title: A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale.
abstract: BACKGROUND
  Livedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted.
  
  
  OBJECTIVE
  The aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy.
  
  
  METHODS
  We performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks.
  
  
  RESULTS
  Enrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014.
  
  
  CONCLUSIONS
  Livedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa-dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis.
  
  
  BACKGROUND
  Trial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical Trials Register (DRKS): DRKS00004652; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004652 (Archived by WebCite at http://www.webcitation.org/6UCIAKyCS).
authors.affiliation: Clinical Trial Support, Muenster, Germany.
authors.forename: Attyla
authors.identifier: http://orcid.org/0000-0001-8413-7626
authors.initials: A
authors.lastname: Drabik
authors.forename: Carina
authors.identifier: http://orcid.org/0000-0002-9665-7263
authors.initials: C
authors.lastname: Hillgruber
authors.forename: Tobias
authors.identifier: http://orcid.org/0000-0002-3631-8841
authors.initials: T
authors.lastname: Goerge
keywords: leg ulcer; rare disease; rivaroxaban; skin infarction; vasculitis