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.