Charlotte Van Herzeele1, Jonathan Evans2, Paul Eggert3, Henri Lottmann4, Jens Peter Norgaard5, Johan Vande Walle6. 1. Department of Nephrology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: charlotte.vanherzeele@ugent.be. 2. Children's Renal & Urology Unit, Nottingham Children's Hospital, Nottingham University Hospitals NHS Trust, Queens, Medical Centre Campus, Derby Road, Nottingham NG7 2UH, UK. Electronic address: jonathan.evans@nuh.nhs.uk. 3. Klinik F. Allgemeine Pädiatrie, UKSH, Campus Kiel, 24105 Kiel, Schwanenweg 15, Germany. Electronic address: p.eggert@pediatrics.uni-kiel.de. 4. Sce de chirurgie viscérale pédiatrique (Pr Y. Aigrain), hopital Necker-Enfants-Malades, 149, rue de Sèvres, 75015 Paris, France. Electronic address: henri.lottmann@nck.aphp.fr. 5. Ferring, Global Scientific Affairs Urology, Ferring International PharmaScience Centre, Kay Fiskers Plads 11, DK-2300 Copenhagen, Denmark. Electronic address: jenspeter.norgaard@ferring.com. 6. Department of Nephrology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: johan.vandewalle@ugent.be.
Abstract
INTRODUCTION/ BACKGROUND: Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart. OBJECTIVE: The aim of this study was to identify any possible predictive factors to desmopressin response. STUDY DESIGN: This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression. RESULTS: Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume. DISCUSSION: Performing a secondary analysis is a limitation because the original study was not designed for that. A new prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2]. CONCLUSIONS: The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479.
RCT Entities:
INTRODUCTION/ BACKGROUND: Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart. OBJECTIVE: The aim of this study was to identify any possible predictive factors to desmopressin response. STUDY DESIGN: This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression. RESULTS: Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume. DISCUSSION: Performing a secondary analysis is a limitation because the original study was not designed for that. A new prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2]. CONCLUSIONS: The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479.