Effect of Fesoterodine in Vulnerable Elderly Subjects with Urgency Incontinence: A Double-Blind, Placebo Controlled Trial
Abstract
Purpose:
We evaluated the efficacy and safety of flexible dose fesoterodine in medically complex vulnerable elderly subjects with urgency urinary incontinence.
Materials and Methods:
In this 12-week, randomized, double-blind, flexible dose, placebo controlled trial, subjects were community dwelling men and women 65 years old or older. Subjects had scores of 3 or more on the VES-13 (Vulnerable Elders Survey) and 20 or more on the MMSE (Mini-Mental State Examination), and 2 to 15 urgency urinary incontinence episodes and 8 or more micturitions per 24 hours on 3-day baseline diaries. Subjects randomized to fesoterodine received 4 mg once daily for 4 weeks and could then increase to 8 mg based on discussion with the investigator. Subjects receiving 8 mg could decrease the dose to 4 mg at any time (sham escalation and de-escalation for placebo). The primary outcome measure was change in daily urgency urinary incontinence episodes. Secondary outcomes included changes in other diary variables and patient reported quality of life measures. Safety evaluations included self-reported symptoms and post-void residual volume.
Results:
A total of 562 patients were randomized (mean age 75 years, 50.4% age 75 years or greater). Subjects had high rates of comorbidities, polypharmacy and functional impairment. At week 12 the fesoterodine group had significantly greater improvements in urgency urinary incontinence episodes per 24 hours (–2.84 vs –2.20, p = 0.002) and most other diary variables and quality of life, as well as a higher diary dry rate (50.8% vs 36.0%, p = 0.002). Adverse effects were generally similar to those of younger populations including risk of urinary retention.
Conclusions:
To our knowledge this is the first antimuscarinic study in a community based, significantly older, medically complex elderly population with urgency urinary incontinence. Flexible dose fesoterodine significantly improved urgency urinary incontinence episodes and other outcomes vs placebo, and was generally well tolerated.
References
- 1 : Incontinence in the frail elderly: report from the 4th International Consultation on Incontinence. Neurourol Urodyn2010; 29: 165. Google Scholar
- 2 : Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study. Curr Med Res Opin2007; 23: 2697. Google Scholar
- 3 : Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients. J Am Geriatr Soc2002; 50: 799. Google Scholar
- 4 : Efficacy and tolerability of fesoterodine in older and younger subjects with overactive bladder. Urology2010; 76: 1350. Google Scholar
- 5 : Trospium chloride once-daily extended release is efficacious and tolerated in elderly subjects (aged ≥75 years) with overactive bladder syndrome. BJU Int2011; 107: 612. Google Scholar
- 6 : Impact of solifenacin on quality of life, medical care use, work productivity, and health utility in the elderly: an exploratory subgroup analysis. Am J Geriatr Pharmacother2009; 7: 373. Google Scholar
- 7 : Efficacy and tolerability of solifenacin in patients aged ≥65 years with overactive bladder: post-hoc analysis of 2 open-label studies. Postgrad Med2011; 123: 94. Google Scholar
- 8 : Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. Am J Geriatr Pharmacother2006; 4: 14. Google Scholar
- 9 : Darifenacin treatment of patients >or= 65 years with overactive bladder: results of a randomized, controlled, 12-week trial. Curr Med Res Opin2007; 23: 2347. Google Scholar
- 10 : Tolterodine: a safe and effective treatment for older patients with overactive bladder. J Am Geriatr Soc2001; 49: 700. Google Scholar
- 11 : Flexible-dose fesoterodine in elderly subjects with overactive bladder: results of the randomised, double-blind, placebo-controlled study of fesoterodine in an aging population trial. J Am Geriatr Soc2013; 61: 185. Google Scholar
- 12 : Randomized trial of oxybutynin extended versus immediate release for women aged 65 and older with overactive bladder: lessons learned from conducting a trial. J Obstet Gynaecol Can2007; 29: 726. Google Scholar
- 13 : Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study. BJU Int2007; 99: 836. Google Scholar
- 14 : Habit training and oxybutynin for incontinence in nursing home patients: a placebo-controlled trial. J Am Geriatr Soc1988; 36: 40. Google Scholar
- 15 : Does oxybutynin add to the effectiveness of prompted voiding for urinary incontinence among nursing home residents? A placebo-controlled trial. J Am Geriatr Soc1995; 43: 610. Google Scholar
- 16 : Oxybutynin chloride for geriatric urinary dysfunction: a double-blind placebo-controlled study. Age Ageing1989; 18: 195. Google Scholar
- 17 : Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Age Ageing1995; 24: 287. Google Scholar
- 18 World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. Available at www.wma.net/en/30publications/10policies/b3/. Accessed July 11, 2013. Google Scholar
- 19 International Conference on Harmonisation: Guidelines for good clinical practice. Available at www.ich.org/. Accessed July 11, 2013. Google Scholar
- 20 : The validation of the Patient Perception of Bladder Condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol2006; 49: 1079. Google Scholar
- 21 : The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc2001; 49: 1691. Google Scholar
- 22 : Validation of the urinary sensation scale (USS). Neurourol Urodyn2011; 30: 360. Google Scholar
- 23 : “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res1975; 12: 189. Google Scholar
- 24 : Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the OAB-q. Qual Life Res2002; 11: 563. Google Scholar
- 25 : Development and validation of the Overactive Bladder Satisfaction (OAB-S) Questionnaire. Neurourol Urodyn2008; 27: 179. Google Scholar
- 26 : The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc1991; 39: 142. Google Scholar
- 27 : Assessing depressive symptoms in five psychiatric populations: a validation study. Am J Epidemiol1977; 106: 203. Google Scholar
- 28 : Evaluation of voiding dysfunction and measurement of bladder volume. Rev Urol2004; 6: S32. Google Scholar
- 29 : Fesoterodine in randomised clinical trials: an updated systematic clinical review of efficacy and safety. Int Urogynecol J2012; 23: 1337. Google Scholar
- 30 : Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial. J Urol2001; 165: 1452. Link, Google Scholar
