PURPOSE: Intravenous prostacyclin (epoprostenol sodium) increases exercise capacity in idiopathic pulmonary arterial hypertension (IPAH) and scleroderma-associated PAH, and improves survival in IPAH. Treprostinil, a stable prostacyclin analogue, is approved for subcutaneous administration to diminish symptoms associated with exercise in World Health Organization (WHO) Class II-IV PAH. A placebo-controlled epoprostenol withdrawal trial in PAH would allow the evaluation of treprostinil in prostacyclin responders.The objective of this study was to evaluate the safety and efficacy of subcutaneous treprostinil in patients transitioned from intravenous epoprostenol.
METHODS: Patients were transitioned from intravenous epoprostenol to subcutaneous treprostinil or placebo over a period of up to 14 days and monitored carefully during and after the transition period for signs of deterioration. Those with clinical deterioration were quickly returned to epoprostenol. Study drug dose was adjusted to manage 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 Seven of 8 patients (93%) withdrawn to placebo deteriorated, while only 1 of 14 patients (14%) withdrawn to treprostinil had a clinical deterioration event (p = 0.00023 based on a treatment comparison of time to deterioration). Analyses of exercise capacity and symptoms strongly supported the efficacy of treprostinil in epoprostenol treated patients. Adverse events were consistent with the patient population and study design.
CONCLUSION: Treprostinil effectively treats PAH symptoms and prevents clinical deterioration in patients withdrawn from epoprostenol.
CLINICAL IMPLICATIONS: This study suggests that many patients may be effectively transitioned from epoprostenol to treprostinil and provides additional information regarding dosing strategy of such a transition.
DISCLOSURE: Robert Schilz, Grant monies (from industry related sources) Actelion, Cotherix, Encysive, Glaxo-Wellcome, ICOS, Myogen, Pfizer, United Therapeutics; Consultant fee, speaker bureau, advisory committee, etc. Actelion, Cotherix, Encysive, Glaxo-Wellcome, ICOS, Myogen, Pfizer, United Therapeutics.