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Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial.
Chest. 2013 Sep; 144(3):952-958.Chest

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 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.

Authors+Show Affiliations

Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, NC. Electronic address: tapso001@mc.duke.edu.Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.Peking Union Medical College Hospital, Beijing, China.Department of Pulmonary Vascular Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.Arizona Pulmonary Specialists Ltd, Phoenix, AZ.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.Heart Lung Clinic, St Vincent's Hospital, Sydney, NSW, Australia.United Therapeutics Corporation, Research Triangle Park, NC.United Therapeutics Corporation, Research Triangle Park, NC.United Therapeutics Corporation, Research Triangle Park, NC.UC San Diego Medical Center, San Diego, CA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23669822

Citation

Tapson, Victor F., et al. "Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (the FREEDOM-C2 Study): a Randomized Controlled Trial." Chest, vol. 144, no. 3, 2013, pp. 952-958.
Tapson VF, Jing ZC, Xu KF, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144(3):952-958.
Tapson, V. F., Jing, Z. C., Xu, K. F., Pan, L., Feldman, J., Kiely, D. G., Kotlyar, E., McSwain, C. S., Laliberte, K., Arneson, C., & Rubin, L. J. (2013). Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest, 144(3), 952-958. https://doi.org/10.1378/chest.12-2875
Tapson VF, et al. Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (the FREEDOM-C2 Study): a Randomized Controlled Trial. Chest. 2013;144(3):952-958. PubMed PMID: 23669822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. AU - Tapson,Victor F, AU - Jing,Zhi-Cheng, AU - Xu,Kai-Feng, AU - Pan,Lei, AU - Feldman,Jeremy, AU - Kiely,David G, AU - Kotlyar,Eugene, AU - McSwain,C Shane, AU - Laliberte,Kevin, AU - Arneson,Carl, AU - Rubin,Lewis J, AU - ,, PY - 2013/5/15/entrez PY - 2013/5/15/pubmed PY - 2014/1/8/medline SP - 952 EP - 958 JF - Chest JO - Chest VL - 144 IS - 3 N2 - 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. SN - 1931-3543 UR - https://www.unboundmedicine.com/medline/citation/23669822/Oral_treprostinil_for_the_treatment_of_pulmonary_arterial_hypertension_in_patients_receiving_background_endothelin_receptor_antagonist_and_phosphodiesterase_type_5_inhibitor_therapy__the_FREEDOM_C2_study_:_a_randomized_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-3692(13)60612-1 DB - PRIME DP - Unbound Medicine ER -