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Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention

ConditionKidney Stone
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorInsel Gruppe AG, University Hospital Bern

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Crossover

Treatments tested in this trial

  • Indapamide 2.5 MG

    Drug

    1 indapamide 2.5 mg capsule per day for 28 days

  • Hydrochlorothiazide 50Mg

    Drug

    1 hydrochlorothiazide 50 mg capsule per day for 28 days

  • Chlorthalidone 25mg

    Drug

    1 chlorthalidone 25 mg capsule per day for 28 days

Treatment groups

99 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Indapamide + Hydrochlorothiazide + ChlorthalidoneActive comparator 3 interventions
Group B: Hydrochlorothiazide + Chlorthalidone + IndapamideActive comparator 3 interventions
Group C: Chlorthalidone + Indapamide + HydrochlorothiazideActive comparator 3 interventions
Group D: Hydrochlorothiazide + Indapamide + ChlorthalidoneActive comparator 3 interventions
Group E: Indapamide + Chlorthalidone + HydrochlorothiazideActive comparator 3 interventions
Group F: Chlorthalidone + Hydrochlorothiazide + IndapamideActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

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
2

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

1

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
2

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
3

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
4

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

Other outcomes

1

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
2

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Insel Gruppe AG, University Hospital Bern

Lead sponsor

Source ClinicalTrials.gov
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