Featured article
Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: The TReprostinil sodium Inhalation Used in the Management of Pulmonary arterial Hypertension (TRIUMPH) study open-label extension

https://doi.org/10.1016/j.healun.2011.08.019Get rights and content

Background

Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy.

Methods

A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH.

Results

Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 ± 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double-blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]).

Conclusions

Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months.

Section snippets

Materials and methods

Patients eligible for this open-label extension had previously completed the 12-week double-blind, placebo-controlled, TRIUMPH study.8 For patients that received the active drug for the first time during the open-label phase (ie, were randomly allocated to receive placebo in the double-blind phase), baseline data were those collected at their Week 12 double-blind visit. For patients who previously were randomized to receive the active drug in the double-blind phase, baseline data were those

Subject disposition

Results at 24 months are presented from 206 participants of the original 235 TRIUMPH patients. Of the 29 individuals who did not participate in the open-label phase, 23 (13 active, 10 placebo) discontinued before completing the double-blind phase,8 and 6 (5 active, 1 placebo) were not transitioned into the extension by the investigator. Baseline demographics, PAH etiology, and treatment history are summarized in Table 1. The 206 patients were a mean age of 54 ± 14 years, 167 (81%) were women,

Discussion

PAH remains an incurable disease, one marked by inevitable progression and eventually death. Despite improvements in 1-year survival on several monotherapy regimens or improvement in long-term clinical benefit, including chronic administration of inhaled iloprost,13 many patients continue to experience a high rate of comorbid events and an unacceptable 5-year mortality.1, 11, 12, 14, 15, 16 The only alternative to medical therapy and cure for PAH is lung transplantation. Unfortunately, both

Disclosure statement

The TRIUMPH study was funded by United Therapeutics Corporation, Research Triangle Park, North Carolina, and Lung Rx, LLC, Silver Spring, Maryland.

R. Benza has grant support and/or received honorarium from Actelion Pharmaceuticals, Gilead Sciences, Pfizer, United Therapeutics Corp, Lung Rx, Inc, Bayer Schering AG, and Novartis. W. Seeger received grant support and/or honorarium from Actelion Pharmaceuticals, Pfizer, United Therapeutics Corp, Lung Rx, Inc., and Bayer Schering AG. V. McLaughlin

References (33)

  • H.A. Ghofrani et al.

    Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension

    J Am Coll Cardiol

    (2003)
  • O. Sitbon et al.

    Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study

    Chest

    (2003)
  • M. Gomberg-Maitland et al.

    Compelling evidence of long-term outcomes in pulmonary arterial hypertension?A clinical perspective

    J Am Coll Cardiol

    (2011)
  • N. Galiè et al.

    Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial

    Lancet

    (2008)
  • R.L. Benza et al.

    Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL)

    Circulation

    (2010)
  • H. Wilkens et al.

    Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension

    Circulation

    (2001)
  • Cited by (88)

    • Pulmonary hypertension inhaled therapies: An updated review

      2023, American Journal of the Medical Sciences
    • Therapeutic approaches to improve pulmonary arterial load and right ventricular–pulmonary arterial coupling

      2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
    View all citing articles on Scopus
    View full text