title: Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial.
abstract: BACKGROUND
  Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation.
  
  
  OBJECTIVE
  The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management.
  
  
  METHODS
  Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study.
  
  
  RESULTS
  Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved.
  
  
  CONCLUSIONS
  Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.
authors: Centre for Pulmonary Hypertension, Thorax Clinic at the University of Heidelberg, Heidelberg, Germany.
authors: Ekkehard
authors: E
authors: Grünig
authors: Nicola
authors: N
authors: Benjamin
authors: Tobias J
authors: TJ
authors: Lange
authors: Ulrich
authors: U
authors: Krueger
authors: Hans
authors: H
authors: Klose
authors: Claus
authors: C
authors: Neurohr
authors: Heinrike
authors: H
authors: Wilkens
authors: Michael
authors: M
authors: Halank
authors: Hans-Jürgen
authors: HJ
authors: Seyfarth
authors: Matthias
authors: M
authors: Held
authors: Andrew
authors: A
authors: Traube
authors: Michelle
authors: M
authors: Pernow
authors: E Robert
authors: ER
authors: Grover
authors: Benjamin
authors: B
authors: Egenlauf
authors: Felix
authors: F
authors: Gerhardt
authors: Thomas
authors: T
authors: Viethen
authors: Stephan
authors: S
authors: Rosenkranz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005858:Germany; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome; D014261:Tricuspid Valve / Q000000981:diagnostic imaging; D014655:Vascular Resistance; D000070857:Walk Test
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D011464:Epoprostenol; C427248:treprostinil