Victor F Tapson1, Fernando Torres2, Fiona Kermeen3, Anne M Keogh4, Roblee P Allen5, Robert P Frantz6, David B Badesch7, Adaani E Frost8, Shelley M Shapiro9, Kevin Laliberte10, Jeffrey Sigman10, Carl Arneson10, Nazzareno Galiè11. 1. Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, NC. Electronic address: victor.tapson@dm.duke.edu. 2. Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 3. Prince Charles Hospital, Brisbane, QLD, Australia. 4. St. Vincent's Hospital, Sydney, NSW, Australia. 5. UC Davis Medical Center, Sacramento, CA. 6. Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN. 7. Divisions of Pulmonary Sciences and Critical Care Medicine and Cardiology, University of Colorado Denver, Denver, CO. 8. Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX. 9. West Los Angeles Veterans Administration Healthcare Center, Los Angeles, CA. 10. United Therapeutics Corporation, Research Triangle Park, NC. 11. Department of Medicine, Institute of Cardiology, Bologna, Italy.
Abstract
BACKGROUND: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized toplacebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score. RESULTS: Thirty-nine patients (22%) receiving oral treprostiniland 24 patients (14%) receiving placebo discontinued the study. Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 m (P = .07). Improvements in dyspnea fatigue index score (P = .01) and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid dose of < 1 mg or discontinued because of adverse events (4 m). CONCLUSIONS: The primary end point of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing, which has set the stage for additional studies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score. RESULTS: Thirty-nine patients (22%) receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued the study. Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 m (P = .07). Improvements in dyspnea fatigue index score (P = .01) and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid dose of &lt; 1 mg or discontinued because of adverse events (4 m). CONCLUSIONS: The primary end point of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing, which has set the stage for additional studies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov.
Authors: Rennie L Rhee; Nicole B Gabler; Sapna Sangani; Amy Praestgaard; Peter A Merkel; Steven M Kawut Journal: Am J Respir Crit Care Med Date: 2015-11-01 Impact factor: 21.405
Authors: Lori Dwyer-Nield; Gregory A Hickey; Micah Friedman; Kevin Choo; Debbie G McArthur; Meredith A Tennis; Melissa L New; Mark Geraci; Robert L Keith Journal: Cancer Prev Res (Phila) Date: 2017-08-29