Nocturia is mostly related to Nocturnal Polyuria (NP), and is a common finding in patients with Overactive Bladder (OAB). Conventional therapy with antimuscarinics do not address nocturia, leading to a poor Quality of Life (QoL). There is a lack of Randomised Controlled Trials (RCT) with combination therapies that address OAB, and nocturia. This post-hoc analysis from a small proof-of-concept RCT, first of its kind, evaluated the efficacy of a combination therapy (desmopressin 25μg orally disintegrating tablets + tolterodine 4mg capsules) in women with OAB, and nocturia due to NP (nocturnal volume ≥33% of total daily urine volume at Baseline).
Study included 94 women (≥18 years) with OAB and nocturia who received either a combination therapy or monotherapy (tolterodine 4mg), once-daily at bedtime for 3 months. Treatment contrasts are presented for change in mean number and volume of nocturnal voids, mean time to first nocturnal void (using an e-Diary), impact of nocturia (using Nocturia Impact [NI] Diary©), and impact on sleep quality (Sleep Rating Scale ranging from 0-10) [SRS]). NI Diary© consists of 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The minimally important difference for NI Diary© total score has been estimated to be between 5-10 points. The changes from Baseline during 3 months of treatment were analysed using repeated measures analysis of covariance.
The combination therapy improved nocturia symptoms vs. monotherapy in NP group, reaching statistical significance for change in mean time to first nocturnal void and mean volume of nocturnal voids (p<0.05). The numerical improvement in NI Diary© total and impact scores and sleep quality also favoured combination therapy in NP group (p>0.05) (Table). There were no differences between the treatments in non-NP group.
Table: Change in nocturia symptoms, NI Diary© scores, and SRS from Baseline to Month 3 in patients with and without NP in FAS
| NP group Combination, n=25 Monotherapy, n=22 |
Non‑NP group Combination, n=20 Monotherapy, n=27 |
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| Treatment comparison; Combination therapy vs. Monotherapy group | ||
| Treatment contrast for the change in mean number of nocturnal voids from Baseline | -0.62 | 0.04 |
| p-value | 0.064 | 0.881 |
| Treatment contrast for the change in mean time to first nocturnal void from Baseline (min) | 65.11 | -2.62 |
| p-value | 0.045 | 0.923 |
| Treatment contrast for the change in mean volume of nocturnal voids from Baseline (mL) | -166.0 | 3.22 |
| p-value | 0.034 | 0.919 |
| Treatment contrast for the change in mean NI Diary© total score from Baseline (Q1-Q11) | -10.58 | 2.59 |
| p-value | 0.059 | 0.635 |
| Treatment contrast for the change in mean NI Diary© overall impact from Baseline (Q12) | -13.85 | 3.42 |
| p-value | 0.062 | 0.532 |
| Treatment contrast for the change in the three SRS from Baseline (range)* | 0.48 to 0.62 | -0.08 to 0.27 |
| FAS=full analysis set, NI=nocturia impact; NP=nocturnal polyuria, SRS=sleep rating scale. *p >0.05, summary of the three sleep rating scales |
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A low-dose desmopressin can be beneficially combined with tolterodine for treating nocturia due to NP in women with OAB. The improvement in QoL was clinically relevant. These findings may be relevant to clinical practice where combination therapy can be used in mixed populations since NP is common in patients with OAB.
