Empiric Versus Selective Prevention Strategies for Kidney Stone Disease

• ClinicalTrials.gov Identifier: NCT05365477
• Recruitment Status: Recruiting
• First Posted: May 9, 2022
• Last Update Posted: January 26, 2023
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): Ryan Hsi, Vanderbilt University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Kidney Stones; Nephrolithiasis	Behavioral: Empiric Therapy: Diet; Drug: Empiric Therapy: Drug; Behavioral: Selective Therapy: Diet; Drug: Selective Therapy: Drug	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Trial of Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
• Actual Study Start Date: August 4, 2022
• Estimated Primary Completion Date: March 31, 2025
• Estimated Study Completion Date: March 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Empiric Therapy; Diet intervention and drug intervention not based on 24 hour urine results	Behavioral: 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; Drug: Empiric Therapy: Drug; Drug(s): indapamide 1.25mg and potassium citrate 15mEq daily.
Experimental: Selective Therapy; Diet intervention and drug intervention based on 24 hour urine results	Behavioral: 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; Drug: 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

Outcome Measures

Primary Outcome Measures :

1. Calcium oxalate supersaturation [ Time Frame: Baseline compared to two months ]
   Calculated calcium oxalate supersaturation in urine
2. Calcium phosphate supersaturation [ Time Frame: Baseline compared to two months ]
   Calculated calcium phosphate supersaturation in urine

Secondary Outcome Measures :

1. Uric acid supersaturation [ Time Frame: Baseline compared to two months ]
   Calculated uric acid supersaturation in urine
2. 24hr urine parameters [ Time Frame: Baseline compared to two months ]
   Urinary volume, calcium, oxalate, potassium, citrate, pH, uric acid, and sodium

Other Outcome Measures:

1. 24hr urine parameters from baseline to month 1 [ Time Frame: Baseline to 1 month ]
   Calculated urinary supersaturations of calcium oxalate, calclium phosphate, uric acid, and urinary volume, calcium, oxalate, potassium, citrate, pH, uric acid, and sodium
2. 24hr urine parameters from month 1 to month 2 [ Time Frame: 1 month to 2 months ]
   Calculated urinary supersaturations of calcium oxalate, calclium phosphate, uric acid, and urinary volume, calcium, oxalate, potassium, citrate, pH, uric acid, and sodium
3. Kidney stone events [ Time Frame: Baseline to 2 months ]
   Assessment of short term kidney stone events by self report and clinical imaging, if available
4. Adverse events [ Time Frame: Baseline to 2 months ]
   Assessment of adverse events - subjective and new hypokalemia, hyponatremia, hypomagnesemia, gouty arthritis or requiring uric acid lowering therapy, newly developed overt diabetes mellitus, allergic reactions, abnormal heart rate and blood pressure.
5. Diet adherence [ Time Frame: Baseline to 2 months ]
   Food diaries
6. Medication adherence [ Time Frame: Baseline to 2 months ]
   Pill counts

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Ryan Hsi, MD; 615-343-2036; ryan.hsi@vumc.org

Contact: Brianne Duncan, RN; 615-875-2395; brianne.duncan@vumc.org

Locations

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

• Principal Investigator: Ryan Hsi, MD; Vanderbilt University Medical Center

  Study Documents (Full-Text)

Documents provided by Ryan Hsi, Vanderbilt University Medical Center:

Informed Consent Form  [PDF] January 15, 2023

More Information

• Responsible Party: Ryan Hsi, Associate Professor of Urology, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT05365477
• Other Study ID Numbers: 200238
• First Posted: May 9, 2022
• Last Update Posted: January 26, 2023
• Last Verified: January 2023

• 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.: Yes

Keywords provided by Ryan Hsi, Vanderbilt University Medical Center:

Prevention

Additional relevant MeSH terms:

Kidney Calculi; Nephrolithiasis; Calculi; Pathological Conditions, Anatomical; Kidney Diseases; Urologic Diseases; Urolithiasis; Urinary Calculi