Randomized Double-blind Placebo-controlled Trial Assessing the Efficacy of Standard and Low Dose Hydrochlorothiazide Treatment in the Prevention of Recurrent Nephrolithiasis

• Status: Active, not recruiting
• Trial end date: 2021-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The investigators plan to assess the efficacy of standard and low dose HCTZ treatment in the recurrence prevention of calcium-containing kidney stones. More specifically, the investigators aim to assess the dose-response relationship for three different dosages of HCTZ.

Study intervention: HCTZ 12.5 mg, 25 mg or 50 mg once daily per os for 24 or 36 months. In addition, all patients in HCTZ treatment arms will receive state-of-the-art non-pharmacologic recommendations for stone prevention according to current guidelines.

Control intervention: Placebo once daily per os for 24 to 36 months. In addition, all patients in the placebo arm will receive state-of-the-art non-pharmacologic recommendations for stone prevention according to current guidelines.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Inselspital, Berne
• Treatments: Hydrochlorothiazide

Criteria

Inclusion Criteria:

1. Informed Consent as documented by signature

2. Age 18 years or older

3. Recurrent kidney stone disease (≥ 2 stone events within the last 10 years prior to randomization)

4. Any past kidney stone containing 50% or more of calcium oxalate, calcium phosphate or a mixture of both

Exclusion Criteria:

1. Pharmacologic prevention for stone recurrence less than 3 months prior to randomization

2. Patients with secondary causes of recurrent calcareous nephrolithiasis including:

• Severe eating disorders (anorexia or bulimia)

• Chronic inflammatory bowel disease, bariatric surgery, intestinal surgery with malabsorption or chronic diarrheal status

• Sarcoidosis

• Primary hyperparathyroidism

• Complete distal tubular acidosis

• Active malignancy

3. Patients with the following medications:

• Thiazide or loop diuretics

• Carbonic anhydrase inhibitors (including topiramate)

• Xanthine oxidase inhibitors (febuxostat or allopurinol)

• Alkali, including potassium citrate or sodium bicarbonate

• Treatment with 1,25-OH Vitamin D (calcitriol)

• Calcium supplementation

• Bisphosphonates

• Denosumab

• Teriparatide

• Glucocorticoids

4. Obstructive uropathy, if not treated successfully

5. Urinary tract infection, if not treated successfully

6. Chronic kidney disease (defined as CKD-EPI eGFR < 30 mL/min per 1,73 m2 body surface area for more than 3 months)

7. Patients with a kidney transplant

8. > 3 gout arthritis episodes within one year prior to randomisation or gout arthritis requiring uric acid lowering therapy

9. Cystinuria at screening

10. Hypokalemia (blood potassium level < 3 mmol/L) at screening

11. Hyponatremia (blood sodium level < 125 mmol/L) at screening

12. Pregnant and lactating women [pregnancy test to 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)]

13. Previous (within 3 months prior to randomization) or concomitant participation in another interventional clinical trial

14. Inability to understand and follow the protocol

15. Known allergy to the study drug