Voiding DysfunctionDesmopressin in the Treatment of Nocturia: A Double-Blind, Placebo-Controlled Study☆
Introduction
Desmopressin is a synthetic analogue of arginine vasopressin (AVP), commercially available since 1974. Desmopressin is proven effective for the treatment of polyuric conditions such as primary nocturnal enuresis and central diabetes insipidus (CDI) [1], [2], [3]. Reductions in AVP secretion may play a role in these conditions; in particular, the role of AVP deficiency in CDI is well documented. Antidiuresis induced by desmopressin is more potent than AVP, resulting in an increased urine osmolality and a decreased urine output. It has, therefore, been considered by several investigators for the treatment of nocturia with positive results [4], [5], [6], [7] and is now an established treatment for this indication, registered for use in many countries worldwide.
Nocturia, waking at night one or more times to void [8], is a recognised clinical condition that clearly benefits from antidiuretic treatment [9]. Nocturia is a common condition [10], [11] that is not only bothersome [12] but can have a marked impact on the sufferer’s quality of life (QOL) [13] and sleep patterns. Nocturnal polyuria, or the overproduction of urine at night, is one of the main causes of nocturia (approximately 70% of cases) [14]. In addition to desmopressin, conservative treatment approaches, such as behavioural modification, anticholinergic therapy, and timed use of diuretics also exist [15], [16]. However, these approaches are generally ineffective in treating nocturia in which nocturnal polyuria is a major contributory factor [16].
Previous experience suggests that the optimal dose of desmopressin differs among patients. Therefore, in phase 3 studies investigating the efficacy and safety of desmopressin in the management of nocturia in adults, an open-label dose-titration phase has been used to establish the optimal dose giving maximal reduction in nocturnal diuresis per patient. Two of these studies [6], [7] reported that the desmopressin tablet is an effective and well-tolerated treatment for nocturia in both men and women. The present study was designed to confirm the findings of these two studies and extend desmopressin experience in the treatment of nocturia.
Section snippets
Study design
This multicentre study was conducted in men and women aged ≥18 yr at 18 centres across France, Germany, Sweden, and The Netherlands. The study design was similar to the initial phase 3 studies [6], [7], comprising patient screening for eligibility, an open-label dose-titration phase of up to 3 wk to determine patients’ optimal desmopressin dose, a 1-wk washout period, and randomised, double-blind desmopressin or placebo treatment for 3 wk (Fig. 1). The latter phase was to establish clinical
Patient disposition
In total, 271 patients were screened at 18 centres: Germany (4), Sweden (5), the Netherlands (4), and France (5). Of these, 184 patients entered the dose-titration phase and received at least one dose of study medication (Fig. 2); the main reason for screening failure was not meeting the eligibility criterion of at least two voids per night. Immediately following the washout period, 127 patients were randomised to receive either desmopressin (48%) or placebo (52%); reasons for withdrawal after
Discussion
This study confirms the findings of others [6], [7], that desmopressin is an effective treatment for patients with nocturia. The antidiuretic effect of desmopressin results in a higher clinical response, a decrease in the mean number of nightly voids, and a prolongation of the first sleep period, all these end points being statistically significantly superior for desmopressin compared with placebo. The results of exploratory questions also indicated an improvement in sleep quality in patients
Conclusions
Oral desmopressin tablets provide an effective and well-tolerated treatment for nocturia. Compared with placebo, nocturnal voiding frequency is reduced, duration of the first sleep period is increased, and sleep quality may also be improved.
Conflicts of interest
Dr van Kerrebroeck has been a trial investigator with Ferring Pharmaceuticals and a speaker at symposia organised by Ferring Pharmaceuticals.
Dr Thüroff is Co-editor of the British Journal of Urology International, Section editor of Urology, Scientific Advisory Board Member for Lilly, and Scientific Advisory Board Member for Bayer/Novartis and has received a research grant from Pfizer.
Dr Riis and Dr Nørgaard are both full-time employees of Ferring Pharmaceuticals.
Acknowledgements
The authors would like to thank the investigators at the four European trial centres in for their contribution to this study.
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The study was supported by a grant from Ferring Pharmaceuticals A/S.