Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention

Last updated: February 17, 2025
Sponsor: Insel Gruppe AG, University Hospital Bern
Overall Status: Active - Recruiting

Phase

2

Condition

Kidney Stones

Treatment

Indapamide 2.5 MG

Hydrochlorothiazide 50Mg

Chlorthalidone 25mg

Clinical Study ID

NCT06111885
INDAPACHLOR Trial
  • Ages > 18
  • All Genders

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.

Eligibility Criteria

Inclusion

Inclusion criteria:

  • Written, informed consent.

  • Age 18 years or older.

  • Recurrent kidney stone disease (≥2 kidney stone episodes in the last 10 years priorto randomisation).

  • Past kidney stone containing ≥50 % CaOx, CaP, or a mixture of both.

Exclusion

Exclusion criteria:

  • Patients with secondary causes of recurrent calcium kidney stones including severeeating disorders (anorexia or bulimia), chronic bowel disease, intestinal orbariatric surgery, sarcoidosis, primary hyperparathyroidism, chronic urinary tractinfection.

  • Patients with the following medications: Thiazide or loop diuretics, carbonicanhydrase 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, strongCYP3A4 inhibitors or inducers (may affect indapamide metabolism), lithium (To beeligible for study participation, patients taking any of the above listedmedications 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 (>2.8mmol/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 ofchild-bearing potential, defined as women who are not surgicallysterilized/hysterectomized, and/or who are postmenopausal for less than 12 months).

  • Previous (within 3 months prior to randomization) or concomitant participation inanother interventional clinical trial.

  • Previous participation in INDAPACHLOR.

  • Inability to understand and follow the protocol.

  • Allergy to any one of the study drugs.

Study Design

Total Participants: 99
Treatment Group(s): 3
Primary Treatment: Indapamide 2.5 MG
Phase: 2
Study Start date:
October 01, 2024
Estimated Completion Date:
June 30, 2027

Study 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.

Connect with a study center

  • Inselspital, Department of Nephrology and Hypertension

    Bern, 3010
    Switzerland

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.