title: Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre Trial (ESPECIAL).
abstract: The aim was to assess the efficacy and safety of alprostadil in patients with peripheral arterial occlusive disease (PAOD) Fontaine Stage IV.
  
  
  
  This was a multinational, prospective, randomised, double blind, placebo controlled, parallel group trial. Patients with Stage IV PAOD were equally randomised to either 4 weeks of alprostadil treatment twice daily or to placebo treatment twice daily. The primary efficacy variables were the rate of complete healing of all necrosis and ulceration 12 weeks after the end of treatment and the frequency of major amputations 24 weeks after the end of treatment.
  
  
  
  A total of 840 patients were randomised between 2004 and 2013. At baseline, no major differences between treatment groups were found. The rate of "complete healing" was 18.4% in patients on alprostadil and 17.2% in patients on placebo. The rates of "major amputations" were 12.6% in patients on alprostadil and 14.6% in patients on placebo. The adjusted difference between alprostadil and placebo including their 95% confidence intervals was 1.1 (-4.0 to 6.3) for "complete healing" and -2.1 (-6.7 to 2.5) for "major amputations." In the subgroup of diabetic patients the rates of major amputations were numerically lower in the alprostadil than placebo group (10.6% vs. 17.4%). Within the total cohort a non-significant difference in "decrease in ulcer area ≥50%" was reached in 30.2% of patients on alprostadil and in 24.3% of patients on placebo at end of treatment.
  
  
  
  In this study, superiority of alprostadil over placebo could not be shown. Nevertheless, a slight numerical but not clinically relevant advantage for alprostadil emerged from the "area decrease of ulcers by ≥ 50%," indicating that a healing effect may have started. The results have to be considered in the light of several limitations in study design and conduct.
authors.affiliation: Max-Grundig-Klinik, Bühl, Germany; Practice for Cardiovascular Diseases and Academy for Vascular Diseases, Ettlingen, Germany. Electronic address: holger.lawall@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Lawall
authors.affiliation: A.V. Vishnevsky Institute of Surgery, Moscow, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Pokrovsky
authors.affiliation: Department of General and Vascular Surgery, University of Medical Sciences Poznan, Poznan, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Checinski
authors.affiliation: Department of Vascular Surgery, National Institute of Surgery and Transplantology, Kiev, Ukraine.
authors.forename: A
authors.initials: A
authors.lastname: Ratushnyuk
authors.affiliation: UCB Pharma, Monheim, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hamm
authors.affiliation: UCB Pharma, Monheim, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Randerath
authors.affiliation: UCB Pharma, Monheim, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Grieger
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: J W G
authors.initials: JWG
authors.lastname: Bentz
mesh_terms: D000368:Aged; D000527:Alprostadil / Q000009:adverse effects / Q000627:therapeutic use*; D000671:Amputation, Surgical; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D023821:Limb Salvage; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D014665:Vasodilator Agents; D000527:Alprostadil
keywords: Alprostadil; Critical limb ischaemia; Intervention; Peripheral arterial occlusive disease; Prostanoids