{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:38:12Z","timestamp":1791074292929,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,2,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH, but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue treprostinil diolamine as initial treatment for de novo PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Three hundred forty-nine patients (intent-to-treat population) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified intent-to-treat) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25-mg treprostinil tablets at randomization. The primary end point was change from baseline in 6-minute walk distance at week 12. Secondary end points included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6-minute walk distance (modified intent-to-treat population) was 23.0 m (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0125). For the intent-to-treat population, 6-minute walk distance improvements were observed at peak (26.0 m;\n                      <jats:italic>P<\/jats:italic>\n                      =0.0001) and trough (17.0 m;\n                      <jats:italic>P<\/jats:italic>\n                      =0.0025) plasma study drug concentrations. Other than an improvement in the combined 6-minute walk distance\/Borg dyspnea score, there were no significant changes in secondary end points. Oral treprostinil therapy was generally well tolerated; the most common adverse events (intent-to-treat) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:\u2014<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"NCT00325403\">NCT00325403<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.112.124388","type":"journal-article","created":{"date-parts":[[2013,1,11]],"date-time":"2013-01-11T02:02:00Z","timestamp":1357869720000},"page":"624-633","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":288,"title":["Efficacy and Safety of Oral Treprostinil Monotherapy for the Treatment of Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"127","author":[{"given":"Zhi-Cheng","family":"Jing","sequence":"first","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyur","family":"Parikh","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Pulido","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Jerjes-Sanchez","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. James","family":"White","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roblee","family":"Allen","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Torbicki","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yehle","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Laliberte","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Arneson","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis J.","family":"Rubin","sequence":"additional","affiliation":[{"name":"From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China (Z.-C.J.); Care Institute of Medical Science, Ahmedabad, India (K.P.); Instituto Nacional de Cardiologia, Mexico City, Mexico (T.P.); Unidad de Investigacion Clinica en Medicina, Monterrey, Mexico (C.J.-S.); University of Rochester Medical Center, Rochester, NY (R.J.W.); UC Davis Medical Center, Sacramento, CA (R.A.); Medical Center of Postgraduate Education, ECZ \u2013 Otwock, Poland (A.T.); Peking Union Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.01.004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040291"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.2.4695"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.029"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.66.2.334"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340504"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.6.2106079"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.036"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/112972980600700304"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2009.09.005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S19281"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.2.9810008"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020204"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.05.070"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200603-358OC"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.01.027"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2011.08.019"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01786-2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00463-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200302000-00019"},{"key":"e_1_3_4_22_2","volume-title":"Tyvaso (treprostinil) inhalation solution [US Food and Drug Administration drug product label]","year":"2011","unstructured":"Tyvaso (treprostinil) inhalation solution [US Food and Drug Administration drug product label]. 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