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.

Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known.

The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) 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). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response.

The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support.

ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.

BMC nephrology. 2018 Dec 10*** epublish ***

Nasser A Dhayat, Nicolas Faller, Olivier Bonny, Nilufar Mohebbi, Alexander Ritter, Lisa Pellegrini, Giulia Bedino, Carlo Schönholzer, Reto M Venzin, Carina Hüsler, Irene Koneth, Rosaria Del Giorno, Luca Gabutti, Patrizia Amico, Michael Mayr, Urs Odermatt, Florian Buchkremer, Thomas Ernandez, Catherine Stoermann-Chopard, Daniel Teta, Felix Rintelen, Marie Roumet, Irina Irincheeva, Sven Trelle, Luca Tamò, Beat Roth, Bruno Vogt, Daniel G Fuster

Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Department of Nephrology, CHUV, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland., Department of Nephrology, University Hospital Zurich, Zürich, Switzerland., Department of Nephrology, Regional Hospital Lugano, Lugano, Switzerland., Department of Nephrology, Cantonal Hospital Chur, Chur, Switzerland., Department of Nephrology and Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Department of Nephrology, Regional Hospital Bellinzona, Bellinzona, Switzerland., Medical Outpatient Department, University Hospital Basel, University of Basel, Basel, Switzerland., Department of Nephrology, Cantonal Hospital Luzern, Luzern, Switzerland., Division of Nephrology, Dialysis and Transplantation, Cantonal Hospital Aarau, Aarau, Switzerland., Department of Nephrology, HUG, University Hospital Geneva, University of Geneva, Geneva, Switzerland., Service de Nephrology, Centre Hospitalier du Valais Romand (CHVR), Sion, Switzerland., Clinical Trials Unit, University of Bern, Bern, Switzerland., Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. .

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