Kidney StonesPhase 4NCT05365477
Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
A Phase 4 study testing Empiric Therapy: Diet, Empiric Therapy: Drug and Selective Therapy: Diet in people with Kidney Stones and Nephrolithiasis, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Stones, Nephrolithiasis
- What is being tested?
- Empiric Therapy: Diet, Empiric Therapy: Drug and Selective Therapy: Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2022to 31 Mar 2026
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Two or more symptomatic kidney stone events in the last 5 years
- Adult
Who cannot join
- Medullary sponge kidney or renal tubular acidosis
- Untreated urinary obstruction
- Primary hyperparathyroidism
- Primary hyperoxaluria
- Pregnancy
- Inflammatory bowel disease or bowel resection
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Randomized Trial of Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
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.
Read the 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
- Being tested
- Empiric Therapy: Diet, Empiric Therapy: Drug, Selective Therapy: Diet, Selective Therapy: Drug
- Keywords
- Prevention
- Medical subject headings
- Kidney Calculi, Nephrolithiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empiric Therapy: DietBehavioural
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: DrugDrug
Drug(s): indapamide 1.25mg and potassium citrate 15mEq daily.
Selective Therapy: DietBehavioural
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: DrugDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Empiric Therapy | Active comparator | Diet intervention and drug intervention not based on 24 hour urine results Receives: Behavioral: Empiric Therapy: Diet; Drug: Empiric Therapy: Drug |
| Selective Therapy | Experimental | Diet intervention and drug intervention based on 24 hour urine results Receives: Behavioral: Selective Therapy: Diet; Drug: Selective Therapy: Drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calcium Oxalate Supersaturation
Calcium oxalate supersaturation is calculated using an at-home, 24 hour urine collection. The value is calculated based on the EQUIL 2 equation and describes the likelihood of crystallization of calcium oxalate in solution. The test was performed by Litholink (Labcorp, Itasca, IL). The reference interval is 6.0 to 10.0. Higher number indicates a higher supersaturation value (e.g., increased calcium oxalate stone risk). A lower number indicates a lower supersaturation value (e.g., lower calcium oxalate stone risk). When the concentration of calcium and oxalate ions in the urine exceeds their solubility limit, the urine becomes supersaturated, which can lead to spontaneous precipitation of minerals and the formation of crystal nuclei. The measure is a unitless ratio because it is calculated by dividing the concentration product of calcium and oxalate ions in a fluid by their thermodynamic solubility product constant (both numerator and denominator have the same units).
Measured: Assessed at two months
Calcium Phosphate Supersaturation
Calcium phosphate supersaturation is calculated using an at-home, 24 hour urine collection. The value is calculated based on the EQUIL 2 equation and describes the likelihood of crystallization of calcium phosphate in solution. The test was performed by Litholink (Labcorp, Itasca, IL). The reference interval is 0.5 to 2.0. Higher number indicates a higher supersaturation value (e.g., increased calcium phosphate stone risk). A lower number indicates a lower supersaturation value (e.g., lower calcium phosphate stone risk). When the concentration of calcium and phosphate ions in the urine exceeds their solubility limit, the urine becomes supersaturated, which can lead to spontaneous precipitation of minerals and the formation of crystal nuclei. The measure is a unitless ratio because it is calculated by dividing the concentration product of calcium and phosphate ions in a fluid by their thermodynamic solubility product constant (both numerator and denominator have the same units).
Measured: Assessed at two months
Secondary outcomes (5)
Uric Acid Supersaturation
Uric acid supersaturation is calculated using an at-home, 24 hour urine collection. The value is calculated based on the EQUIL 2 equation and describes the likelihood of crystallization of uric acid in solution. The test was performed by Litholink (Labcorp, Itasca, IL). The reference interval is <1.0. Higher number indicates a higher supersaturation value (e.g., increased uric acid stone risk). When the concentration of uric acid ions in the urine exceeds their solubility limit, especially in the context of urine pH, the urine becomes supersaturated, which can lead to spontaneous precipitation of minerals and the formation of crystal nuclei. The measure is a unitless ratio because it is calculated by dividing the concentration product of calcium and oxalate ions in a fluid by their thermodynamic solubility product constant (both numerator and denominator have the same units).
Measured: Assessed at two months
24hr Urine Parameters
Urinary calcium, oxalate, citrate, uric acid
Measured: Measured at two months
24hr Urine Volume
24hr Urine Volume among participants collected at 2 months.
Measured: Two months
24hr Urine Sodium and Potassium
24hr Urine Sodium and Potassium
Measured: Two months
24hr Urine pH
24hr Urine pH
Measured: Two months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2022
- Study start4 Aug 2022
- Primary completion26 Sep 2025
- Study completion31 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney StonesStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Penson, Vanderbilt University Medical Center
- Investigators
- Ryan Hsi, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05365477
- Sponsor's protocol ID
- 200238
- Status last verified
- Aug 2026
- First submitted
- 4 May 2022
- Last updated
- 5 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Widmer A, Lee A, Koyama T, Goldfarb DS, Hsi RS, Silver HJ. Targeted versus empiric approach for prevention of recurrent kidney stones: Insights on diet therapy from a randomized trial. Clin Nutr. 2026 Aug 11;65:106754. doi: 10.1016/j.clnu.2026.106754. Online ahead of print.
PubMed 42617398
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
- ClinicalTrials.gov ID
- NCT05365477
- Acronym / sponsor ID
- 200238
- Conditions
- Kidney Stones, Nephrolithiasis
- Keywords
- Prevention
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 4 Aug 2022 (actual)
- Primary completion
- 26 Sep 2025 (actual)
- Study completion
- 31 Mar 2026 (actual)
- First posted
- 9 May 2022 (actual)
- Results
- Posted 5 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empiric Therapy | Active comparator | Behavioral: Empiric Therapy: Diet, Drug: Empiric Therapy: DrugDiet intervention and drug intervention not based on 24 hour urine results |
| Selective Therapy | Experimental | Behavioral: Selective Therapy: Diet, Drug: Selective Therapy: DrugDiet intervention and drug intervention based on 24 hour urine results |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Two or more symptomatic kidney stone events in the last 5 years
- Adult
Key exclusion criteria (15 listed)
- Medullary sponge kidney or renal tubular acidosis
- Untreated urinary obstruction
- Primary hyperparathyroidism
- Primary hyperoxaluria
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empiric Therapy: DietDiet: 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 | Behavioural | Empiric Therapy |
| Empiric Therapy: DrugDrug(s): indapamide 1.25mg and potassium citrate 15mEq daily. | Drug | Empiric Therapy |
| Selective Therapy: DietDiet: 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 | Behavioural | Selective Therapy |
| Selective Therapy: DrugDrug(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 | Drug | Selective Therapy |
Primary outcome
Calcium Oxalate Supersaturation
Time frame: Assessed at two months
Calcium oxalate supersaturation is calculated using an at-home, 24 hour urine collection. The value is calculated based on the EQUIL 2 equation and describes the likelihood of crystallization of calcium oxalate in solution. The test was performed by Litholink (Labcorp, Itasca, IL). The reference interval is 6.0 to 10.0. Higher number indicates a higher supersaturation value (e.g., increased calcium oxalate stone risk). A lower number indicates a lower supersaturation value (e.g., lower calcium oxalate stone risk). When the concentration of calcium and oxalate ions in the urine exceeds their solubility limit, the urine becomes supersaturated, which can lead to spontaneous precipitation of minerals and the formation of crystal nuclei. The measure is a unitless ratio because it is calculated by dividing the concentration product of calcium and oxalate ions in a fluid by their thermodynamic solubility product constant (both numerator and denominator have the same units).
Calcium Phosphate Supersaturation
Time frame: Assessed at two months
Calcium phosphate supersaturation is calculated using an at-home, 24 hour urine collection. The value is calculated based on the EQUIL 2 equation and describes the likelihood of crystallization of calcium phosphate in solution. The test was performed by Litholink (Labcorp, Itasca, IL). The reference interval is 0.5 to 2.0. Higher number indicates a higher supersaturation value (e.g., increased calcium phosphate stone risk). A lower number indicates a lower supersaturation value (e.g., lower calcium phosphate stone risk). When the concentration of calcium and phosphate ions in the urine exceeds their solubility limit, the urine becomes supersaturated, which can lead to spontaneous precipitation of minerals and the formation of crystal nuclei. The measure is a unitless ratio because it is calculated by dividing the concentration product of calcium and phosphate ions in a fluid by their thermodynamic solubility product constant (both numerator and denominator have the same units).
5 secondary outcomes
Uric Acid Supersaturation
Time frame: Assessed at two months
24hr Urine Parameters
Time frame: Measured at two months
24hr Urine Volume
Time frame: Two months
24hr Urine Sodium and Potassium
Time frame: Two months
24hr Urine pH
Time frame: Two months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42617398Widmer A, Lee A, Koyama T, Goldfarb DS, Hsi RS, Silver HJ. Targeted versus empiric approach for prevention of recurrent kidney stones: Insights on diet therapy from a randomized trial. Clin Nutr. 2026 Aug 11;65:106754. doi: 10.1016/j.clnu.2026.106754. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Hsi, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empiric Therapy: Diet, Empiric Therapy: Drug and Selective Therapy: Diet in people with Kidney Stones and Nephrolithiasis, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calcium Oxalate Supersaturation (time frame: Assessed at two months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05365477, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.