Phase 3
N=416
Hydrochlorothiazide for Kidney Stone Recurrence Prevention
Nephrolithiasis
Bottom Line
View on ClinicalTrials.gov: NCT03057431 ↗Enrolled (actual)
416
Serious AEs
1.2%
Results posted
Feb 2024
Primary outcome: Primary: Number of Participants With Stone Recurrences — 60; 62; 61; 49 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo oral capsule (Drug); 12.5 mg hydrochlorothiazide (Drug); 25.0 mg hydrochlorothiazide (Drug); 50.0 mg hydrochlorothiazide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Insel Gruppe AG, University Hospital Bern
- Primary completion
- Dec 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Stone Recurrences |
60; 62; 61; 49 | — |
| SECONDARY Number of Symptomatic Stone Recurrences |
35; 40; 43; 28 | — |
| SECONDARY Number of Radiologic Stone Recurrences. |
46; 44; 32; 31 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Informed Consent as documented by signature
- Age 18 years or older
- Recurrent kidney stone disease (≥ 2 stone events within the last 10 years prior to randomization)
- Any past kidney stone containing 50% or more of calcium oxalate, calcium phosphate or a mixture of both
Exclusion Criteria
- Pharmacologic prevention for stone recurrence less than 3 months prior to randomization
- 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
- 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
- Obstructive uropathy, if not treated successfully
- Urinary tract infection, if not treated successfully
- Chronic kidney disease (defined as CKD-EPI eGFR 3 gout arthritis episodes within one year prior to randomisation or gout arthritis requiring uric acid lowering therapy
- Cystinuria at screening
- Hypokalemia (blood potassium level < 3 mmol/L) at screening
- Hyponatremia (blood sodium level < 125 mmol/L) at screening
- 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)]
- Previous (within 3 months prior to randomization) or concomitant participation in another interventional clinical trial
- Inability to understand and follow the protocol
- Known allergy to the study drug
Data sourced from ClinicalTrials.gov (NCT03057431). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.