Variability of post-void residual urine volume and bladder voiding efficiency in patients with underactive bladder.

OBJECTIVES: Post-void residual urine volume (PVR) and bladder voiding efficiency (BVE) are widely used as clinical parameters to evaluate patients with voiding dysfunction. The present study was conducted to assess the variability of PVR and BVE determinations in patients with underactive bladder (UAB). In addition, we focused on the bladder volume prior to voiding (BVvoid ) that may influence PVR and BVE, and investigated a correlation between PVR and BVvoid , and between BVE and BVvoid . METHODS: Ten patients with a symptom complex of UAB, who had PVR of 50 mL or greater, were admitted to hospital during a 24-hour period for the measurement of voided volume (VV) and PVR. PVR was measured by transabdominal ultrasonography. BVE was expressed by a fraction (%) of bladder volume evacuated ([VV/BVvoid ] × 100). RESULTS: Ten patients, five men (mean age of 65.0 years) and five women (mean age of 70.2 years), participated in this study. Regardless of gender, there was a large variation in repeated measurements of PVR in an individual patient. PVR increased with an increase in BVvoid , and there was a significant linear relationship between PVR and BVvoid . BVE was approximately constant after every voiding in each patient, and there was no significant linear relationship between BVE and BVvoid . CONCLUSIONS: Measurement of PVR was unreliable because of wide variation in the same individual. The variation of BVE was much smaller than PVR. BVE would be a reliable parameter with good reproducibility for the assessment of emptying function.

A combined proof of concept and dose finding study with multiple endpoints: A Bayesian adaptive design in chronic prostatitis/chronic pelvic pain syndrome.

There is a need for identifying effective drugs or terminating ineffective drugs as early as possible to optimize efficient and cost effective drug development. The aim of the proposed trial was to simultaneously establish Proof of Concept (PoC) and dose finding (DF) for a new drug with a novel mode of action in a new indication. We simulated and executed an adaptive allocation design to investigate the effects of a drug on male patients suffering from chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This manuscript describes the clinical trial simulations and primary analysis results. A Bayesian adaptive allocation procedure was employed to allocate patients to treatment using a normal dynamic linear model. The study was to stop early for efficacy if the probability of a clinically significant difference between an experimental arm and placebo was at least 90%. The study was to stop for futility if the probability that the maximum effective dose was better than placebo by at least the futility difference was less than 20%. During the execution phase the study was stopped early, that is 32% less than planned maximum sample size, due to futility. The final results confirmed that the predefined stopping rules were met. In conclusion, the simulations showed that, if the drug was effective, this adaptive design could accomplish both the goals of PoC and DF. However, the study stopped early for futility in line with the simulation predictions for stopping. This resulted in the early stopping of a trial recruiting patients on ineffective treatment.

The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry.

AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo. The endpoints were the opening urethral pressure measured in each period at four time points (predose and 2, 5.5, and 9 h after dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24 completed the study. The opening urethral pressure was higher in all measurements with filled bladder compared with empty bladder, and during squeezing compared to the resting condition. All three drugs increased the opening urethral pressure during all four conditions with a ranking of their effect on urethral pressure matching their reported clinical effect (difference vs. placebo at their reported time of peak plasma concentrations [Tmax ] during resting with filled bladder: Midodrine 9.3 cmH2 O [95%CI 3.0, 15.5], Duloxetine 24.2 cmH2 O [95%CI 17.9, 30.5], and Reboxetine 44.9 cmH2 O [95% CI 40.2, 52.8] cmH2 O). CONCLUSIONS: Urethral pressure reflectometry is capable of detecting drug-induced changes in urethral tone in various conditions. The magnitude of drug-induced changes by the test drugs seems to match their clinical profile and differences in mode of action.