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Transition From IV Epoprostenol to Subcutaneous Treprostinil in Pulmonary Arterial Hypertension^*

A Controlled Trial

Melvyn Rubenfire, MD; Vallerie V. McLaughlin, MD, FCCP; Roblee P. Allen, MD, FCCP; Greg Elliott, MD; Myung H. Park, MD; Michael Wade, PhD and Robert Schilz, DO, PhD

^* From the University of Michigan Health System (Drs. Rubenfire and McLaughlin), Ann Arbor, MI; UC Davis Medical Center (Dr. Allen), Sacramento, CA; LDS Hospital and the University of Utah (Dr. Elliot), Salt Lake City, UT; University of Maryland School of Medicine (Dr. Park), Baltimore, MD; United Therapeutics Corporation (Dr. Wade), Research Triangle Park, NC; and University Hospitals of Cleveland (Dr. Schilz), Cleveland, OH. For the Treprostinil Phase 4 Study Group: R. Clayton, RN, and S. McDevitt, RN; MSN, University of Michigan, Ann Arbor, MI; L. Latham, RN, and L. Slaughter RN, University Hospitals of Cleveland, Cleveland, OH; A. Hoso, RN, UC Davis Medical Center, Sacramento, CA; N. Kitterman, RN, LDS Hospital, Salt Lake City, UT; B. Harris, RN, and M. Franklin, LNP, Oschner Clinic, New Orleans, LA; J. Sigman, C. Arneson, M.Stat, W. DellaMaestra, S. McSwain, D. Preston, DVM, and R. Jeffs, PhD, United Therapeutics Corporation, Research Triangle Park, NC.

Correspondence to: Melvyn Rubenfire, MD, University of Michigan, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48106-0363; e-mail: mrubenfi{at}umich.edu

Abstract

Background: We determined the relative efficacy of subcutaneous (SC) treprostinil in stable World Health Organization class II and III patients transitioned from IV epoprostenol.

Methods: This was an 8-week, multicenter, randomized study in which patients were transitioned from IV epoprostenol to SC treprostinil or placebo over a period of up to 14 days and monitored carefully during and after the transition period for signs of deterioration. Patients with clinical deterioration were returned promptly to epoprostenol. Placebo or SC treprostinil doses were titrated in response to symptoms. Time to adjudicated clinical deterioration was compared between treatment groups, and exercise capacity, symptoms of disease, and safety were assessed throughout the study.

Results: Twenty-two patients were enrolled and completed the study. Seven of 8 patients (88%) withdrawn to placebo had clinical deterioration, while only 1 of 14 patients (7%) withdrawn to SC treprostinil had clinical deterioration (p = 0.00023 based on a treatment comparison of time to deterioration). Analyses of exercise capacity and symptoms strongly supported the efficacy of SC treprostinil in epoprostenol-treated patients. Adverse events consisted of painful infusion site reactions and anticipated prostacyclin side effects.

Conclusions: SC treprostinil is effective in pulmonary arterial hypertension and prevents clinical deterioration and maintains functional status in patients transitioned from epoprostenol.

Key Words: prostacyclin • pulmonary hypertension • withdrawal trial

Related Editorial

Transition From IV to Subcutaneous Prostacyclin: Premature Withdrawal?

Shelley Shapiro and Nicholas S. Hill
Chest 2007 132: 741-743. [Full Text] [PDF]