Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder

Abstract

Purpose: We determined the effectiveness of cystoscopic administration of botulinum-A toxin compared to placebo for the treatment of urinary incontinence in subjects with idiopathic overactive bladder.

Materials and methods: Subjects were recruited from the Division of Urogynecology at the University of Rochester. Inclusion criteria were overactive bladder refractory to anticholinergic medications, multiple daily incontinence episodes and a 24-hour pad weight of 100 gm or greater. Subjects with low leak point pressures, increased post-void residual volume or neurological etiologies were excluded from study. Subjects were randomized to placebo or to 1 of 2 doses of botulinum-A toxin. The detrusor was injected at 8 to 10 sites above the trigone. Evaluations were performed at baseline, and at 3 and 6 weeks after injection, and included bladder diaries, pad weights, quality of life questionnaires and urodynamic studies.

Results: A total of 22 subjects participated in stage 1 of this 2-stage study. We report on the outcomes of stage 1 of this study. Because stage 2 is still ongoing and investigators remain blind to the doses of botulinum-A toxin, the 2 botulinum-A toxin groups were combined for this report. There were no differences in mean baseline measurements between the 2 groups. Statistically significant improvements in daily incontinence episodes, pads changed per day and quality of life questionnaires were seen in the botulinum-A toxin group with no changes in the placebo group. No change in nocturia, daily voiding frequency, peak flow or detrusor pressure was seen in either group. Of 15 subjects 4 (26%) receiving botulinum-A toxin had a post-void residual volume of 200 cc or greater and 1 subject required intermittent catheterization. Four subjects experienced a urinary tract infection, 2 (13%) in the botulinum-A toxin group and 2 (28%) in the placebo group (not significant).

Conclusions: Botulinum-A toxin can significantly reduce urge urinary incontinence due to overactive bladder at 6 weeks. However, there is a risk of urinary retention requiring self-catheterization.

Figure 1

Two-stage study design

Figure 2

CONSORT flow diagram of enrollment and study period. Botox, BTX.

Figure 3

BTX vs placebo over time for primary and secondary outcomes