Empiric Versus Selective Prevention Strategies for Kidney Stone Disease

NCT ID: NCT05365477

Last Updated: 2025-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-04
• Study Completion Date: 2025-10-17

Brief Summary

The aims of this study are to 1) Conduct a randomized clinical trial of selective versus empiric diet plus pharmacologic therapy in high-risk stone formers and 2) Determine adverse effects from, and adherence to selective and empiric strategies.

Detailed Description

Diet and pharmacologic interventions for preventing future kidney stone episodes are effective, however clinical guideline panels disagree on whether clinicians should perform selective therapy: performing 24-hour urine testing to guide choosing interventions to correct abnormal urinary parameters. The alternative strategy is empiric therapy: applying interventions without 24-hour urine testing. While 24-hour urine testing is considered the standard of care by nephrology and urology specialties for higher risk patients, the American College of Physicians does not recommend 24-hour urine testing.

This is a randomized clinical trial of selective versus empiric therapy for patients with presumed idiopathic calcium stone disease, representing >80% of the kidney stone population. The primary outcome is change in urinary supersaturation, which associates with symptomatic stone recurrence. We will recruit patients with presumed idiopathic calcium stone disease with at least 2 stone events within the previous 5 years. Participants will be randomly assigned to empiric diet plus thiazide with potassium citrate daily, or to selective diet plus pharmacologic therapy based on the 24-hour urine abnormalities identified at baseline and adjusted during follow-up. The primary outcomes will be the calculated calcium oxalate and calcium phosphate supersaturations. In addition, we will determine adverse effects from, and adherence to, selective and empiric strategies.

Conditions

Kidney Stones; Nephrolithiasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Empiric Therapy

Diet intervention and drug intervention not based on 24 hour urine results

Group Type: ACTIVE_COMPARATOR

Empiric Therapy: Diet

Intervention Type: BEHAVIORAL

Diet: High water intake - at least 2.5 liters daily Reduce sugar-sweetened cola intake to ≤3 cans per week. Reduce salt intake to \<2000mg sodium daily Reduce red meat intake to two 4-ounce portions per week Normal calcium intake: 3 servings of dairy products (or their equivalents) per day Increase vegetable and fruit intake to ≥5 servings per day Reduce oxalate intake to \<100 mg/day

Empiric Therapy: Drug

Intervention Type: DRUG

Drug(s): indapamide 1.25mg and potassium citrate 15mEq daily.

Selective Therapy

Diet intervention and drug intervention based on 24 hour urine results

Group Type: EXPERIMENTAL

Selective Therapy: Diet

Intervention Type: BEHAVIORAL

Diet:

Volume <2.5L Increase fluid intake to ≥ 2.5L/d, based on specific urine volume

Calcium >250mg male, >200mg female Reduce red meat intake to two 4-oz portions/wk; reduce sodium intake to<2000mg/d, avoid vitamin D + calcium supplements

Oxalate >40mg Reduce dietary oxalate intake to <100 mg/d; increase fiber intake to 25-35 g/d

Citrate <450mg male, <550mg female Reduce red meat intake to two 4-oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

pH<5.8 Reduce red meat intake to two 4-oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Uric acid >800mg male, >750mg female Reduce red meat intake to two 4- oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Sodium >150mmol Reduce sodium intake to <2000mg/d

Sulfate > 80mEq or urine urea nitrogen >14g Reduce red meat intake to three 3-4 oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Selective Therapy: Drug

Intervention Type: DRUG

Drug(s):

For calcium >250mg male, >200mg female: indapamide 1.25mg and potassium chloride 20mEq. At 1 month if persistent, then increase to indapamide 2.5mg and potassium chloride 20mEq. For citrate <450mg male, <550mg female: potassium citrate 15mEq BID. At 1 month if persistent, then increase to potassium citrate 30mEq BID. For pH<5.8: potassium citrate 15mEq BID. At month if persistent, then increase to potassium citrate 30mEq BID. For uric acid >800mg male, >750mg female: allopurinol 300mg.

If both elevated calcium and low pH: indapamide 1.25mg and potassium citrate 15mEq BID If both elevated calcium and low citrate: indapamide 1.25mg and potassium citrate 15mEq BID

Interventions

Empiric Therapy: Diet

Diet: High water intake - at least 2.5 liters daily Reduce sugar-sweetened cola intake to ≤3 cans per week. Reduce salt intake to \<2000mg sodium daily Reduce red meat intake to two 4-ounce portions per week Normal calcium intake: 3 servings of dairy products (or their equivalents) per day Increase vegetable and fruit intake to ≥5 servings per day Reduce oxalate intake to \<100 mg/day

Intervention Type: BEHAVIORAL

Empiric Therapy: Drug

Drug(s): indapamide 1.25mg and potassium citrate 15mEq daily.

Intervention Type: DRUG

Selective Therapy: Diet

Diet:

Volume <2.5L Increase fluid intake to ≥ 2.5L/d, based on specific urine volume

Calcium >250mg male, >200mg female Reduce red meat intake to two 4-oz portions/wk; reduce sodium intake to<2000mg/d, avoid vitamin D + calcium supplements

Oxalate >40mg Reduce dietary oxalate intake to <100 mg/d; increase fiber intake to 25-35 g/d

Citrate <450mg male, <550mg female Reduce red meat intake to two 4-oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

pH<5.8 Reduce red meat intake to two 4-oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Uric acid >800mg male, >750mg female Reduce red meat intake to two 4- oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Sodium >150mmol Reduce sodium intake to <2000mg/d

Sulfate > 80mEq or urine urea nitrogen >14g Reduce red meat intake to three 3-4 oz portions/wk; increase fruit and vegetable intake to ≥5 svgs/d

Intervention Type: BEHAVIORAL

Selective Therapy: Drug

Drug(s):

For calcium >250mg male, >200mg female: indapamide 1.25mg and potassium chloride 20mEq. At 1 month if persistent, then increase to indapamide 2.5mg and potassium chloride 20mEq. For citrate <450mg male, <550mg female: potassium citrate 15mEq BID. At 1 month if persistent, then increase to potassium citrate 30mEq BID. For pH<5.8: potassium citrate 15mEq BID. At month if persistent, then increase to potassium citrate 30mEq BID. For uric acid >800mg male, >750mg female: allopurinol 300mg.

If both elevated calcium and low pH: indapamide 1.25mg and potassium citrate 15mEq BID If both elevated calcium and low citrate: indapamide 1.25mg and potassium citrate 15mEq BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Two or more symptomatic kidney stone events in the last 5 years
• Adult

Exclusion Criteria

• Medullary sponge kidney or renal tubular acidosis
• Untreated urinary obstruction
• Primary hyperparathyroidism
• Primary hyperoxaluria
• Pregnancy
• Inflammatory bowel disease or bowel resection
• Sarcoidosis
• Cystinuria
• Prior stone composition with uric acid, struvite, cystine, carbonate apatite
• Use of specific medications (thiazides, topiramate, xanthine oxidase inhibitors, citrate, bicarbonate)
• Chronic kidney disease stage 3 or higher (eGFR<60)
• Gouty arthritis or 3 gout episodes in 1 year
• Known allergy to study medications
• Hypokalemia or hyponatremia at screening.
• Age < 18 years

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David Penson

Professor and Chair, Department of Urology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ryan Hsi, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

200238

Identifier Type: -

Identifier Source: org_study_id