title: Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT).
abstract: BACKGROUND
  The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear.
  
  
  OBJECTIVE
  The primary objective was to compare the efficacy of tadalafil 5mg once daily and tadalafil 20mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥ 22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length.
  
  
  METHODS
  Randomised, double-blind, double-dummy, placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate (Gleason ≤ 7) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada.
  
  
  METHODS
  1:1:1 randomisation to 9 mo of treatment with tadalafil 5mg once daily, tadalafil 20mg on demand, or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily (all patients).
  
  
  METHODS
  Logistic regression, mixed-effects model for repeated measures, and analysis of covariance, adjusting for treatment, age, and country, were applied to IIEF-EF scores ≥ 22, SEP-3, and penile length.
  
  
  CONCLUSIONS
  Four hundred twenty-three patients were randomised to tadalafil once daily (n=139), on demand (n=143), and placebo (n=141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores ≥ 22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6-2.1; p=0.675) and 0.9 (95% CI, 0.5-1.7; p=0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: ΔIIEF-EF ≥ 4) in both tadalafil groups; for SEP-3 (MCID ≥ 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p=0.016; SEP-3: p=0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1mm; 95% CI, 0.4-7.8; p=0.032).
  
  
  CONCLUSIONS
  Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01026818.
authors.affiliation: Vita Salute San Raffaele University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: University of Western Ontario, London, Ontario, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Brock
authors.affiliation: Universitätsklinikum Leipzig, Leipzig, Germany.
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.affiliation: Memorial Sloan-Kettering Cancer Centre, New York, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Mulhall
authors.affiliation: Hospital La Zarzuela, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moncada
authors.affiliation: University Hospital North Norway, Tromso, Norway.
authors.forename: Hitendra R H
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Hôpital Universitaire Archet 2, Nice, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chevallier
authors.affiliation: Uniwersyteckie Centrum Kliniczne, Gdansk, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Krajka
authors.affiliation: Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Henneges
authors.affiliation: Eli Lilly Canada Inc., Toronto, Ontario, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dickson
authors.affiliation: Lilly Deutschland GmbH, Bad Homburg, Germany. Electronic address: buettnerh@lilly.com.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Büttner
mesh_terms: D000230:Adenocarcinoma / Q000601:surgery*; D000368:Aged; D002243:Carbolines / Q000008:administration & dosage*; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059351:Organ Sparing Treatments; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D011468:Prostatectomy / Q000009:adverse effects / Q000379:methods*; D011471:Prostatic Neoplasms / Q000601:surgery*; D020127:Recovery of Function; D000068581:Tadalafil
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil
keywords: Clinical trials; Erectile dysfunction; Nerve-sparing prostatectomy; Penile function; Phosphodiesterase type 5 inhibitors; Prostate cancer; Radical prostatectomy; Rehabilitation; Tadalafil once a day