Objective
Evaluation of safety and efficacy of desmopressin/tolterodine combination therapy in women.
Methods
This double‐blind, randomized, proof‐of‐concept study enrolled 106 patients (≥18 years), with overactive bladder (OAB) and nocturia, with ≥2 nocturnal voids, receiving a 3‐month once‐daily combination (desmopressin 25 µg, orally‐disintegrating tablets [ODT]/tolterodine 4 mg [Detrol® LA]; n = 49) or monotherapy (tolterodine 4 mg/placebo ODT; n = 57). Primary endpoint was change from baseline in mean number of nocturnal voids. Secondary endpoints were change from baseline in nocturnal voided volume, time to first nocturnal void, and quality‐of‐life. Post‐hoc exploratory analysis were performed for patients with and without baseline nocturnal polyuria (NP, n = 47 each).
Results
Overall population showed a non‐significant reduction in mean number of nocturnal voids with combination versus monotherapy (full analysis set: adjusted treatment contrast [TC], −0.34; P = 0.112). Change in mean nocturnal void volume (TC, −64.16 mL; P = 0.103), mean time to first nocturnal void (TC, 18.00 min; P = 0.385) and Nocturia Impact (NI) Diary© scores were comparable. In post‐hoc analysis, NP patients showed a benefit with combination versus monotherapy for nocturnal void volume (P = 0.034) and time to first nocturnal void (P = 0.045), and a non‐significant improvement in NI Diary© scores. Safety profile was comparable between treatments. A single transient event of asymptomatic clinically significant hyponatremia in combination group resolved subsequently.
Conclusion
Low‐dose desmopressin could be safely combined with tolterodine for treating nocturia in women with OAB, with a significant benefit in women with NP. Further, prospective validation studies of combination therapy are warranted in mixed NP/OAB population, based on this favorable proof‐of‐concept finding.
These authors, that are well recognised as specialists in the field of Functional Urology and more especially in Nocturia, evaluated the safety and efficacy of a 3-month once-daily combination of 25 µg desmopressin orally-disintegrating tablets and tolterodine 4 mg ODT (n = 49) or monotherapy with 4 mg ODT tolterodine (n = 57) in women with overactive bladder and nocturia (≥2 nocturnal voids). They used as primary endpoint the change from baseline in mean number of nocturnal voids, and as secondary endpoints the change from baseline in nocturnal voided volume, time to first nocturnal void, and quality-of-life. Post-hoc exploratory analysis were performed for patients with and without baseline nocturnal polyuria (NP, n = 47 each).The overall population showed a non-significant reduction in mean number of nocturnal voids with combination versus monotherapy, but… in a post-hoc analysis, patients with NP showed a benefit with combination versus monotherapy for nocturnal voided volume and time to first nocturnal void. They conclude that low-dose desmopressin could be safely combined with tolterodine for treating nocturia in women with OAB, with a significant benefit in women with NP. They further indicate that prospective validation studies of combination therapy are warranted in mixed NP/OAB population, based on this favourable proof-of-concept finding.
It seems obvious that screening for NP is an important predictive factor for success with desmopressin therapy also in women with the OAB/Nocturia combination.