Platinum Priority – Female Urology – Incontinence Editorial by Apostolos Apostolidis on pp. 515–517 of this issue| Volume 62, ISSUE 3, P507-514, September 01, 2012

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

Published:January 06, 2012DOI:



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


      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.


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


      Primary 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 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.


      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.


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        • Abrams P.
        • Cardozo L.
        • Fall M.
        • et al.
        The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.
        Neurourol Urodyn. 2002; 21: 167-178
        • Burgio K.L.
        • Locher J.L.
        • Goode P.S.
        • et al.
        Behavioral vs drug treatment for urge urinary incontinence in older women.
        JAMA. 1998; 280: 1995-2000
        • Kirkali Z.
        • Whitaker R.H.
        The use of oxybutynin in urological practice.
        Int Urol Nephrol. 1987; 19: 385-391
        • Abrams P.
        • Freeman R.M.
        • Anderstrom C.
        • Mattiasson A.
        Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.
        Br J Urol. 1999; 81: 801-810
        • Chapple C.R.
        • Rechberger T.
        • Al-Shukri S.
        • et al.
        Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder.
        BJU Int. 2004; 93: 303-310
        • Herbison P.
        • Hay-Smith J.
        • Ellis G.
        • Moore K.
        Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review.
        BMJ. 2003; 326: 841-844
        • Kelleher C.J.
        • Cardozo L.D.
        • Khullar V.
        • Salvatore S.
        A medium-term analysis of the subjective efficacy of treatment for women with detrusor instability and low bladder compliance.
        Br J Obstet Gynaecol. 1997; 104: 988-993
        • Schurch B.
        • Stöhrer M.
        • Kramer G.
        • Schmid D.M.
        • Gaul G.
        • Hauri D.
        Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results.
        J Urol. 2000; 164: 692-697
        • Schurch B.
        • de Seze M.
        • Denys P.
        • et al.
        Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study.
        J Urol. 2005; 174: 196-200
        • Apostolidis A.
        • Dasgupta P.
        • Denys P.
        • et al.
        Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European Consensus Report.
        Eur Urol. 2009; 55: 100-120
        • Yalcin I.
        • Bump R.C.
        Validation of two global impression questionnaires for incontinence.
        Am J Obstet Gynecol. 2003; 189: 98-101
        • Nixon A.
        • Colman S.
        • Sabounjian L.
        • et al.
        A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials.
        J Urol. 2005; 174: 604-607
        • Reitz A.
        • Stöhrer M.
        • Kramer G.
        • et al.
        European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity.
        Eur Urol. 2004; 45: 510-515
        • Avery K.
        • Donovan J.
        • Peters T.J.
        • Shaw C.
        • Gotoh M.
        • Abrams P.
        ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence.
        Neurourol Urodyn. 2004; 23: 322-330
        • Patrick D.L.
        • Martin M.L.
        • Bushnell D.M.
        • Yalcin I.
        • Wagner T.H.
        • Buesching D.P.
        Quality of life of women with urinary incontinence: further development of the Incontinence Quality of Life Instrument (I-QOL).
        Urology. 1999; 53: 71-76
        • Chapple C.
        • Van Kerrebroeck P.
        • Tubaro A.
        • et al.
        Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.
        Eur Urol. 2007; 52: 1204-1212
        • Chapple C.R.
        • Martinez-Garcia R.
        • Selvaggi L.
        • et al.
        A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial.
        Eur Urol. 2005; 48: 464-470
        • Sahai A.
        • Khan M.S.
        • Dasgupta P.
        Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial.
        J Urol. 2007; 177: 2231-2236
        • Brubaker L.
        • Richter H.E.
        • Visco A.
        • et al.
        Refractory idiopathic urge urinary incontinence and botulinum A injection.
        J Urol. 2008; 180: 217-222
        • Flynn M.K.
        • Amundsen C.L.
        • Perevich M.
        • Liu F.
        • Webster G.D.
        Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder.
        J Urol. 2009; 181: 2608-2615
        • Dmochowski R.
        • Chapple C.
        • Nitti V.W.
        • et al.
        Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial.
        J Urol. 2010; 184: 2416-2422