 18 years
• Diagnosed with kidney stones and scheduled for PCNL.
• Calcium Oxalate Stone Former
• Pre-operative CT-scan within 90 days of surgery and stone density with > 1000 Hounsfield units
• Non-pregnant or breastfeeding
• Able and willing to provide informed consent.
• Pre-operative eGFR greater than 70 mL/min/1.73 m² -Negative pre-operative urine culture

Exclusion Criteria:

• Documented history of gastric or intestinal bypass, liver disease, history of gastrointestinal malabsorptive disease (Crohn's disease, ulcerative colitis, and short-gut syndrome)
• Hyperparathyroidism -Renal tubular acidosis
• Active kidney stone prevention treatment (use of thiazides, alkaline therapy, or low oxalate diet) at the time of surgery
• History of hypokalemia or baseline hypotension
• Allergy to medications used in trial or sulfa-containing medications
• Patient prescribed thiazide, loop diuretics, carbonic anhydrase inhibitors, xanthine oxidase inhibitors, active Vitamin D, bisphosphonates, denosumab, glucocorticoids, or potassium supplementation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empiric Therapy; Patients randomized to the empiric group will receive treatment based on the pH on urinalysis and stone composition. Patients with greater than 50% calcium oxalate monohydrate (COM) stone composition will be counseled on a low oxalate diet by a medical provider. Patients with greater than 50% calcium oxalate dihydrate (COD) stone composition will be prescribed 25 mg of chlorthalidone once a day. In the rare event the stone composition is 50% COM and 50% COD, then those patients will receive both low oxalate diet counseling and a prescription for chlorthalidone.	Drug: Chlorthalidone; Chlorthalidone 25 mg orally once daily is used to reduce urinary calcium excretion and prevent recurrent calcium-containing kidney stones. In this study, it is prescribed either based on stone composition (empiric group) or guided by 24-hour urine results (selective group) for participants meeting criteria for hypercalciuria or calcium oxalate dihydrate stones.; Behavioral: Low oxalate diet; Participants receive counseling to follow a low oxalate diet, limiting high oxalate foods (>50 mg/100 g) and restricting moderate oxalate foods (<50 mg/100 g) to a single four-ounce serving per day. The diet is prescribed either based on stone composition (empiric group) or guided by 24-hour urine results (selective group) for participants with idiopathic hyperoxaluria or calcium oxalate monohydrate stones.
Active Comparator: Selective Therapy; Patients randomized to the selective group will undergo medical therapy based on the American Urological Association (AUA) guidelines from the 24-hour urine collection results. Patients with idiopathic hyperoxaluria (> 40mg/day) will receive a low oxalate diet and receive the same dietary counseling, handout, and questionnaire as the empiric group. Patients with idiopathic hypercalciuria (> 250mg in men, >200mg in women) will be prescribed 25mg of chlorthalidone once a day.	Drug: Chlorthalidone; Chlorthalidone 25 mg orally once daily is used to reduce urinary calcium excretion and prevent recurrent calcium-containing kidney stones. In this study, it is prescribed either based on stone composition (empiric group) or guided by 24-hour urine results (selective group) for participants meeting criteria for hypercalciuria or calcium oxalate dihydrate stones.; Behavioral: Low oxalate diet; Participants receive counseling to follow a low oxalate diet, limiting high oxalate foods (>50 mg/100 g) and restricting moderate oxalate foods (<50 mg/100 g) to a single four-ounce serving per day. The diet is prescribed either based on stone composition (empiric group) or guided by 24-hour urine results (selective group) for participants with idiopathic hyperoxaluria or calcium oxalate monohydrate stones.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in super saturation of calcium oxalate	Change in urine calcium oxalate supersaturation from baseline to the final follow-up visit, measured via 24-hour urine collection. This is a marker that can be predictive of stone episodes, as recurrent stones may take years to develop.	4-6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in urinary oxalate levels	Difference in 24-hour urinary oxalate excretion from baseline to the final follow-up visit, measured in mg/day, to assess the effect of dietary and pharmacologic interventions on oxalate levels.	4-6 weeks
Changes in urinary calcium levels	Difference in 24-hour urinary calcium excretion from baseline to the final follow-up visit, measured in mg/day, to evaluate the effect of chlorthalidone and dietary interventions on urinary calcium levels.	4-6 weeks
Chlorthalidone Adherence Survey (adapted from Brief Medication Questionnaire)	Participant-reported adherence to prescribed chlorthalidone therapy, assessed via a structured survey at the follow-up visit, to evaluate compliance with the study intervention. Response will be either 0=nonadherent or 1=adherent.	4-6 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Mantu Gupta, MD, Mount Sinai West

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 5, 2025
• First Submitted That Met QC Criteria: November 5, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: kidney stones; nephrolithiasis; calcium oxalate
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urolithiasis; Urinary Calculi; Pathological Conditions, Signs and Symptoms; Kidney Calculi; Nephrolithiasis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Phthalimides; Isoindoles; Benzenesulfonamides; Sulfonamides; Sulfones; Ketones; Benzophenones; Imides; Chlorthalidone
• Other Study ID Numbers: STUDY-25-00784

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because all results are part of standard clinical care, and participants have access to their own medical records.

Drug and device information, study documents

• 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.: No