Treatment for common urinary ailment no longer carved in stone

Newly published results from a large clinical trial indicate that a drug frequently used in the emergency room to treat people with urinary stone disease has no benefit if the stones are below a certain size. Urinary stones, also called kidney stones, are pebble-like masses that can form in the kidneys if there is an excess of certain minerals in the urine. Stones vary in size from a grain of sand to (rarely) a golf ball. Those that get lodged in the ureters—the tubes that carry urine from the kidneys to the bladder—cause extremely painful symptoms. Although many symptom-causing stones subsequently pass out of the body on their own, appropriate medical evaluation is important because, if they do not, they can lead to infection and loss of kidney function. Men are much more prone to stones than women, although recent research suggests that rates may be rising in women. People with symptomatic urinary stones are often first seen in emergency departments. Under current guidelines, if a special imaging technique reveals a stone up to a certain size trapped in a person’s ureter, a recommended first line of treatment is to prescribe a type of drug thought to promote stone expulsion, called an alpha adrenergic receptor blocker, or alpha blocker. One such drug is tamsulosin. The drug is taken by mouth for about a month, along with medication to alleviate pain until the stone passes.

However, because recent studies have called into question whether alpha blockers actually promote passage of stones that are below a certain size (including stones commonly considered large), NIDDK initiated the Study of Tamsulosin for Urolithiasis in the ER (STONE) clinical trial. The goal of the trial was to determine whether symptomatic patients given tamsulosin actually passed a symptomatic stone at a significantly higher rate over the course of 28 days than patients given placebo (no medication) pills. Conducted at six different emergency departments, the STONE trial enrolled 512 participants 18 years of age or older with a symptom-causing stone of less than 9 millimeters (i.e., up to the size of large green pea); the average size was close to 4 millimeters, and over half of the symptom-causing stones fell within the 3 to 4 millimeter range. About three quarters of participants were men. Participants were randomly assigned to either tamsulosin or an identical looking placebo pill to be taken once a day, and then contacted by phone multiple times during the treatment phase to find out whether the stone had passed—i.e., whether he or she had seen or even collected it after urination. The STONE researchers found that, among the 497 persons for whom they had data, 49.6 percent of those in the tamsulosin group and 47.3 percent in the placebo group reported stone passage at 28 days—this small difference was not statistically significant (i.e., it likely happened by chance). Further, while the researchers also did not find significant differences between the groups in factors such as pain medication usage, time away from work, or return ER visits due to a stone, they did find that men on tamsulosin were more likely than men on placebo to report problems with ejaculation (a side effect of tamsulosin that has been noted in the past). These findings, in combination with similar findings from two other trials conducted in the United Kingdom and Australia, indicate no benefit of tamsulosin for promoting passage of stones of the sizes tested and suggest that guidelines for ER treatment of urinary stone disease may need to be revised.

References