MP-06.02: Oral desmopressin in the treatment of nocturia in an aging population

MODERATED POSTER SESSIONS

MP-06: Moderated Poster Session 6 Overactive Bladder Friday, October 15 MP-06.01 The association of nocturia with sleep disorders, metabolic and chronic pulmonary conditions Ayik S2, Bal K1, Issi Y1, Bolukbasi A1, Akhan G3 Depts. of 1Urology; 2Chest Diseases;3Neurology, Ataturk Research and Training Hospital, Izmir, Turkey Introduction and Objectives: Nocturia is defined as awakening for passing urine after falling asleep at night. The International Continence Society defines nocturia as two or more nighttime voids. Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of upper airway obstruction that occur during sleep, and it is usually associated with a reduction in blood oxygen saturation. In this study we evaluated the prevalence of nocturia among different degrees of OSAS and its association with various chronic conditions. Materials and Methods: We retrospectively evaluated 730 patients diagnosed to have different degrees of OSAS according to polysomnographic evaluation (a diagnostic test during which a number of physiologic variables are measured and recorded during sleep). The distribution of patients according to OSAS severity was as follows: 160 patients had simple snoring (normal), 160 patients had mild OSAS, 128 patients had moderate OSAS and 282 patients had severe OSAS. Preva-

lence and frequency of nocturia in various degrees of OSAS was determined. We also assessed the association of nocturia with age, sex, body weight, Body mass index, neck circumference, apnea hypoapnea index, apnea duration, minimum oxygen saturation and clinical conditions such as diabetes mellitus, coronary heart disease and chronic pulmonary conditions. Results: The overall prevalence of nocturia (ⱖ2 wakes/night) was 51%. Table 1 demonstrates the clinical characteristics of patients with and without nocturia. Prevalence of nocturia in severe and moderate OSAS patients was significantly higher than mild OSAS and normal patients (58% and 57% respectively). Moreover the frequency of nocturia significantly increases as the severity of OSAS increases (1.4⫹1.0 wakes/night in mild OSAS vs 2.0⫹1.4 wakes/night in severe OSAS, p⫽0.001). Age, BMI, Apnea-hypopnea index, min oxygen saturation, average saturation, chronic obstructive pulmonary disease, hypertension and diabetes mellitus are found to be significant risk factors associated with nocturia(p⬍0.001). Conclusions: Nocturia is closely associated with OSAS. The frequency of nocturia per night increases as the severity of OSAS increases. The increased prevalence of nocturia in OSAS, diabetes mellitus, hypertension and chronic obstructive pulmonary disease indicates the complex physiologic background of this bothersome urologic symptom. Therefore when evaluating a patient for nocturia these associated factors should be kept in mind. A better understanding of nocturia and its association with different clinical conditions would help urologists to tailor an individualized approach according to patients’ conditions.

Table 1, MP-06.01

Age Female / Male Body mass index Neck circumference(cm) Apnea hypopnea index Chronic obstructive pulmonary disease(%) Hypertension Diabetes mellitus Coronary artery disease Average saturation (%) Min. oxygen saturation Apnea duration *:p⬍0.005

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Patients without nocturia N(358) 47.1⫹13.2* 127/231 30.5⫹5.5 39.6⫹3.7 23.9⫹25.4* 2.3* 15* 6.5* 3.8 92.0⫹4.3 83.4⫹11.6* 33.9⫹17

Nocturic patients (>2/night) N(372) 51.1⫹10.7* 129/243 32.2⫹5.8 40.4⫹3.8 33.6⫹31.1* 7.8* 27* 14.5* 7.8 77.7⫹15.4 38.8⫹24* 38.8⫹5.2

MP-06.02 Oral desmopressin in the treatment of nocturia in an aging population Yassin A1,2,3, Saad F4, Haider A5 1 Institute of Urology & Andrology, Segeberger Kliniken Norderstedt, Germany; 2 Dresden International University Program of Preventive Medicine, Dresden, Germany; 3Gulf Medical University School of Medicine, Ajman, UAE; 4Bayer Schering Pharma, Men’s Healthcare, Berlin, Germany & Gulf Medical University, Ajman, UAE, 5Private Urology Practice, Bremerhaven, Germany Introduction and Objective: Nocturia, defined as excessive urinating at night, is caused by different factors. If pathological causes such as infections, obstructions, etc. are excluded, an important cause in an aging population could be an insufficient level of ADH (D-arginine Vasopressin ⫽ DAVP) at night. The primary endpoint of this research was the proportion of patients with 50% or more reduction in nocturnal urine production resp. nocturnal voiding and elevation of urine osmolarity. The secondary endpoint is to prolong sleep duration by reducing nocturnal urine production. Materials and Methods: Forty patients (20 males and 20 females) with an average age of 61 years were screened using micturition diaries (defined as 2 or more nocturnal voidings), nocturnal polyuria greater than functional bladder capacity and measuring urine osmolarity by night. An open-label dose-titration period established an optimal dosage for the patients at 0.2 mg. After a one-week wash-out period patients were randomized to receive either 0.2 mg desmopressin (n⫽ 20) or placebo (n⫽20) for one month Results: The proportion of patients showing a 50% reduction of nocturia during the double-blind period was significantly higher in the group treated with desmopressin 0.2 mg (n⫽12 or 60%) compared with placebo (n⫽ 2 or 20%). Urine osmolarity was also significantly higher in the desmopressin group (810 mOsmol/kg H2O) compared to 630 mOsmol/kg H2O, with reduced volume of nocturnal voiding under drug. Sleep duration was improved under desmopressin with additional 180 min longer, than under placebo (42 min). Thus patients with desmopressin experienced more than five hours uninterrupted initial sleep per night (60%) compared with 6% under placebo. Nocturnal urine production under desmopressin declined from 1.51 ml/min to 0.84 ml/min, under placebo from 1.44 ml/min to 1.38 ml/min. All patients treated with desmopressin

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accepted to continue on the medication in an open-labelled phase for one year. Conclusions: Desmopressin is an effective treatment for nocturia associated with nocturnal polyuria, upon exclusion of other pathologic reasons such as infections, neuropathy, obstruction or anomalies etc. It is a useful treatment option in many aging patients of both genders. The most important result is the prolongation of sleep duration by reducing the number of nocturnal voidings. Treatment with desmopressin improved quality of life by decreasing the number of times the patients had to void at night and increasing the duration of unbroken sleep. MP-06.03 Delayed development of hyponatremia in the patients of nocturia managed with desmopressin acetate (DDAVP) Park J1, Kim D1, Kim C2, Cho W3, Chung H4 1 Daegu Catholic University Medical Center, Daegu; 2Kaemyung University Dongsan Hospital, Daegu; 3Dong-A University Hospital, Busan; 4Youngnam University Hospital, Daegu, South Korea Introduction and Objective: DDAVP is a very effective drug for the management of nocturnal polyuria. The pharmacologic actions of DDAVP are antidiuretic effects and activation of coagulation mechanism. The common adverse side effects are facial flushing, headache and serious complications like hyponatremia and coronary artery thrombosis were reported. Materials and Methods: There were 202 patients, diagnosed as nocturia due to nocturnal polyuria, included in this study. Average age was 68 years (age range: 5393). DDAVP was started 0.1mg as an initial dose and escalated into 0.2mg. Recent history of myocardial infarction, cerebrovascular accident and diuretic adminis-

trated patients were excluded. SerumNa/K was routinely measured at 1st month of DDAVP administration and bimonthly after then. Results: The incidence of hyponatremia was found in 12 patients (5.9%) at 2nd month and 10 month follow-up. Eight patients showed persistent low level of s-Na (range: 122-126 mEq/mL) and needed admission. Among them six patients were not controlled and should discontinue medications. Four patients’ s-Na level were in the range of 130-132 mEq/mL and managed successfully in outpatients clinic basis. Interpretation of results: Although adverse side effects are very rare with DDAVP treatment, hyponatremia may be a serious on,e especially in older age. Most reports associated with hyponatremia were developed 1-2 weeks after drug administration. According to our study, it can be developed in the 2nd month and lately in the 10th month. Conclusion: Development of hyponatremia in the DDAVP-managed nocturia patient is most commonly disclosed within 1-2 weeks after drug administration. In our study, delayed detection of hyponatremia after 2 months was observed and reported. Therefore, s-Na/K level should be measured several months after DDAVP administration. MP-06.04 Superior efficacy of fesoterodine over tolterodine: a pooled analysis of 2 head-to-head, placebo-controlled trials Van Kerrebroeck P1, Swift S2, Rovner E2, Creanga D3, Guan Z3, Gong J3 1 University Hospital Maastricht, Maastricht, The Netherlands, 2Medical University of South Carolina, Charleston, SC, USA; 3Pfizer Inc, New York, NY, USA Introduction and Objectives: We compared the efficacy and time course of response to fesoterodine (FESO) 8 mg vs tolterodine extended release (TER) 4 mg for treating overactive bladder (OAB)

symptoms in a predefined pooled analysis of data from 2 identical 12-wk randomized, double-blind, double-dummy, placebo (PBO)-controlled trials. Materials and Methods: Subjects (ⱖ18 y) enrolled in the 2 trials reported OAB symptoms for ⱖ3 mo and ⱖ8 micturitions and ⱖ1 urgency urinary incontinence (UUI) episode per 24 h in 3-day baseline diaries. Subjects randomized to FESO (4 mg for 1 wk, 8 mg for 11 wk), TER 4 mg, or PBO, completed 3-day diaries, Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS) at baseline and wks 1, 4, and 12 and Overactive Bladder Questionnaire (OAB-q) at baseline and wk 12. The primary endpoint was changed in UUI episodes from baseline to wk 12. Three-day diary dry rates were defined as the proportion of subjects with ⱖ1 UUI episode on baseline diary and 0 UUI episodes on diary at wk 1, 4, or 12. UUI, MVV, and severe urgency data were analyzed using Van Elteren test (a stratified Wilcoxon-Mann-Whitney test) with baseline quantiles as strata and presented as 5% Winsorized means. ANCOVA (protocol and centered baseline value as covariates) was used for other diary and OAB-q data; Cochran-Mantel-Haenszel test (stratified by protocol) was used for diary dry rate, PPBC, and UPS. Results: Pooled data included 4129 randomized subjects. At wk 12, improvements were significantly greater with FESO vs TER and PBO for UUI episodes (primary endpoint), micturitions, urgency (Figure), other diary endpoints (except nocturnal micturitions vs TER), PPBC, UPS, and all OAB-q domains. Diary dry rates were significantly higher with FESO vs TER and PBO (all P⬍0.05). At wk 4, FESO 8 mg was superior over TER 4 mg on UUI and most other diary endpoints, diary dry rates, PPBC, and UPS scores (P⬍0.05). Dry mouth and constipation rates were 28% and 5% with FESO 8 mg,

Figure 1, MP-06.04. Change in Diary Variables from Baseline (BL) to Weeks 1, 4, and 12. n⫽number of randomized subjects. *P⬍0.05 TER vs PBO; †P⬍0.05 FESO vs PBO; ‡P⬍0.05 FESO vs TER

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