Phase IIb/III Dose Ranging Study of Tamsulosin as Treatment for Children With Neuropathic Bladder
We evaluated the efficacy and safety of tamsulosin hydrochloride in children with increased detrusor leak point pressure associated with neuropathic bladder.Materials and Methods
In a double-blind, randomized, placebo controlled trial patients with detrusor leak point pressure 40 cm H2O or greater were stratified by age (2 to less than 5 years, 5 to less than 10 years, 10 to 16 years) and concomitant anticholinergic use, and were randomized to receive various doses of tamsulosin or placebo. A 2-week titration was followed by a 12-week maintenance treatment period. Primary end point was response, ie detrusor leak point pressure less than 40 cm H2O from 2 evaluations on the same day at week 14. Secondary end points included detrusor leak point pressure change from baseline, hydronephrosis and hydroureter responses, change in catheterization volumes and adverse events.Results
A total of 161 patients received 1 or more treatment doses between January 2008 and February 2009, and 135 were evaluable for the primary end point. A total of 51 patients (37.8%) were detrusor leak point pressure responders, with no statistically significant difference in response rates between each tamsulosin dose and placebo. Adjusting for stratification variables, mean detrusor leak point pressure changes from baseline to week 14 for placebo and low, medium and high dose groups were –11.4, –17.6, –4.6 and –14.3 cm H2O, respectively. In 141 evaluable patients hydroureter/hydronephrosis improvement rates were 7.1% and 5.7% in left and right kidneys (hydroureter), respectively, and 14.9% and 14.2% in left and right kidneys (hydronephrosis), respectively. No group experienced decreases in median post-void residual volume at week 14. Drug related adverse event incidences were 4.9% (placebo) and 5.8% (tamsulosin).Conclusions
Tamsulosin was well tolerated but not efficacious in this pediatric population with neuropathic bladder.