Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention

NCT06111885 | Recruiting Phase 2

• 1 other identifier: INDAPACHLOR Trial
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Stone

Keywords

Nephrolithiasis; Kidney stones; Thiazide; Hydrochlorothiazide; Indapamide; Chlorthalidone

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Calcium phosphate supersaturation will be determined at day 28 of each active treatment phase

Secondary Outcomes (35)

• Blood sodium level change from baseline

  Data collected at baseline and at day 28 of each active treatment phase

• Blood potassium level change from baseline

  Data collected at baseline and at day 28 of each active treatment phase

• Blood chloride level change from baseline

  Data collected at baseline and at day 28 of each active treatment phase

• Blood calcium level change from baseline

  Data collected at baseline and at day 28 of each active treatment phase

• Blood magnesium level change from baseline

  Data collected at baseline and at day 28 of each active treatment phase

Other Outcomes (2)

• Abundance of total sodium/chloride co-transporter (SLC12A3) in urinary extracellular vesicles

  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

  Data collected at baseline and at day 28 of each active treatment phase

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: Indapamide 2.5 MG; Drug: Hydrochlorothiazide 50Mg; Drug: Chlorthalidone 25mg

Interventions

Indapamide 2.5 MG DRUG

1 indapamide 2.5 mg capsule per day for 28 days

Chlorthalidone + Hydrochlorothiazide + Indapamide; Chlorthalidone + Indapamide + Hydrochlorothiazide; Hydrochlorothiazide + Chlorthalidone + Indapamide; Hydrochlorothiazide + Indapamide + Chlorthalidone; Indapamide + Chlorthalidone + Hydrochlorothiazide; Indapamide + Hydrochlorothiazide + Chlorthalidone

Hydrochlorothiazide 50Mg DRUG

1 hydrochlorothiazide 50 mg capsule per day for 28 days

Chlorthalidone + Hydrochlorothiazide + Indapamide; Chlorthalidone + Indapamide + Hydrochlorothiazide; Hydrochlorothiazide + Chlorthalidone + Indapamide; Hydrochlorothiazide + Indapamide + Chlorthalidone; Indapamide + Chlorthalidone + Hydrochlorothiazide; Indapamide + Hydrochlorothiazide + Chlorthalidone

Chlorthalidone 25mg DRUG

1 chlorthalidone 25 mg capsule per day for 28 days

Chlorthalidone + Hydrochlorothiazide + Indapamide; Chlorthalidone + Indapamide + Hydrochlorothiazide; Hydrochlorothiazide + Chlorthalidone + Indapamide; Hydrochlorothiazide + Indapamide + Chlorthalidone; Indapamide + Chlorthalidone + Hydrochlorothiazide; Indapamide + Hydrochlorothiazide + Chlorthalidone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Inselspital, Department of Nephrology and Hypertension

Bern, 3010, Switzerland

RECRUITING

Related Publications (1)

• 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.

  PMID: 40523783 BACKGROUND

MeSH Terms

Conditions

Kidney Calculi; Nephrolithiasis

Interventions

Indapamide; Hydrochlorothiazide; Chlorthalidone

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Thiazides; Benzenesulfonamides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Isoindoles

Study Officials

• Daniel G Fuster, M.D.

  Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, Bern Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel G Fuster, M.D.

CONTACT

+41 (0)31 632 31 44; daniel.fuster@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Indapamide, hydrochlorothiazide and chlorthalidone will be provided in identically looking bottles containing identically looking capsules. All trial personnel that is involved in recruitment and care of patients, trial assessment, monitoring and statistical analyses will be blinded to the assigned trial arm.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: November 1, 2023
• Study Start: October 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)