Tags

Type your tag names separated by a space and hit enter

Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial.

Abstract

OBJECTIVE

To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post-baseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes (PROs).

PATIENTS AND METHODS

This was a 12-week, randomised, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with overactive bladder (OAB) symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Patients were randomised (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; those randomised to fesoterodine 8 mg started with fesoterodine 4 mg once daily for 1 week, then 8 mg once daily for the remaining 11 weeks. Patients completed bladder diaries at baseline and weeks 4 and 12 and the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. The primary endpoint was change from baseline to week 12 in UUI episodes per 24 h.

RESULTS

At week 12, patients receiving fesoterodine 8 mg (779 patients) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than patients receiving fesoterodine 4 mg (790) or placebo (386); diary-dry rate was significantly higher in the fesoterodine 8-mg group vs the fesoterodine 4-mg and placebo groups (all P < 0.05). At week 12, patients receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than patients receiving fesoterodine 4 mg or placebo (all P < 0.01). Patients receiving fesoterodine 4 mg had significantly greater improvements in UUI episodes, urgency episodes, and micturitions; significantly higher diary-dry rates; and significantly greater improvement in PPBC scores and OAB-q scores than patients receiving placebo (all P < 0.05). Dry mouth was the most commonly reported adverse event (AE) in the fesoterodine groups (placebo group, 3.4%; fesoterodine 4-mg group, 12.9%; fesoterodine 8-mg group, 26.1%); most cases were mild or moderate in all treatment groups. Rates of serious AEs and discontinuations due to AEs were low in all groups.

CONCLUSIONS

In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; clear evidence of dose-dependent efficacy is unique to fesoterodine among antimuscarinics and other oral agents for the treatment of OAB. Fesoterodine 4 mg was significantly more effective than placebo on all outcomes except for improvements in UPS scores. These data support the benefit of having two doses of fesoterodine in clinical practice, with the recommended starting dose of 4 mg for all patients and the fesoterodine 8-mg dose available for patients who require a higher dose to achieve optimal symptom relief.

Links

  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    The Royal Hallamshire Hospital, Sheffield, UK.

    , , , , , ,

    Source

    BJU international 114:3 2014 Sep pg 418-26

    MeSH

    Adolescent
    Adult
    Aged
    Aged, 80 and over
    Benzhydryl Compounds
    Double-Blind Method
    Drug Administration Schedule
    Female
    Health Status
    Humans
    Male
    Middle Aged
    Patient Satisfaction
    Prospective Studies
    Quality of Life
    Surveys and Questionnaires
    Treatment Outcome
    Urinary Bladder, Overactive
    Urinary Incontinence, Urge
    Urological Agents

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24552358

    Citation

    Chapple, Christopher, et al. "Superiority of Fesoterodine 8 Mg Vs 4 Mg in Reducing Urgency Urinary Incontinence Episodes in Patients With Overactive Bladder: Results of the Randomised, Double-blind, Placebo-controlled EIGHT Trial." BJU International, vol. 114, no. 3, 2014, pp. 418-26.
    Chapple C, Schneider T, Haab F, et al. Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial. BJU Int. 2014;114(3):418-26.
    Chapple, C., Schneider, T., Haab, F., Sun, F., Whelan, L., Scholfield, D., ... Mangan, E. (2014). Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial. BJU International, 114(3), pp. 418-26. doi:10.1111/bju.12678.
    Chapple C, et al. Superiority of Fesoterodine 8 Mg Vs 4 Mg in Reducing Urgency Urinary Incontinence Episodes in Patients With Overactive Bladder: Results of the Randomised, Double-blind, Placebo-controlled EIGHT Trial. BJU Int. 2014;114(3):418-26. PubMed PMID: 24552358.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial. AU - Chapple,Christopher, AU - Schneider,Tim, AU - Haab,François, AU - Sun,Franklin, AU - Whelan,Laurence, AU - Scholfield,David, AU - Dragon,Erika, AU - Mangan,Erin, Y1 - 2014/07/01/ PY - 2014/2/21/entrez PY - 2014/2/21/pubmed PY - 2014/11/5/medline KW - dose comparison KW - dose response KW - dose titration KW - fesoterodine KW - overactive bladder KW - urgency urinary incontinence SP - 418 EP - 26 JF - BJU international JO - BJU Int. VL - 114 IS - 3 N2 - OBJECTIVE: To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post-baseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes (PROs). PATIENTS AND METHODS: This was a 12-week, randomised, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with overactive bladder (OAB) symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Patients were randomised (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; those randomised to fesoterodine 8 mg started with fesoterodine 4 mg once daily for 1 week, then 8 mg once daily for the remaining 11 weeks. Patients completed bladder diaries at baseline and weeks 4 and 12 and the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. The primary endpoint was change from baseline to week 12 in UUI episodes per 24 h. RESULTS: At week 12, patients receiving fesoterodine 8 mg (779 patients) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than patients receiving fesoterodine 4 mg (790) or placebo (386); diary-dry rate was significantly higher in the fesoterodine 8-mg group vs the fesoterodine 4-mg and placebo groups (all P < 0.05). At week 12, patients receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than patients receiving fesoterodine 4 mg or placebo (all P < 0.01). Patients receiving fesoterodine 4 mg had significantly greater improvements in UUI episodes, urgency episodes, and micturitions; significantly higher diary-dry rates; and significantly greater improvement in PPBC scores and OAB-q scores than patients receiving placebo (all P < 0.05). Dry mouth was the most commonly reported adverse event (AE) in the fesoterodine groups (placebo group, 3.4%; fesoterodine 4-mg group, 12.9%; fesoterodine 8-mg group, 26.1%); most cases were mild or moderate in all treatment groups. Rates of serious AEs and discontinuations due to AEs were low in all groups. CONCLUSIONS: In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; clear evidence of dose-dependent efficacy is unique to fesoterodine among antimuscarinics and other oral agents for the treatment of OAB. Fesoterodine 4 mg was significantly more effective than placebo on all outcomes except for improvements in UPS scores. These data support the benefit of having two doses of fesoterodine in clinical practice, with the recommended starting dose of 4 mg for all patients and the fesoterodine 8-mg dose available for patients who require a higher dose to achieve optimal symptom relief. SN - 1464-410X UR - https://www.unboundmedicine.com/medline/citation/24552358/Superiority_of_fesoterodine_8_mg_vs_4_mg_in_reducing_urgency_urinary_incontinence_episodes_in_patients_with_overactive_bladder:_results_of_the_randomised_double_blind_placebo_controlled_EIGHT_trial_ L2 - https://doi.org/10.1111/bju.12678 DB - PRIME DP - Unbound Medicine ER -