title: Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial.
abstract: BACKGROUND
  The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion.
  
  
  METHODS
  A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature.
  
  
  RESULTS
  Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions.
  
  
  CONCLUSIONS
  The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL. Electronic address: bbourge@uab.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bourge
authors.affiliation: Brigham & Women's Hospital, Boston, MA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Waxman
authors.affiliation: University of Chicago Medical Center, Chicago, IL.
authors.forename: Mardi
authors.initials: M
authors.lastname: Gomberg-Maitland
authors.affiliation: VA Greater Los Angeles Healthcare System and UCLA School of Medicine, Los Angeles, CA.
authors.forename: Shelley M
authors.initials: SM
authors.lastname: Shapiro
authors.affiliation: Orlando Regional Medical Center, Orlando, FL.
authors.forename: James H
authors.initials: JH
authors.lastname: Tarver
authors.affiliation: Aurora St. Luke's Medical Center, Milwaukee, WI.
authors.forename: Dianne L
authors.initials: DL
authors.lastname: Zwicke
authors.affiliation: Arizona Pulmonary Specialists, Ltd, St. Louis, MO.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Feldman
authors.affiliation: Washington University School of Medicine, St. Louis, MO.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Chakinala
authors.affiliation: Mayo Clinic Rochester, Rochester, MN.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Frantz
authors.affiliation: University of Texas Southwestern Medical Center, Rochester, MN.
authors.forename: Fernando
authors.initials: F
authors.lastname: Torres
authors.affiliation: Medtronic, Inc, Minneapolis, MN.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cerkvenik
authors.affiliation: Medtronic, Inc, Minneapolis, MN.
authors.forename: Marty
authors.initials: M
authors.lastname: Morris
authors.affiliation: Medtronic, Inc, Minneapolis, MN.
authors.forename: Melissa
authors.initials: M
authors.lastname: Thalin
authors.affiliation: United Therapeutics Corporation, Research Triangle Park, NC.
authors.forename: Leigh
authors.initials: L
authors.lastname: Peterson
authors.affiliation: UC San Diego Division of Pulmonary & Critical Care Medicine, La Jolla, CA.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage; D061807:Catheter Obstruction / Q000706:statistics & numerical data; D055499:Catheter-Related Infections / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000209:etiology; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy*; D015918:Infusion Pumps, Implantable / Q000009:adverse effects* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D011446:Prospective Studies; D014481:United States
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil
keywords: central venous catheters; drugs; health-related quality of life; pulmonary arterial hypertension; pulmonary hypertension; treprostinil