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Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension:A Double-Blind Placebo-controlled Clinical Trial
- Source :
- White, R J, Jerjes-Sanchez, C, Bohns Meyer, G M, Pulido, T, Sepulveda, P, Wang, K Y, Grünig, E, Hiremath, S, Yu, Z, Gangcheng, Z, Yip, W L J, Zhang, S, Khan, A, Deng, C Q, Grover, R, Tapson, V F & FREEDOM-EV 2020, ' Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension : A Double-Blind Placebo-controlled Clinical Trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC, American Journal of Respiratory and Critical Care Medicine, 201(6), 707-717. American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 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, De Souza, R, Meyer, G M B, Moreira, M C, Yoo, H, Lapa, M S, Swiston, J, Hirani, N, Mehta, S, Michelakis, E, Sepulveda, P, Zagolin, M, Liu, J, Zhang, S, Pan, L, Chunde, B, Qun, Y, Cheng, X, Yu, Z, Li, X, Hua, Y, Zhang, G, Zhu, X, Chen, Y, Cheng, Z, Yang, Y, Zhou, D, Shen, J, Nielsen-Kudsk, J E, Carlsen, J, Bourdin, A, Hachulla, E, Dromer, C, Chaouat, A, Reynaud-Gauber, M, Seronde, M F, Klose, H, Halank, M, Hoffken, G, Ewert, R, Rosenkranz, S, Grunig, E, Kruger, U, Kronsbein, J, Hauptmeier, B M, Koch, A, Held, M, Lange, T J, Neurohr, C, Wilkens, H, Wirtz, H, Konstantinides, S, Argyropoulou-Pataka, P, Orfanos, S, Hiremath, S, Kerkar, P G, Suresh, P V, Baxi, H A, Oomman, A, Abhaichand, R K, Edla Kumar, P K, Chopra, V, Mehrotra, R, Rajput, R K, Sawhney, J S, Bimalendu, S, Sharma, K H, Srinivasa Sastry, B K, Kramer, M R, Segel, M J, Ben-Dov, I, Berkman, N, Yigla, M, Adir, Y, D'Alto, M, Vizza, C D, Scelsi, L, Vitulo, P, Pulido, T R, Jerjes-Sanchez, C, Boonstra, A, Vonk, M C, Sobkowicz, B, Mularek-Kubzdela, T, Torbicki, A, Podolec, P, Teik, L S, Yip, W L J, Chang, H J, Kim, H K, Park, J B, Chang, S A, Kim, D K, Chung, W J, Song, J M, Nissell, M, Hjalmarsson, C, Rundqvist, B, Huang, W C, Cheng, C C, Hsu, C H, Hsu, H H, Wang, K Y, Coghlan, J G, Kiely, D G, Pepke-Zaba, J W, Lordan, J L, Corris, P A, Cadaret, L, Hansdottir, S, Oudiz, R J, Badesch, D B, Mathier, M, Schilz, R, Hill, N, Waxman, A, Markin, C J, Zwicke, D L, Fisher, M, Franco, V, Sood, N, Park, M H, Allen, R, Feldman, J P, Balasubramanian, V, Seeram, V K, Bajwa, A, Thompson, A B, Migliore, C, Elwing, J, McConnell, J W, Mehta, J P, Rahaghi, F F, Rame, J E, Khan, A, Patel, B, Oren, R M, Klinger, J R, Alnuaimat, H, Allen, S, Harvey, W, Eggert, M S, Hage, A, Miller, C E, Awdish, R, Cajigas, H, Grinnan, D, Trichon, B H, McDonough, C, White, R J & Rischard, F 2020, ' Combination therapy with oral treprostinil for pulmonary arterial hypertension : A double-blind placebo-controlled clinical trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC, American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2020, 201 (6), pp.707-717. ⟨10.1164/rccm.201908-1640OC⟩, White, R J, Jerjes-Sanchez, C, Bohns Meyer, G M, Pulido, T, Sepulveda, P, Wang, K Y, Grünig, E, Hiremath, S, Yu, Z, Gangcheng, Z, Yip, W L J, Zhang, S, Khan, A, Deng, C Q, Grover, R, Tapson, V F, FREEDOM-EV Investigators, Svetliza, G N, Lescano, A J, Bortman, G R, Carlsen, J, McDonough, C, White, J R & Rischard, F 2020, ' Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension : A Double-Blind Placebo-controlled Clinical Trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC
- Publication Year :
- 2020
-
Abstract
- Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud 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.\ud \ud 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.\ud \ud 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.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).
- Subjects :
- Male
Administration, Oral
Oral treprostinil
Critical Care and Intensive Care Medicine
Pulmonary arterial hypertension
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
combination therapy
oral
epoprostenol
0302 clinical medicine
pulmonary arterial hypertension
middle aged
Clinical endpoint
double-blind method
MESH: Double-Blind Method
Familial Primary Pulmonary Hypertension
030212 general & internal medicine
humans
MESH: Aged
MESH: Middle Aged
Epoprostenol/analogs & derivatives
adult
Hazard ratio
Middle Aged
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
antihypertensive agents
3. Good health
aged
female
MESH: Young Adult
oral treprostinil
MESH: Administration, Oral
young adult
Female
Pulmonary Arterial Hypertension/drug therapy
medicine.drug
Adult
Pulmonary and Respiratory Medicine
MESH: Pulmonary Arterial Hypertension
medicine.medical_specialty
Randomization
Adolescent
clinical study
sequential therapy
administration, oral
adolescent
male
placebos
Sequential therapy
MESH: Placebos
MESH: Epoprostenol
Lower risk
Placebo
administration
Clinical study
Young Adult
03 medical and health sciences
Double-Blind Method
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Internal medicine
medicine
Humans
Combination therapy
Adverse effect
Placebos/therapeutic use
Aged
MESH: Adolescent
Pulmonary Vascular Disease
MESH: Antihypertensive Agents
MESH: Humans
business.industry
MESH: Adult
Original Articles
MESH: Male
Clinical trial
030228 respiratory system
Antihypertensive Agents/administration & dosage
business
MESH: Female
Treprostinil
Subjects
Details
- Language :
- English
- ISSN :
- 1073449X and 15354970
- Database :
- OpenAIRE
- Journal :
- White, R J, Jerjes-Sanchez, C, Bohns Meyer, G M, Pulido, T, Sepulveda, P, Wang, K Y, Grünig, E, Hiremath, S, Yu, Z, Gangcheng, Z, Yip, W L J, Zhang, S, Khan, A, Deng, C Q, Grover, R, Tapson, V F & FREEDOM-EV 2020, ' Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension : A Double-Blind Placebo-controlled Clinical Trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC, American Journal of Respiratory and Critical Care Medicine, 201(6), 707-717. American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 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, De Souza, R, Meyer, G M B, Moreira, M C, Yoo, H, Lapa, M S, Swiston, J, Hirani, N, Mehta, S, Michelakis, E, Sepulveda, P, Zagolin, M, Liu, J, Zhang, S, Pan, L, Chunde, B, Qun, Y, Cheng, X, Yu, Z, Li, X, Hua, Y, Zhang, G, Zhu, X, Chen, Y, Cheng, Z, Yang, Y, Zhou, D, Shen, J, Nielsen-Kudsk, J E, Carlsen, J, Bourdin, A, Hachulla, E, Dromer, C, Chaouat, A, Reynaud-Gauber, M, Seronde, M F, Klose, H, Halank, M, Hoffken, G, Ewert, R, Rosenkranz, S, Grunig, E, Kruger, U, Kronsbein, J, Hauptmeier, B M, Koch, A, Held, M, Lange, T J, Neurohr, C, Wilkens, H, Wirtz, H, Konstantinides, S, Argyropoulou-Pataka, P, Orfanos, S, Hiremath, S, Kerkar, P G, Suresh, P V, Baxi, H A, Oomman, A, Abhaichand, R K, Edla Kumar, P K, Chopra, V, Mehrotra, R, Rajput, R K, Sawhney, J S, Bimalendu, S, Sharma, K H, Srinivasa Sastry, B K, Kramer, M R, Segel, M J, Ben-Dov, I, Berkman, N, Yigla, M, Adir, Y, D'Alto, M, Vizza, C D, Scelsi, L, Vitulo, P, Pulido, T R, Jerjes-Sanchez, C, Boonstra, A, Vonk, M C, Sobkowicz, B, Mularek-Kubzdela, T, Torbicki, A, Podolec, P, Teik, L S, Yip, W L J, Chang, H J, Kim, H K, Park, J B, Chang, S A, Kim, D K, Chung, W J, Song, J M, Nissell, M, Hjalmarsson, C, Rundqvist, B, Huang, W C, Cheng, C C, Hsu, C H, Hsu, H H, Wang, K Y, Coghlan, J G, Kiely, D G, Pepke-Zaba, J W, Lordan, J L, Corris, P A, Cadaret, L, Hansdottir, S, Oudiz, R J, Badesch, D B, Mathier, M, Schilz, R, Hill, N, Waxman, A, Markin, C J, Zwicke, D L, Fisher, M, Franco, V, Sood, N, Park, M H, Allen, R, Feldman, J P, Balasubramanian, V, Seeram, V K, Bajwa, A, Thompson, A B, Migliore, C, Elwing, J, McConnell, J W, Mehta, J P, Rahaghi, F F, Rame, J E, Khan, A, Patel, B, Oren, R M, Klinger, J R, Alnuaimat, H, Allen, S, Harvey, W, Eggert, M S, Hage, A, Miller, C E, Awdish, R, Cajigas, H, Grinnan, D, Trichon, B H, McDonough, C, White, R J & Rischard, F 2020, ' Combination therapy with oral treprostinil for pulmonary arterial hypertension : A double-blind placebo-controlled clinical trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC, American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2020, 201 (6), pp.707-717. ⟨10.1164/rccm.201908-1640OC⟩, White, R J, Jerjes-Sanchez, C, Bohns Meyer, G M, Pulido, T, Sepulveda, P, Wang, K Y, Grünig, E, Hiremath, S, Yu, Z, Gangcheng, Z, Yip, W L J, Zhang, S, Khan, A, Deng, C Q, Grover, R, Tapson, V F, FREEDOM-EV Investigators, Svetliza, G N, Lescano, A J, Bortman, G R, Carlsen, J, McDonough, C, White, J R & Rischard, F 2020, ' Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension : A Double-Blind Placebo-controlled Clinical Trial ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 6, pp. 707-717 . https://doi.org/10.1164/rccm.201908-1640OC
- Accession number :
- edsair.doi.dedup.....247f9389052b9bd4d58d6383633fc9da