Victor F Tapson1, Zhi-Cheng Jing2, Kai-Feng Xu3, Lei Pan4, Jeremy Feldman5, David G Kiely6, Eugene Kotlyar7, C Shane McSwain8, Kevin Laliberte8, Carl Arneson8, Lewis J Rubin9. 1. Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, NC. Electronic address: tapso001@mc.duke.edu. 2. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 3. Peking Union Medical College Hospital, Beijing, China. 4. Department of Pulmonary Vascular Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. 5. Arizona Pulmonary Specialists Ltd, Phoenix, AZ. 6. Cardiovascular Biomedical Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England; National Institutes of Health Research, and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England. 7. Heart Lung Clinic, St Vincent's Hospital, Sydney, NSW, Australia. 8. United Therapeutics Corporation, Research Triangle Park, NC. 9. UC San Diego Medical Center, San Diego, CA.
Abstract
BACKGROUND:Treprostinil is a stable prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine, a sustained-release oral formulation of treprostinil, was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe PAH. The objective of this study was to evaluate the efficacy and safety of oral treprostinil in patients with PAH receiving stable background endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I) therapy, or both. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study in 310 patients withPAH compared bid administration of oral treprostinil (n = 157) with placebo (n = 153). The primary end point was change in 6-min walk distance at week 16. Secondary efficacy end points were World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening. RESULTS:One hundred thirty-two patients (84%) receiving oral treprostinil and 138 (90%) receiving placebo completed the study. The mean ± SD dose of oral treprostinil at week 16 was 3.1 ± 1.9 mg bid. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% CI, -2 to 22 m; P = .089). There were no significant changes in secondary end points. The most common adverse events associated with oral treprostinil were headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%). CONCLUSIONS: The addition of oral treprostinil to background ERA and PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but tolerated by most subjects. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00887978; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND:Treprostinil is a stable prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine, a sustained-release oral formulation of treprostinil, was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe PAH. The objective of this study was to evaluate the efficacy and safety of oral treprostinil in patients with PAH receiving stable background endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I) therapy, or both. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study in 310 patients with PAH compared bid administration of oral treprostinil (n = 157) with placebo (n = 153). The primary end point was change in 6-min walk distance at week 16. Secondary efficacy end points were World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening. RESULTS: One hundred thirty-two patients (84%) receiving oral treprostinil and 138 (90%) receiving placebo completed the study. The mean ± SD dose of oral treprostinil at week 16 was 3.1 ± 1.9 mg bid. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% CI, -2 to 22 m; P = .089). There were no significant changes in secondary end points. The most common adverse events associated with oral treprostinil were headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%). CONCLUSIONS: The addition of oral treprostinil to background ERA and PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but tolerated by most subjects. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00887978; URL: www.clinicaltrials.gov.
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