Elsevier

European Urology

Volume 52, Issue 1, July 2007, Pages 221-229
European Urology

Voiding Dysfunction
Desmopressin in the Treatment of Nocturia: A Double-Blind, Placebo-Controlled Study

https://doi.org/10.1016/j.eururo.2007.01.027Get rights and content

Abstract

Objectives

To investigate efficacy, safety, and impact on quality of sleep of desmopressin in the treatment of nocturia.

Methods

Adults aged ≥18 yr with nocturia (≥2 voids/night) received desmopressin tablets (0.1, 0.2, or 0.4 mg) during a 3-wk dose-titration period. Patients should show sufficient response during the dose-titration period (≥20% reduction in nocturnal diuresis) and a return of nocturnal diuresis to ≥80% of baseline levels during washout. Eligible patients then entered a 3-wk double-blind treatment period and received either desmopressin or placebo.

Results

127 patients were randomised to either desmopressin (n = 61) or placebo (n = 66). Twenty (33%) desmopressin-treated patients compared with seven (11%) placebo-treated patients showed a clinical response, defined as a ≥50% reduction in the number of nocturnal voids compared with baseline (p = 0.0014). Compared with placebo, desmopressin resulted in a significant reduction in the mean number of nocturnal voids (39% reduction with desmopressin vs. 15% with placebo; absolute difference −0.84, p < 0.0001) and duration of the first sleep period (prolonged by 108 min with desmopressin vs. 41 min with placebo; p < 0.0001). Quality of sleep was also improved with desmopressin versus placebo (statistically significant for one of the two parameters evaluated). Adverse events were mainly mild.

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 be improved.

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.

References (22)

  • P. van Kerrebroeck et al.

    The standardisation of terminology in nocturia: report from the standardisation sub-committee of the International Continence Society

    Neurourol Urodyn

    (2002)
  • Cited by (0)

    The study was supported by a grant from Ferring Pharmaceuticals A/S.

    View full text