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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.


Detailed Summary:

Nephrolithiasis is a global healthcare problem with a current lifetime risk of 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.

About 80-90% of stones are composed of calcium oxalate with various admixtures of calcium phosphate. Increased excretion of calcium in the urine, hypercalciuria, is the most common metabolic abnormality encountered in patients with recurrent nephrolithiasis. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. The effect of thiazides to reduce the risk of stone recurrence has been attributed to their ability to decrease urinary calcium excretion. However, other factors, such as reduction of urinary pH and urinary oxalate excretion, probably contribute to this effect. Efficacy of thiazides on recurrence prevention of calcareous nephrolithiasis was tested in 11 randomized controlled trials (RCTs). With the exception of two trials, thiazides significantly reduced stone recurrence. Most of these trials are from the 1980's and 90's and the cumulative number of patients studied is remarkably low for such a prevalent disease. Our systematic review of these RCTs revealed major methodological deficiencies in all trials, including: lack of double-blinding and intention-to-treat analysis, unclear allocation concealment, lack of adverse event and drop out reporting and unknown baseline risk of disease severity. Furthermore, high doses of thiazides were employed in all trials, in the case of the best studied thiazide, hydrochlorothiazide (HCTZ), up to 100 mg daily. At such high doses, side effects occur frequently. Nowadays, thiazides are widely
Sponsor: University Hospital Inselspital, Berne

Current Primary Outcome: Number of stone recurrences [ Time Frame: After 3 years ]

Composite of symptomatic or radiological recurrences


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of symptomatic stone recurrences [ Time Frame: After 3 years ]
  • Number of radiologic stone recurrences [ Time Frame: After 3 years ]
    Measured by low-dose CT


Original Secondary Outcome: Same as current

Information By: University Hospital Inselspital, Berne

Dates:
Date Received: February 15, 2017
Date Started: March 9, 2017
Date Completion: February 28, 2021
Last Updated: May 9, 2017
Last Verified: May 2017