Hydrochlorothiazide for Kidney Stone Recurrence Prevention

NCT03057431 | Completed Phase 3 Results

• 1 other identifier: 2016-01475
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Nephrolithiasis

Keywords

kidney stones; hydrochlorothiazide

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Stone Recurrences

  Composite of symptomatic or radiological recurrences, defined as either a symptomatic kidney stone passage or radiological kidney stone recurrence on CT. Symptomatic recurrence was defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal. If a patient had symptoms during the trial that were suggestive of a possible stone passage but no visible stone had been observed, local investigators evaluated the symptoms of the patient and judged whether a stone passage had occurred. Radiological recurrence was defined as a new stone formed or enlargement of a preexisting stone.

  After 3 years

Secondary Outcomes (2)

• Number of Symptomatic Stone Recurrences

  After 3 years

• Number of Radiologic Stone Recurrences.

  After 3 years

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Once daily for 3 years

Drug: Placebo oral capsule

12.5 mg hydrochlorothiazide

EXPERIMENTAL

Once daily for 3 years

Drug: 12.5 mg hydrochlorothiazide

25.0 mg hydrochlorothiazide

EXPERIMENTAL

Once daily for 3 years

Drug: 25.0 mg hydrochlorothiazide

50.0 mg hydrochlorothiazide

EXPERIMENTAL

Once daily for 3 years

Drug: 50.0 mg hydrochlorothiazide

Interventions

Placebo oral capsule DRUG

Once daily for 3 years

Placebo

12.5 mg hydrochlorothiazide DRUG

Once daily for 3 years

12.5 mg hydrochlorothiazide

25.0 mg hydrochlorothiazide DRUG

Once daily for 3 years

25.0 mg hydrochlorothiazide

50.0 mg hydrochlorothiazide DRUG

Once daily for 3 years

50.0 mg hydrochlorothiazide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (12)

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Ospedale Regionale di Bellinzona e Valli (San Giovanni)

Bellinzona, 6500, Switzerland

Location

Bern University Hospital (Inselspital)

Bern, 3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Hôpitaux universitaires de Genève (HUG)

Geneva, 1205, Switzerland

Location

Centre hospitalier universitaire vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Ospedale Regionale di Lugano (Civico)

Lugano, 6900, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Hôpital de Sion

Sion, 1951, Switzerland

Location

University Hospital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (3)

• Dhayat NA, Bonny O, Roth B, Christe A, Ritter A, Mohebbi N, Faller N, Pellegrini L, Bedino G, Venzin RM, Grosse P, Husler C, Koneth I, Bucher C, Del Giorno R, Gabutti L, Mayr M, Odermatt U, Buchkremer F, Ernandez T, Stoermann-Chopard C, Teta D, Vogt B, Roumet M, Tamo L, Cereghetti GM, Trelle S, Fuster DG. Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence. N Engl J Med. 2023 Mar 2;388(9):781-791. doi: 10.1056/NEJMoa2209275.

  PMID: 36856614 RESULT

• Stritt K, Fuster DG, Dhayat NA, Bonny O, Faller N, Christe A, Taha A, Ochs V, Ortlieb N, Roth B; on behalf of the NOSTONE Study. Risk Factors of Asymptomatic Kidney Stone Passage in Adults with Recurrent Kidney Stones. Clin J Am Soc Nephrol. 2024 Sep 1;19(9):1130-1137. doi: 10.2215/CJN.0000000000000496. Epub 2024 Jul 19.

  PMID: 39028573 DERIVED

• Dhayat NA, Faller N, Bonny O, Mohebbi N, Ritter A, Pellegrini L, Bedino G, Schonholzer C, Venzin RM, Husler C, Koneth I, Del Giorno R, Gabutti L, Amico P, Mayr M, Odermatt U, Buchkremer F, Ernandez T, Stoermann-Chopard C, Teta D, Rintelen F, Roumet M, Irincheeva I, Trelle S, Tamo L, Roth B, Vogt B, Fuster DG. Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial. BMC Nephrol. 2018 Dec 10;19(1):349. doi: 10.1186/s12882-018-1144-6.

  PMID: 30526528 DERIVED

MeSH Terms

Conditions

Nephrolithiasis; Kidney Calculi

Interventions

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Limited ethnic diversity, underrepresentation of women, trial duration of 3 years.

Results Point of Contact

• Title: Prof. Daniel Fuster
• Organization: Inselspital, Bern University Hospital, Bern, Switzerland

daniel.fuster@insel.ch

++41316323144

Study Officials

• Daniel Fuster, Prof MD

  Division of Nephrology and Hypertension, Bern University Hospital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 20, 2017
• Study Start: March 9, 2017
• Primary Completion: December 3, 2021
• Study Completion: April 30, 2022
• Last Updated: February 1, 2024
• Results First Posted: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (12)