Botulinum Toxin A Versus Placebo for Refractory Detrusor Overactivity in Women: A Randomised Blinded Placebo-Controlled Trial of 240 Women (the RELAX Study)

BackgroundEmerging data suggest botulinum toxin is an effective treatment for detrusor overactivity (DO), but large studies confirming efficacy and safety are lacking.ObjectiveStudy the efficacy and safety of onabotulinumtoxinA (onaBoNTA) for the treatment of DO.Design, setting, and participantsA 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.InterventionTreatment consisted of 200 IU onaBoNTA or placebo injected into the bladder wall (20 sites; 10 IU per site in 1 ml saline).MeasurementsPrimary outcome was voiding frequency per 24 h 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 limitationsA 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.ConclusionsThis 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 registrationThe 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.