title: Effects of tadalafil once daily or on demand versus placebo on time to recovery of erectile function in patients after bilateral nerve-sparing radical prostatectomy.
abstract: OBJECTIVE
  We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP).
  
  
  METHODS
  Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country).
  
  
  RESULTS
  A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW.
  
  
  CONCLUSIONS
  Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo.
authors.affiliation: Department of Urology, Hospital La Zarzuela, Madrid, Spain, ignacio@moncada.name.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moncada
authors.forename: Fermín R
authors.initials: FR
authors.lastname: de Bethencourt
authors.forename: Enrique
authors.initials: E
authors.lastname: Lledó-García
authors.forename: Javier
authors.initials: J
authors.lastname: Romero-Otero
authors.forename: Carmen
authors.initials: C
authors.lastname: Turbi
authors.forename: Hartwig
authors.initials: H
authors.lastname: Büttner
authors.forename: Carsten
authors.initials: C
authors.lastname: Henneges
authors.forename: Juan I
authors.initials: JI
authors.lastname: Martinez Salamanca
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010410:Penile Erection; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D011468:Prostatectomy / Q000009:adverse effects*; D020127:Recovery of Function; D000068581:Tadalafil / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil