Empiric Versus Selective Prevention Strategies for Kidney Stone Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Trial of Empiric Versus Selective Prevention Strategies for Kidney Stone Disease

Conditions
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Kidney Stones, Nephrolithiasis

Intervention / Treatment
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* Behavioral: Empiric Therapy: Diet
* Drug: Empiric Therapy: Drug
* Behavioral: Selective Therapy: Diet
* Drug: Selective Therapy: Drug


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empiric Therapy<br>Diet intervention and drug intervention not based on 24 hour urine results | Behavioral: Empiric Therapy: Diet<br>* 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<br>Drug: Empiric Therapy: Drug<br>* Drug(s): indapamide 1.25mg and potassium citrate 15mEq daily.<br>|
| Experimental: Selective Therapy<br>Diet intervention and drug intervention based on 24 hour urine results | Behavioral: Selective Therapy: Diet<br>* 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<br>Drug: Selective Therapy: Drug<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcium oxalate supersaturation | Calculated calcium oxalate supersaturation in urine | Baseline compared to two months | 
| Calcium phosphate supersaturation | Calculated calcium phosphate supersaturation in urine | Baseline compared to two months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uric acid supersaturation | Calculated uric acid supersaturation in urine | Baseline compared to two months | 
| 24hr urine parameters | Urinary volume, calcium, oxalate, potassium, citrate, pH, uric acid, and sodium | Baseline compared to two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention