International drug study shows rapid
improvement in overactive bladder symptoms
Professor Linda Cardozo from the Department of Urogynaecology at King’s College Hospital in London, has led an international study to measure the effectiveness of solifenacin in improving overactive bladder symptoms. The study involved 105 urology centres from 14 European countries, with 863 patients.
The 16-week study was a double-blind randomised study, with the researchers and the patients being unaware of which patients were taking solifenacin and which were taking a placebo. Three times as many patients took the active drug as the placebo. The study was carried out in two 8-week segments, with 640 patients being given 5 mg daily of solifenacin in the first segment and the remaining 223 receiving the placebo.
The study was conducted to see what effect solifenacin had on overactive bladder problems, and is the first study to assess urgency as the primary endpoint using the four-point Patient Perception of Intensity and Urgency Scale (PPIUS) with grades three and four representing urgency and urgency incontinence. Other outcome measures used were the six-point Patients Perception of Bladder Condition score, visual analogue scales and patient diaries.
Professor Cardozo and her team found that there was an average 70% reduction in severe urgency and urgency reported with incontinence patients taking solifenacin, as measured by the PPIUS, compared with 50% for those taking the placebo. Levels of urgency, maximum urgency intensity and urgency bother also showed statistically significant improvements. These improvements were seen as early as day three.
Severe side effects were reported in less than 4% of the patients, and only 3.6% of the people on solifenacin stopped taking the drug.
This study shows that solifenacin was consistently effective at reducing urgency and other symptoms associated with an overactive bladder.
Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomised, double-blind, placebo-controlled, rising-dose trial
Linda Cardozo, Elke Heßdörfer, Rodolfo Milani, Pedro Araño, Luc Dewilde, Mark Slack, Ted Drogendijk, Mark Wright and John Bolodeoku for the SUNRISE Study Group
BJU International 102 (9), 1120-1127. doi:10.1111/j.1464-410X.2008.07939.x
OBJECTIVES - To examine the effects of the antimuscarinic agent solifenacin on urinary urgency, using a range of novel and established outcome measures, as urgency is the principal symptom of the overactive bladder syndrome (OAB).
PATIENTS AND METHODS - The study (SUNRISE, solifenacin in the treatment of urgency symptoms of OAB in a rising dose, randomized, placebo-controlled, double-blind, efficacy trial) was a randomized, double-blind, 16-week, placebo-controlled, multicentre study of solifenacin 5/10 mg in 863 patients with symptoms of OAB for ≥ 3 months. Theprimary efficacy variable was the change from baseline to endpoint in the number of episodes of severe urgency with or without urgency incontinence per 24 h, as measured using the Patient Perception of Intensity of Urgency Scale, grade 3 + 4. Secondary efficacy variables included patient-reported outcomes for bladder condition, urgency bother and treatment satisfaction. A 3-day voiding diary was used to record micturition frequency and episodes of urgency and incontinence. A 7-day diary was used to assess speed of onset of effect.
RESULTS - Solifenacin 5/10 mg was significantly more effective than placebo in reducing the mean number of episodes of severe urgency with or without incontinence per 24 h from baseline to endpoint (2.6 vs1.8, P < 0.001). There were also statistically significant differences in favour of solifenacin 5/10 mg over placebo for all secondary variables measured at endpoint, including patient-reported outcomes. There was a significant improvement in urgency as early as day 3 of treatment. Treatment emergent adverse events with solifenacin 5/10 mg were mainly mild or moderate in severity, and only led to discontinuation in 3.6% of patients.
CONCLUSION - Solifenacin significantly reduced the number of urgency episodes and the extent of urgency bother, and was well tolerated; it was effective as early as
day 3 of treatment.
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Linda Cardozo is Professor of Urogynaecology and Consultant Gynaecologist at King’s College Hospital, London. She trained at Liverpool University Medical School and qualified MBChB in 1974. Thereafter she developed a special interest in urinary incontinence at St George’s Hospital under the aegis of Professor Stuart Stanton obtaining an MD in 1979 and her MRCOG in 1980.
Following her appointment as a Consultant Obstetrician and Gynaecologist in 1985 she continued to develop her interest in all aspects of urogynaecology including the influence of hormones on the lower urinary tract, conservative and surgical treatment of stress incontinence, the patho-physiology and pharmacological treatment of detrusor overactivity and the management of urogenital prolapse.
Professor Cardozo now heads a busy and productive tertiary referral urogynaecology department at King’s College Hospital. She has a large clinical workload dealing with complex urogynaecological problems in a supra-regional tertiary referral unit teaching medical students, training junior doctors and undertaking clinical research. Her publications include more than 300 original papers in peer review journals and 17 books.
Professor Cardozo is President of the Association of Chartered Physiotherapists in Women's Health. She is also a Past President of the International Urogynaecological Association, Past President of the Section of Obstetrics and Gynaecology of the Royal Society of Medicine. She was the founding Chairman of the British Society of Urogynaecology and a Past Chairman of the British Menopause Society and of the Education Committee of International Continence Society. She is currently Vice Chairman of the World Health Organisation International Consultation on Incontinence.
How should patients with an overactive bladder manipulate their fluid intake?
Hashim Hashim and Paul Abrams
Abstract: To assess how the symptoms of overactive bladder (OAB) syndrome in adults are affected by decreasing or increasing fluid input, and the effect of fluid manipulation on quality of life.
Patients and Methods: Adults with symptoms of OAB were randomized in a two-group, prospective, cross-over trial following a 4-day screening period (to establish baseline values) using frequency/volume charts, if they had a mean of eight or more voids and one or more urgency and/or urgency incontinence episodes in 24-h. Patients were asked to either increase or decrease their fluid intake, from baseline, as follows: group 1, 4 days drinking 25% less than baseline, and 2 days normal, then 4 days at 50% less than baseline, and 2 days normal, then 4 days at 25% more than baseline, and 2 days normal, and then 4 days at 50% more than baseline. Group 2 did the reverse. The primary endpoint was the change in the frequency of unwanted events during a 24-h period.
Results: In all, 67 patients were contacted, 40 recruited and 24 were eligible. There was a significant reduction in frequency, urgency and nocturia when patients decreased their fluid input by 25%. Increasing fluid input by 25% and 50% resulted in a worsening of daytime frequency. Overall there was no statistically significant improvement in quality of life but there was some subjective improvement in urgency and nocturia, as measured by a validated instrument, in the group that decreased their fluid input by 25%; ≈300 mL of daily fluid came from water-containing foods.
Conclusions: Fluid manipulation is a cheap, noninvasive and easy way to help control the symptoms of OAB. Patients have difficulty in either decreasing or increasing their fluid input by 50%. Patients can now be told to expect a significant improvement in urgency, frequency and nocturia episodes if they reduce their fluid input by 25%.
Published Online: Feb 18 2008 12:00AM
DOI: 10.1111/j.1464-410X.2008.07463.x
Tolterodine Extended Release With or Without Tamsulosin in Men With Lower Urinary Tract Symptoms and Overactive Bladder: Effects on Urinary Symptoms Assessed by the International Prostate Symptom Score
Steven A. Kaplan, Claus G. Roehrborn, Michael Chancellor, Martin Carlsson, Tamara Bavendam, Zhonghong Guan
Abstract: To evaluate the efficacy of tolterodine extended-release (ER) plus tamsulosin on lower urinary tract symptoms (LUTS) as assessed by changes in the International Prostate Symptom Score (IPSS) in men who met symptom entry criteria for both overactive bladder (OAB) and benign prostatic hyperplasia (BPH) trials.
Patients and Methods: Men aged ≥40 years with an IPSS of ≥12 and diary-documented OAB symptoms (≥8 voids/24 h and≥3 urgency episodes/24 h, with or without urgency urinary incontinence) who reported at least moderate problems related to their bladder condition were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER (4 mg) + tamsulosin (0.4 mg) once daily for 12 weeks. Patients completed the IPSS at baseline and at 1, 6 and 12 weeks.
Results: Patients receiving tolterodine ER + tamsulosin had significantly greater improvements than those taking placebo on IPSS storage subscale scores and scores for all three individual storage items included on the IPSS (urinary frequency, urgency, and nocturnal micturitions) by 12 weeks. Storage subscale and urgency scores were significantly improved vs placebo at 1 and 6 weeks, whereas frequency scores were significantly improved at 6 weeks. Changes in IPSS storage subscale and individual storage item scores in the tolterodine ER and tamsulosin monotherapy groups were not significantly different from placebo at most time points. IPSS voiding subscale scores and scores for three of four individual voiding items (sensation of incomplete emptying, intermittency, and weak stream) were significantly improved by 12 weeks for patients receiving tamsulosin monotherapy vs placebo. Voiding subscale and intermittency scores were significantly improved vs placebo at 1 week; weak stream scores were significantly improved at 1 and 6 weeks. The IPSS voiding subscale and individual voiding item scores in the tolterodine ER + tamsulosin and tolterodine ER groups were not significantly different from placebo at most time points.
Conclusions: In this distinct clinical research population of men who met traditional symptom entry criteria for both OAB and BPH trials, tolterodine ER + tamsulosin was significantly more effective than placebo in treating storage LUTS, including OAB symptoms. Tamsulosin monotherapy produced significant improvements in voiding LUTS
Published Online: May 28 2008 12:00AM
DOI: 10.1111/j.1464-410X.2008.07761.x
The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study
Karin S. Coyne, Chris C. Sexton, Debra E. Irwin, Zoe S. Kopp, Con J. Kelleher, Ian Milsom
Abstract: To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS.
Subjects and Methods: A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences.
Results: Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups.
Conclusion: OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes
Published Online: Mar 11 2008 12:00AM
DOI: 10.1111/j.1464-410X.2008.07573.x
