Empiric Versus Selective Prevention Strategies for Kidney Stone Disease

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05365477

Collaborator

(none)

Enrollment

Location

Arms

31.9

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Aug 4, 2022

Anticipated Primary Completion Date :

Mar 31, 2025

Anticipated Study Completion Date :

Mar 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

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

Calcium oxalate supersaturation [Baseline compared to two months]
Calculated calcium oxalate supersaturation in urine
Calcium phosphate supersaturation [Baseline compared to two months]
Calculated calcium phosphate supersaturation in urine

Secondary Outcome Measures

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

Other Outcome Measures

24hr urine parameters from baseline to month 1 [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
24hr urine parameters from month 1 to month 2 [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
Kidney stone events [Baseline to 2 months]
Assessment of short term kidney stone events by self report and clinical imaging, if available
Adverse events [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.
Diet adherence [Baseline to 2 months]
Food diaries
Medication adherence [Baseline to 2 months]
Pill counts

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	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)

None provided.

More Information

Publications

None provided.

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:

Aug 8, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Ryan Hsi, Associate Professor of Urology, Vanderbilt University Medical Center

Prevention

Additional relevant MeSH terms:

Kidney Calculi

Nephrolithiasis

Study Results

No Results Posted as of Aug 8, 2022