| Authors: |
White, R. James; Jerjes-Sanchez, Carlos; Meyer, Gisela Martina Bohns; Pulido, Tomas; Sepulveda, Pablo; Wang, Kuo Yang; Grünig, Ekkehard; Hiremath, Shirish; Yu, Zaixin; Zhang, Gangcheng; Yip, Wei Luen James; Zhang, Shuyang; Khan, Akram; Deng, C. Q.; Grover, Rob; Tapson, Victor F.; Svetliza, Graciela Noemi; Lescano, Adrian Jose; Bortman, Guillermo Roberto; Diez, Fabian Antonio; Botta, Christian Edgardo; Fitzgerald, John; Feenstra, Eelke; Kermeen, Fiona Dawn; Keogh, Anne Margaret; Williams, Trevor John; Yousseff, Peter Paul; Ng, Benjamin Joh Han; Smallwood, David Mc Naughton; Dwyer, Nathan Brent; Brown, Martin Russell; Lang, Irene M.; Steringer-Mascherbauer, Regina; Arakaki, Jaquelina Ota; Campos, Frederico; De Amorim Correa, Ricardo; De Souza, Rogerio; Moreira, Maria Carmo; Yoo, Hugo; Lapa, Monica Silveira; Swiston, John; Hirani, Naushad; Mehta, Sanjay; Michelakis, Evangelos; Zagolin, Monica; Liu, Jimming; Pan, Lei; Chunde, Bao; Qun, Yi; Cheng, Xiaoshu; Li, Xinli; Hua, Yao; Zhu, Xianyang; Chen, Yundai; Cheng, Zhaozhong; Yang, Yuanhua; Zhou, Daxin; Shen, Jieyan; Nielsen-Kudsk, Jens Erik; Carlsen, Jorn; Bourdin, Arnaud; Hachulla, Eric; Dromer, Claire; Chaouat, Ari; Reynaud-Gauber, Martine; Seronde, Marie France; Klose, Hans; Halank, Michael; Hoffken, Gert; Ewert, Ralf; Rosenkranz, Stephan; Grunig, Ekkehard; Kruger, Ulrich; Kronsbein, Juliane; Hauptmeier, Barbara Monika; Koch, Andrea; Held, Matthias; Lange, Tobias Johannes; Neurohr, Claus; Wilkens, Heinrike; Wirtz, Hubert; Konstantinides, Stavros; Argyropoulou-Pataka, Paraskevi; Orfanos, Stylianos; Kerkar, Prafulla Gopinath; Suresh, Pujar Venkateshacharya; Baxi, Hemang Ashwinkumar; Oomman, Abraham; Abhaichand, Rajpal Kanaklal; Edla Kumar, P. K.; Chopra, Vijay; Mehrotra, Rahul; Rajput, Rajeev Kumar; Sawhney, Jitendra Singh; Bimalendu, Subir; Sharma, Kamal Harishchandra; Srinivasa Sastry, B. K.; Kramer, Mordechai Reuben; Segel, Michael Jonathan; Ben-Dov, Issahar; Berkman, Neville; Yigla, Mordechai; Adir, Yochai; D'Alto, Michael; Vizza, Carmine Dario; Scelsi, Laura; Vitulo, Patrizio; Pulido, Tomas Rene; Boonstra, Anko; Vonk, Madelon Clementina; Sobkowicz, Bozena; Mularek-Kubzdela, Tatiana; Torbicki, Adam; Podolec, Piotr; Teik, Lim Soo; Chang, Hyuk Jae; Kim, Hyung Kwan; Park, Jun Bean; Chang, Sung A.; Kim, Duk Kyung; Chung, Wook Jin; Song, Jong Min; Nissell, Magnus; Hjalmarsson, Clara; Rundqvist, Bengt; Huang, Wei Chun; Cheng, Chin Chang; Hsu, Chih Hsin; Hsu, Hsao Hsun; Coghlan, John Gerard; Kiely, David Gerard; Pepke-Zaba, Joanna Wanda; Lordan, James Lawrence; Corris, Paul Anthony; Cadaret, Linda; Hansdottir, Sif; Oudiz, Ronald Jack; Badesch, David B.; Mathier, Michael; Schilz, Robert; Hill, Nicholas; Waxman, Aaron; Markin, Catherine J.; Zwicke, Diane Lynn; Fisher, Micah; Franco, Veronica; Sood, Namita; Park, Myung H.; Allen, Roblee; Feldman, Jeremy P.; Balasubramanian, Vijay; Seeram, Vandana Kavita; Bajwa, Abubakr; Thompson, Austin B.; Migliore, Christina; Elwing, Jean; McConnell, John W.; Mehta, Jinesh P.; Rahaghi, Franck Farzad; Rame, J. Eduardo; Patel, Bela; Oren, Ron M.; Klinger, James R.; Alnuaimat, Hassan; Allen, Samuel; Harvey, William; Eggert, Michael S.; Hage, Antoine; Miller, Chad E.; Awdish, Rana; Cajigas, Hector; Grinnan, Daniel; Trichon, Benjamin Howard; McDonough, Clark; Rischard, Franz |
| Source: |
White, R J, Jerjes-Sanchez, C, Meyer, G M B, Pulido, T, Sepulveda, P, Wang, K Y, Grünig, E, Hiremath, S, Yu, Z, Zhang, G, Yip, W L J, Zhang, S, Khan, A, Deng, C Q, Grover, R, Tapson, V F, Svetliza, G N, Lescano, A J, Bortman, G R, Diez, F A, Botta, C E, Fitzgerald, J, Feenstra, E, Kermeen, F D, Keogh, A M, Williams, T J, Yousseff, P P, Ng, B J H, Smallwood, D M N, Dwyer, N B, Brown, M R, Lang, I M, Steringer-Mascherbauer, R, Arakaki, J O, Campos, F, De Amorim Correa, R, .... |
| Description: |
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. |