RecruitingNCT06111885INDAPACHLORUpdated May 6, 2026

Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention

A Phase 2 interventional study of Indapamide 2.5 MG and Hydrochlorothiazide 50Mg in Kidney Stone, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.

Sponsored by Insel Gruppe AG, University Hospital Bern · Phase 2, Interventional, and Prevention

From the registry’s dates

Started Oct 2024; still recruiting 2 years 1 month later.

Phase: Phase 2
Study type: Interventional
Enrollment: 99
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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 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 studied

Kidney Stone

Browse trials for

Keywords

Nephrolithiasis
Kidney stones
Thiazide
Hydrochlorothiazide
Indapamide
Chlorthalidone

In context

Kidney Calculi

509 studies on the registry are indexed under Kidney Calculi; 146 are open to participants now.

This study's planned enrollment of 99 is above the median of 86 across 391 interventional studies indexed under Kidney Calculi.

Browse Kidney Calculi studies →

Lead sponsor

Insel Gruppe AG, University Hospital Bern is the lead sponsor of 741 studies on the registry; 180 are open to participants now.

Browse Insel Gruppe AG, University Hospital Bern studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Written, .
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.

Exclusion criteria

Exclusion criteria:

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 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 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.
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 , defined as women who are not surgically sterilized/hysterectomized, and/or who are 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.

Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 99 participants (estimated)

Study arms

Active comparator
Indapamide + Hydrochlorothiazide + Chlorthalidone
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg
Active comparator
Hydrochlorothiazide + Chlorthalidone + Indapamide
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg
Active comparator
Chlorthalidone + Indapamide + Hydrochlorothiazide
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg
Active comparator
Hydrochlorothiazide + Indapamide + Chlorthalidone
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg
Active comparator
Indapamide + Chlorthalidone + Hydrochlorothiazide
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg
Active comparator
Chlorthalidone + Hydrochlorothiazide + Indapamide
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.
Drug: Indapamide 2.5 MG · Drug: Hydrochlorothiazide 50Mg · Drug: Chlorthalidone 25mg

Interventions

DrugIndapamide 2.5 MG
1 indapamide 2.5 mg capsule per day for 28 days
DrugHydrochlorothiazide 50Mg
1 hydrochlorothiazide 50 mg capsule per day for 28 days
DrugChlorthalidone 25mg
1 chlorthalidone 25 mg capsule per day for 28 days

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: Calcium phosphate supersaturation will be determined at day 28 of each active treatment phase

Secondary outcomes

Blood sodium level change from baseline
Sodium level measured in mmol/l
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Venous pH change from baseline
Venous pH measured in pH units
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Venous pCO2 change from baseline
Venous pCO2 measured in mmHg
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Urine pH change from baseline
pH measured in pH units
Time frame: Data collected at baseline and at day 28 of each active treatment phase

Other outcomes

Abundance of total sodium/chloride co-transporter (SLC12A3) in urinary extracellular vesicles
Abundance of total sodium/chloride co-transporter (SLC12A3) detected by immunoblotting on urinary extracellular vesicles, normalized to the abundance of the urinary extracellular vesicle protein Alix
Time frame: Data collected at baseline and at day 28 of each active treatment phase
Abundance of phosphorylated sodium/chloride co-transporter (SLC12A3) in urinary extracellular vesicles
Abundance of phosphorylated sodium/chloride co-transporter (SLC12A3) detected by immunoblotting on urinary extracellular vesicles, normalized to the abundance of the urinary extracellular vesicle protein Alix
Time frame: Data collected at baseline and at day 28 of each active treatment phase

Study locations

1 of 1 sites recruiting

Inselspital, Department of Nephrology and Hypertension
Bern, 3010, Switzerland
Recruiting
- Daniel Fuster, MD · Contact · daniel.fuster@insel.ch · +41 (0)31 632 31 44
Recruiting

References and documents

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 ↗

Individual participant data

Plan to share: 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.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Started Oct 2024 (actual). Primary completion is estimated for Jun 2027, 32 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered: Oct 26, 2023
First posted: Nov 1, 2023
StartActual: Oct 1, 2024
Primary completionEst.: Jun 30, 2027
CompletionEst.: Jun 30, 2027
Last update: May 6, 2026

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on May 6, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT06111885
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Responsible party: Sponsor
First posted: Nov 1, 2023
Start date: Oct 1, 2024
Primary completion: Jun 30, 2027 (estimated)
Completion: Jun 30, 2027 (estimated)
Last update: May 6, 2026

Study contacts

Daniel G Fuster, M.D.

Contact

daniel.fuster@insel.ch

+41 (0)31 632 31 44

Daniel G Fuster, M.D.

principal investigator · Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, Bern Switzerland

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Indapamide · Hydrochlorothiazide · Chlorthalidone

Other studies in this condition

Kidney Calculi →

Other studies from this sponsor

Insel Gruppe AG, University Hospital Bern →

Start the discussion