title: Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study.
abstract: OBJECTIVE
  To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc).
  
  
  METHODS
  Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05).
  
  
  RESULTS
  Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).
  
  
  CONCLUSIONS
  The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit.
  
  
  BACKGROUND
  NCT01295736.
authors.affiliation: Médecine Interne, Hopital Huriez, Université de Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Médecine Interne, Hopital Huriez, Université de Lille, Lille, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hatron
authors.affiliation: Médecine Vasculaire, CHU, Grenoble, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Carpentier
authors.affiliation: Médecine Interne, Hôpital Hôtel Dieu, Nantes, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Agard
authors.affiliation: Rhumatologie, Hôpital Hautepierre, Strasbourg, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chatelus
authors.affiliation: Médecine Interne, CHR Rennes Sud, Rennes, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jego
authors.affiliation: Médecine Interne, AP-HP, Hôpital Cochin, Université Paris Descartes, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.affiliation: Médecine Interne, Hôpital de l'Archet 1, Nice, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Queyrel
authors.affiliation: Médecine Interne, Hôpital Dupuytren, Limoges, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fauchais
authors.affiliation: Médecine Vasculaire, Hôpital Saint Joseph, Paris, France.
authors.forename: Ulrique
authors.initials: U
authors.lastname: Michon-Pasturel
authors.affiliation: Médecine Interne, Hôpital Robert Debré, Reims, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Jaussaud
authors.affiliation: Médecine Interne 2, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.affiliation: Médecine Interne, Hôpital Nord, Aix Marseille Université, Marseille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Granel
authors.affiliation: Médecine Interne, Hôpital Bretonneau, Tours, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.affiliation: Médecine Interne, Hôpital Saint Louis, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge-Bancel
authors.affiliation: Medicine interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), AP-HP, Hôpital Saint Antoine, Paris, France.
authors.forename: Arsène
authors.initials: A
authors.lastname: Mekinian
authors.affiliation: Rhumatologie A, Hôpital Cochin, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Avouac
authors.affiliation: Médecine Interne, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Desmurs-Clavel
authors.affiliation: Orgamétrie Biostatistiques, Roubaix, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Clerson
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D057194:Intention to Treat Analysis; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000150:complications*; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D012883:Skin Ulcer / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
keywords: Autoimmune Diseases; Patient perspective; Treatment