Botulinum toxin a versus placebo for refractory detrusor overactivity in women: a randomised blinded placebo-controlled trial of 240 women (the RELAX study).

BACKGROUND: Emerging data suggest botulinum toxin is an effective treatment for detrusor overactivity (DO), but large studies confirming efficacy and safety are lacking.

OBJECTIVE: Study the efficacy and safety of onabotulinumtoxinA (onaBoNTA) for the treatment of DO.

DESIGN, SETTING, AND PARTICIPANTS: A double-blind placebo-controlled randomised trial in eight UK urogynaecology centres was conducted between 2006 and 2009. A total of 240 women with refractory DO were randomised to active or placebo treatment and followed up for 6 mo.

INTERVENTION: Treatment consisted of 200 IU onaBoNTA or placebo injected into the bladder wall (20 sites; 10 IU per site in 1ml saline).

MEASUREMENTS: Primary outcome was voiding frequency per 24h at 6 mo. Secondary outcomes included urgency and incontinence episodes and quality-of-life data. Intention-to-treat analysis was used with imputation of missing data.

RESULTS AND LIMITATIONS: A total of 122 women received onaBoNTA and 118 received the placebo. Median (interquartile range) voiding frequency was lower after onaBoNTA compared with placebo (8.3 [6.83-10.0] vs 9.67 [8.37-11.67]; difference: 1.34; 95% confidence interval [CI], 1.00-2.33; p=0.0001). Similar differences were seen in urgency episodes (3.83 [1.17-6.67] vs 6.33 [4.0-8.67]; difference: 2.50; 95% CI, 1.33-3.33; p<0.0001) and leakage episodes (1.67 [0-5.33] vs 6.0 [1.33-8.33]; difference: 4.33; 95% CI, 3.33-5.67; p<0.0001). Continence was more common after botulinum toxin type A (BoNTA; 31% vs 12%; odds ratio [OR]: 3.12; 95% CI, 1.49-6.52; p=0.002). Urinary tract infection (UTI; 31% vs 11%; OR: 3.68; 95% CI, 1.72-8.25; p=0.0003) and voiding difficulty requiring self-catheterisation (16% vs 4%; OR: 4.87; 95% CI, 1.52-20.33; p=0.003) were more common after onaBoNTA.

CONCLUSIONS: This randomised controlled trial of BoNTA for refractory DO, the largest to date, confirms efficacy and safety of the compound. UTI (31%) and self-catheterisation (16%) are common. A third of women achieved continence.

TRIAL REGISTRATION: The study received ethical committee approval from the Scottish Multicentre Research Ethics Committee (reference: 04/MRE10/67). The trial has a EudraCT number (2004-002981-39), a clinical trial authorisation from the UK Medicines and Healthcare Regulatory Agency, and it was registered on Current Controlled Trials (ISRCTN26091555) on May 26, 2005.