NOSTONE Trial: Randomized double-blind placebo-controlled trial assessing the efficacy of standard and low dose hydrochlorothiazide treatment in the prevention of calcareous nephrolithiasis recurrence

Background Nephrolithiasis is a global healthcare problem with a current lifetime risk of up to 18.8% in men and 9.4% in women. Without specific treatment, 5‐ and 20‐year recurrence rates are 40% and 75%, respectively. 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. Nowadays, thiazides are widely used in the treatment of recurrent nephrolithiasis and arterial hypertension. In the case of recurrent nephrolithiasis, however, this practice is not supported by randomized evidence. Thus, evidence for benefits and harms of low dose thiazides in the prevention of calcium‐containing kidney stones in general remains unclear. Methods The NOSTONE clinical trial is a multicenter, randomized, placebo‐controlled, double‐blind, parallel‐group trial to assess the dose‐response relationship for three different dosages of HCTZ (12.5mg, 25.0 mg, 50.0 mg). The primary outcome is the incidence of stone recurrence (a composite of symptomatic and radiologic recurrence); a low‐dose CT will be performed at the beginning and at the end of the trial. The study aims to include 416 patients, recruited from 12 hospitals throughout Switzerland. Results Recruitment started in Bern on March 9th 2017; all study sites are operative since June 30th2017. All sites but Bern closed recruitment on August 31st 2019; Bern continued recruiting until October 31st 2019. The target number of 416 participants randomized in the trial was reached (regular updates: www.nostone.ch). Since March 2020, patients started completing the study according to schedule and the last patient's last visit will take place in August 2021. Conclusions The NOSTONE recruitment target was reached. The trial will end in August 2021, results are expected in early 2022. The NOSTONE study will provide long‐sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones.