Kidney StonePhase 2INDAPACHLORNCT06111885
Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention
A Phase 2 study testing Indapamide 2.5 MG, Hydrochlorothiazide 50Mg and Chlorthalidone 25mg in people with Kidney Stone, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
The aim of this study is to test the efficacy of the two long-acting thiazide-like diuretics indapamide and chlorthalidone in reducing urine supersaturation for calcium oxalate and calcium phosphate compared to the short-acting thiazide diuretic hydrochlorothiazide for the prevention of calcium-containing kidney… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Stone
- What is being tested?
- Indapamide 2.5 MG, Hydrochlorothiazide 50Mg and Chlorthalidone 25mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Oct 2024to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Written, informed consent.
- Age 18 years or older.
- Recurrent kidney stone disease (≥2 kidney stone episodes in the last 10 years prior to randomisation).
- Past kidney stone containing ≥50 % CaOx, CaP, or a mixture of both.
Who cannot join
- Patients with secondary causes of recurrent calcium kidney stones including severe eating disorders (anorexia or bulimia), chronic bowel disease, intestinal or bariatric surgery, sarcoidosis, primary hyperparathyroidism, chronic urinary tract infection.
- Patients with the following medications: Thiazide or loop diuretics, carbonic anhydrase inhibitors (including topiramate), xanthine oxidase inhibitors, alkali, active vitamin D (calcitriol or similar), calcium supplementation, bisphosphonates, denusomab, teriparatide, sodium-glucose co-transporter 2 (SGLT2) inhibitors, strong CYP3A4 inhibitors or inducers (may affect indapamide metabolism), lithium (To be eligible for study participation, patients taking any of the above listed medications at screening must be willing to discontinue these medications at least 28 days before randomization).
- Patients with chronic kidney disease (defined as CKD-EPI eGFR <30 mL/min).
- Patients with glomerulonephritis.
- Patients with the following biochemical imbalances: severe hypercalcemia (>2.8 mmol/L), therapy-resistant hypokalemia or conditions with increased potassium loss, severe hyponatremia (<130 mmol/L), symptomatic hyperuricemia.
- Patients with hepatic encephalopathy or severe liver insufficiency.
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- Patients with severe cardiac insufficiency.
- Patient with a recent cerebrovascular event.
- Patients with a solid organ transplant.
- Pregnant and lactating women (A urine pregnancy test must be performed for women of child-bearing potential, defined as women who are not surgically sterilized/hysterectomized, and/or who are postmenopausal for less than 12 months).
- Previous (within 3 months prior to randomization) or concomitant participation in another interventional clinical trial.
- Previous participation in INDAPACHLOR.
- Inability to understand and follow the protocol.
- Allergy to any one of the study drugs.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Inselspital, Department of Nephrology and Hypertension
Bern, 3010
Daniel Fuster, MD, +41 (0)31 632 31 44, daniel.fuster@insel.ch
About this study
Official title: Randomized, Double-blind, Crossover Trial Assessing the Efficacy of Indapamide and Chlorthalidone Compared to Hydrochlorothiazide for the Reduction of Urine Supersaturation for Kidney Stone Prevention
The aim of this study is to test the efficacy of the two long-acting thiazide-like diuretics indapamide and chlorthalidone in reducing urine supersaturation for calcium oxalate and calcium phosphate compared to the short-acting thiazide diuretic hydrochlorothiazide for the prevention of calcium-containing kidney stones.
Read the detailed description
Background and Rationale:
Kidney stones are the most common condition affecting the kidney. Both prevalence and incidence are increasing rapidly, driven by global warming, urbanization, dietary habits and occupational changes. Kidney stones are highly recurrent, associated with increased mortality, significant morbidity and reduced quality of life, and result in enormous health care expenditures. Hence, effective preventive measures are an undisputed medical need. Thiazide and thiazide-like diuretics ("thiazides") have been the cornerstone of pharmacologic recurrence prevention since >50 years. The NOSTONE trial (NCT03057431), the only state-of-the-art trial ever performed for pharmacologic recurrence prevention, recently revealed that the most widely prescribed and best studied thiazide, hydrochlorothiazide, is not effectively preventing kidney stone recurrence. If these results also apply to the two more potent and long-acting thiazide-like diuretics indapamide and chlorthalidone is currently unknown. No head-to-head comparison of different thiazides for prevention of kidney stone recurrence has ever been performed. Thus, the role of thiazides in the prevention of kidney stone recurrence remains unclear. This poses the urgent need for a clinical trial that addresses this critical knowledge gap.
Objective:
The investigators plan to conduct a single-center, prospective, randomized, double-blind, crossover trial (INDAPACHLOR) to assess if indapamide and chlorthalidone are superior to hydrochlorothiazide in reducing urine supersaturations of calcium oxalate and calcium phosphate, the two best validated biochemical indicators of kidney stone recurrence risk.
Methodology:
Patients will be allocated to indapamide 2.5 mg once daily, chlorthalidone 25 mg once daily and hydrochlorothiazide 50 mg once daily in a random sequence. The three consecutive active treatment periods of 4 weeks each will be separated by wash-out periods of 4 weeks. The investigators will include 99 adult (>18 years old) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium-containing kidney stones (containing ≥ 50% of calcium oxalate, calcium phosphate or a mixture of both). All patients will receive a state-of-the art concomitant non-pharmacologic intervention to prevent stone recurrence according to current guidelines. The primary outcome will be reduction of urine supersaturations of calcium oxalate and calcium phosphate at 4 weeks with indapamide or chlorthalidone compared to hydrochlorothiazide. Secondary outcomes will be changes in 24-hour urine and blood parameters, ambulatory blood pressure and adverse events elicited by indapamide or chlorthalidone compared to hydrochlorothiazide. In an exploratory outcome, the abundance of the thiazide target, the sodium/chloride co-transporter, will be analyzed in urinary extracellular vesicles at 4 weeks.
Expected significance:
INDAPACHLOR will provide long-sought evidence on the comparative efficacy of commonly used thiazides in lowering urine supersaturations and is thus expected to have a strong guideline-changing impact, which will transform patient care for this very common disease.
- Conditions
- Kidney Stone
- Being tested
- Indapamide 2.5 MG, Hydrochlorothiazide 50Mg, Chlorthalidone 25mg
- Keywords
- Nephrolithiasis, Kidney stones, Thiazide, Hydrochlorothiazide, Indapamide, Chlorthalidone
- 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.
Indapamide 2.5 MGDrug
1 indapamide 2.5 mg capsule per day for 28 days
Hydrochlorothiazide 50MgDrug
1 hydrochlorothiazide 50 mg capsule per day for 28 days
Chlorthalidone 25mgDrug
1 chlorthalidone 25 mg capsule per day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Indapamide + Hydrochlorothiazide + Chlorthalidone | Active comparator | 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
| Hydrochlorothiazide + Chlorthalidone + Indapamide | Active comparator | 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
| Chlorthalidone + Indapamide + Hydrochlorothiazide | Active comparator | 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
| Hydrochlorothiazide + Indapamide + Chlorthalidone | Active comparator | 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
| Indapamide + Chlorthalidone + Hydrochlorothiazide | Active comparator | 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
| Chlorthalidone + Hydrochlorothiazide + Indapamide | Active comparator | 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days. Receives: Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome component 1 - calcium oxalate supersaturation in urine
The trial has two primary outcomes that will be assessed separately.
Change from baseline urine calcium oxalate supersaturation to end of treatment.
Calcium oxalate supersaturation will be calculated by the Equil2 program.
Measured: Calcium oxalate supersaturation will be determined at day 28 of each active treatment phase
Primary outcome component 2 - calcium phosphate supersaturation in urine
The trial has two primary outcomes that will be assessed separately.
Change from baseline urine calcium phosphate supersaturation to end of treatment.
Calcium phosphate supersaturation will be calculated by the Equil2 program.
Measured: Calcium phosphate supersaturation will be determined at day 28 of each active treatment phase
Secondary outcomes (35)
Blood sodium level change from baseline
Sodium level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood potassium level change from baseline
Potassium level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood chloride level change from baseline
Chloride level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood calcium level change from baseline
Calcium level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood magnesium level change from baseline
Magnesium level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood phosphate level change from baseline
Phosphate level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Venous bicarbonate level change from baseline
Venous bicarbonate level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Venous pH change from baseline
Venous pH measured in pH units
Measured: Data collected at baseline and at day 28 of each active treatment phase
Venous pCO2 change from baseline
Venous pCO2 measured in mmHg
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood glucose level change from baseline
Glucose level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood creatinine level change from baseline
Creatinine level measured in μmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood urea level change from baseline
Urea level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood uric acid level change from baseline
Uric acid level measured in μmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood albumin level change from baseline
Albumin level measured in g/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood total cholesterol level change from baseline
Total cholesterol level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood HDL cholesterol level change from baseline
HDL cholesterol level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood LDL cholesterol level change from baseline
LDL cholesterol level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood triglyceride level change from baseline
Triglycerides level measured in mmol/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Blood haemoglobin A1c level change from baseline
Haemoglobin A1c activity level measured in mU/l
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine sodium excretion change from baseline
Urine sodium excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine potassium excretion change from baseline
Urine potassium excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine chloride excretion change from baseline
Urine chloride excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine calcium excretion change from baseline
Urine calcium excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine phosphate excretion change from baseline
Urine phosphate excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine magnesium excretion change from baseline
Urine magnesium excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine urea excretion change from baseline
Urine urea excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine creatinine excretion change from baseline
Urine creatinine excretion measured in μmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine uric acid excretion change from baseline
Urine uric acid excretion measured in μmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine citrate excretion change from baseline
Urine citrate excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine sulfate excretion change from baseline
Urine sulfate excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine oxalate excretion change from baseline
Urine oxalate excretion measured in μmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine ammonium excretion change from baseline
Urine ammonium excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine bicarbonate excretion change from baseline
Urine bicarbonate excretion measured in mmol/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine titratable acidity excretion change from baseline
Urine titratable acidity excretion measured in mEq/24 h
Measured: Data collected at baseline and at day 28 of each active treatment phase
Urine pH change from baseline
pH measured in pH units
Measured: Data collected at baseline and at day 28 of each active treatment phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2023
- Study start1 Oct 2024
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney StoneStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Eligible individuals will be randomly allocated to one of six treatment sequences with indapamide 2.5 mg, chlorthalidone 25 mg or hydrochlorothiazide 50 mg once daily per os in the morning. Active treatment phases will be 28 days each, separated by wash out periods of 28 days. Active treatment periods can be extended by a maximum of one week, wash out periods can be extended to a maximum of eight weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel G Fuster, M.D., Principal investigator, Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, Bern Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06111885
- Sponsor's protocol ID
- INDAPACHLOR Trial
- Acronym
- INDAPACHLOR
- Status last verified
- Apr 2026
- First submitted
- 26 Oct 2023
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Once results have been published, trial data will be accessible to external researchers and coded datasets corresponding to each publication will be made available. Investigators wishing to replicate the analyses or to do an individual patient meta-analysis may request the data to the Sponsor-Investigator.
Publications
Scoglio M, Bargagli M, Rintelen F, Roumet M, Trelle S, Fuster DG. Indapamide or chlorthalidone to reduce urine supersaturation for secondary prevention of kidney stones: protocol for a randomised, double-blind, cross-over trial (INDAPACHLOR). BMJ Open. 2025 Jun 16;15(6):e101594. doi: 10.1136/bmjopen-2025-101594.
PubMed 40523783
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Crossover Trial Assessing the Efficacy of Indapamide and Chlorthalidone Compared to Hydrochlorothiazide for the Reduction of Urine Supersaturation for Kidney Stone Prevention
- ClinicalTrials.gov ID
- NCT06111885
- Acronym / sponsor ID
- INDAPACHLOR / INDAPACHLOR Trial
- Conditions
- Kidney Stone
- Keywords
- Nephrolithiasis, Kidney stones, Thiazide, Hydrochlorothiazide, Indapamide, Chlorthalidone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 1 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to test the efficacy of the two long-acting thiazide-like diuretics indapamide and chlorthalidone in reducing urine supersaturation for calcium oxalate and calcium phosphate compared to the short-acting thiazide diuretic hydrochlorothiazide for the prevention of calcium-containing kidney stones.
Detailed description
Background and Rationale:
Kidney stones are the most common condition affecting the kidney. Both prevalence and incidence are increasing rapidly, driven by global warming, urbanization, dietary habits and occupational changes. Kidney stones are highly recurrent, associated with increased mortality, significant morbidity and reduced quality of life, and result in enormous health care expenditures. Hence, effective preventive measures are an undisputed medical need. Thiazide and thiazide-like diuretics ("thiazides") have been the cornerstone of pharmacologic recurrence prevention since >50 years. The NOSTONE trial (NCT03057431), the only state-of-the-art trial ever performed for pharmacologic recurrence prevention, recently revealed that the most widely prescribed and best studied thiazide, hydrochlorothiazide, is not effectively preventing kidney stone recurrence. If these results also apply to the two more potent and long-acting thiazide-like diuretics indapamide and chlorthalidone is currently unknown. No head-to-head comparison of different thiazides for prevention of kidney stone recurrence has ever been performed. Thus, the role of thiazides in the prevention of kidney stone recurrence remains unclear. This poses the urgent need for a clinical trial that addresses this critical knowledge gap.
Objective:
The investigators plan to conduct a single-center, prospective, randomized, double-blind, crossover trial (INDAPACHLOR) to assess if indapamide and chlorthalidone are superior to hydrochlorothiazide in reducing urine supersaturations of calcium oxalate and calcium phosphate, the two best validated biochemical indicators of kidney stone recurrence risk.
Methodology:
Patients will be allocated to indapamide 2.5 mg once daily, chlorthalidone 25 mg once daily and hydrochlorothiazide 50 mg once daily in a random sequence. The three consecutive active treatment periods of 4 weeks each will be separated by wash-out periods of 4 weeks. The investigators will include 99 adult (>18 years old) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium-containing kidney stones (containing ≥ 50% of calcium oxalate, calcium phosphate or a mixture of both). All patients will receive a state-of-the art concomitant non-pharmacologic intervention to prevent stone recurrence according to current guidelines. The primary outcome will be reduction of urine supersaturations of calcium oxalate and calcium phosphate at 4 weeks with indapamide or chlorthalidone compared to hydrochlorothiazide. Secondary outcomes will be changes in 24-hour urine and blood parameters, ambulatory blood pressure and adverse events elicited by indapamide or chlorthalidone compared to hydrochlorothiazide. In an exploratory outcome, the abundance of the thiazide target, the sodium/chloride co-transporter, will be analyzed in urinary extracellular vesicles at 4 weeks.
Expected significance:
INDAPACHLOR will provide long-sought evidence on the comparative efficacy of commonly used thiazides in lowering urine supersaturations and is thus expected to have a strong guideline-changing impact, which will transform patient care for this very common disease.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- Eligible individuals will be randomly allocated to one of six treatment sequences with indapamide 2.5 mg, chlorthalidone 25 mg or hydrochlorothiazide 50 mg once daily per os in the morning. Active treatment phases will be 28 days each, separated by wash out periods of 28 days. Active treatment periods can be extended by a maximum of one week, wash out periods can be extended to a maximum of eight weeks.
| Arm | Type | Receives |
|---|---|---|
| Indapamide + Hydrochlorothiazide + Chlorthalidone | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days. |
| Hydrochlorothiazide + Chlorthalidone + Indapamide | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days. |
| Chlorthalidone + Indapamide + Hydrochlorothiazide | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days. |
| Hydrochlorothiazide + Indapamide + Chlorthalidone | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days. |
| Indapamide + Chlorthalidone + Hydrochlorothiazide | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 2.5 mg indapamide per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days. |
| Chlorthalidone + Hydrochlorothiazide + Indapamide | Active comparator | Drug: Indapamide 2.5 MG, Drug: Hydrochlorothiazide 50Mg, Drug: Chlorthalidone 25mg1 capsule containing 25 mg chlorthalidone per day for 28 days, followed by a 28 days wash out phase, followed by a second treatment phase with 1 capsule containing 50 mg hydrochlorothiazide per day for 28 days, followed by a 28 days wash out phase, followed by a third treatment phase with 1 capsule containing 2.5 mg indapamide per day for 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written, informed consent.
- Age 18 years or older.
- Recurrent kidney stone disease (≥2 kidney stone episodes in the last 10 years prior to randomisation).
- Past kidney stone containing ≥50 % CaOx, CaP, or a mixture of both.
Key exclusion criteria (14 listed)
- Patients with secondary causes of recurrent calcium kidney stones including severe eating disorders (anorexia or bulimia), chronic bowel disease, intestinal or bariatric surgery, sarcoidosis, primary hyperparathyroidism, chronic urinary tract infection.
- Patients with the following medications: Thiazide or loop diuretics, carbonic anhydrase inhibitors (including topiramate), xanthine oxidase inhibitors, alkali, active vitamin D (calcitriol or similar), calcium supplementation, bisphosphonates, denusomab, teriparatide, sodium-glucose co-transporter 2 (SGLT2) inhibitors, strong CYP3A4 inhibitors or inducers (may affect indapamide metabolism), lithium (To be eligible for study participation, patients taking any of the above listed medications at screening must be willing to discontinue these medications at least 28 days before randomization).
- Patients with chronic kidney disease (defined as CKD-EPI eGFR <30 mL/min).
- Patients with glomerulonephritis.
- Patients with the following biochemical imbalances: severe hypercalcemia (>2.8 mmol/L), therapy-resistant hypokalemia or conditions with increased potassium loss, severe hyponatremia (<130 mmol/L), symptomatic hyperuricemia.
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 |
|---|---|---|
| Indapamide 2.5 MG1 indapamide 2.5 mg capsule per day for 28 days | Drug | Chlorthalidone + Hydrochlorothiazide + Indapamide, Chlorthalidone + Indapamide + Hydrochlorothiazide, Hydrochlorothiazide + Chlorthalidone + Indapamide, Hydrochlorothiazide + Indapamide + Chlorthalidone, Indapamide + Chlorthalidone + Hydrochlorothiazide, Indapamide + Hydrochlorothiazide + Chlorthalidone |
| Hydrochlorothiazide 50Mg1 hydrochlorothiazide 50 mg capsule per day for 28 days | Drug | Chlorthalidone + Hydrochlorothiazide + Indapamide, Chlorthalidone + Indapamide + Hydrochlorothiazide, Hydrochlorothiazide + Chlorthalidone + Indapamide, Hydrochlorothiazide + Indapamide + Chlorthalidone, Indapamide + Chlorthalidone + Hydrochlorothiazide, Indapamide + Hydrochlorothiazide + Chlorthalidone |
| Chlorthalidone 25mg1 chlorthalidone 25 mg capsule per day for 28 days | Drug | Chlorthalidone + Hydrochlorothiazide + Indapamide, Chlorthalidone + Indapamide + Hydrochlorothiazide, Hydrochlorothiazide + Chlorthalidone + Indapamide, Hydrochlorothiazide + Indapamide + Chlorthalidone, Indapamide + Chlorthalidone + Hydrochlorothiazide, Indapamide + Hydrochlorothiazide + Chlorthalidone |
Primary outcome
Primary outcome component 1 - calcium oxalate supersaturation in urine
Time frame: Calcium oxalate supersaturation will be determined at day 28 of each active treatment phase
The trial has two primary outcomes that will be assessed separately. Change from baseline urine calcium oxalate supersaturation to end of treatment. Calcium oxalate supersaturation will be calculated by the Equil2 program.
Primary outcome component 2 - calcium phosphate supersaturation in urine
Time frame: Calcium phosphate supersaturation will be determined at day 28 of each active treatment phase
The trial has two primary outcomes that will be assessed separately. Change from baseline urine calcium phosphate supersaturation to end of treatment. Calcium phosphate supersaturation will be calculated by the Equil2 program.
35 secondary outcomes
Blood sodium level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood potassium level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood chloride level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood calcium level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood magnesium level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood phosphate level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Venous bicarbonate level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Venous pH change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Venous pCO2 change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood glucose level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood creatinine level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood urea level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood uric acid level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood albumin level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood total cholesterol level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood HDL cholesterol level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood LDL cholesterol level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood triglyceride level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Blood haemoglobin A1c level change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine sodium excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine potassium excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine chloride excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine calcium excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine phosphate excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine magnesium excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine urea excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine creatinine excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine uric acid excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine citrate excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine sulfate excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine oxalate excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine ammonium excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine bicarbonate excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine titratable acidity excretion change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine pH change from baseline
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 40523783Scoglio M, Bargagli M, Rintelen F, Roumet M, Trelle S, Fuster DG. Indapamide or chlorthalidone to reduce urine supersaturation for secondary prevention of kidney stones: protocol for a randomised, double-blind, cross-over trial (INDAPACHLOR). BMJ Open. 2025 Jun 16;15(6):e101594. doi: 10.1136/bmjopen-2025-101594.
- Individual participant dataSharing planned: No. Once results have been published, trial data will be accessible to external researchers and coded datasets corresponding to each publication will be made available. Investigators wishing to replicate the analyses or to do an individual patient meta-analysis may request the data to the Sponsor-Investigator.
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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.
Daniel G Fuster, M.D. principal investigator
Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, Bern Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Indapamide 2.5 MG, Hydrochlorothiazide 50Mg and Chlorthalidone 25mg in people with Kidney Stone, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 4 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 6 May 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 Switzerland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel G Fuster, M.D. (+41 (0)31 632 31 44, daniel.fuster@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome component 1 - calcium oxalate supersaturation in urine (time frame: Calcium oxalate supersaturation will be determined at day 28 of each active treatment phase). 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 NCT06111885, 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 6 May 2026.