دورية أكاديمية
Riociguat for the treatment of pulmonary arterial hypertension.
| العنوان: | Riociguat for the treatment of pulmonary arterial hypertension. |
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| المؤلفون: | Ghofrani HA; University of Giessen and Marburg Lung Center, Giessen, Germany. ardeschir.ghofrani@innere.med.uni-giessen.de, Galiè N, Grimminger F, Grünig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ |
| مؤلفون مشاركون: | PATENT-1 Study Group |
| المصدر: | The New England journal of medicine [N Engl J Med] 2013 Jul 25; Vol. 369 (4), pp. 330-40. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Boston, Massachusetts Medical Society. |
| مواضيع طبية MeSH: | Hypertension, Pulmonary/*drug therapy , Pyrazoles/*therapeutic use , Pyrimidines/*therapeutic use, Adult ; Aged ; Double-Blind Method ; Drug Administration Schedule ; Drug Therapy, Combination ; Endothelin Receptor Antagonists ; Exercise Tolerance/drug effects ; Female ; Humans ; Hypertension, Pulmonary/physiopathology ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Prostaglandins/therapeutic use ; Pyrazoles/administration & dosage ; Pyrazoles/adverse effects ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects ; Quality of Life ; Vascular Resistance/drug effects ; Walking |
| مستخلص: | Background: Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. Methods: In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety. Results: By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively). Conclusions: Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.). |
| التعليقات: | Comment in: N Engl J Med. 2013 Jul 25;369(4):386-8. (PMID: 23883383) Comment in: Nat Rev Cardiol. 2013 Oct;10(10):549. (PMID: 23939482) Comment in: N Engl J Med. 2013 Dec 5;369(23):2268. (PMID: 24304056) Comment in: N Engl J Med. 2013 Dec 5;369(23):2266. (PMID: 24304057) Comment in: N Engl J Med. 2013 Dec 5;369(23):2266-7. (PMID: 24304058) Comment in: N Engl J Med. 2013 Dec 5;369(23):2267. (PMID: 24304059) Comment in: N Engl J Med. 2013 Dec 5;369(23):2267. (PMID: 24304060) |
| فهرسة مساهمة: | Investigator: G Bortman; A Keogh; F Kermeen; J Feenstra; T Williams; G Reeves; D Kilpatrick; I Lang; C Kahler; R Mascherbauer-Steringer; JL Vachiery; M Delcroix; G Meyer; J Arakaki; M Santana; D Waetge; J Granton; D Langleben; D Helmersen; J He; Z Jing; D Zhou; Y Huang; C Wang; P Jansa; JE Neilsen-Kudsk; E Hachulla; P De Groote; I Frachon; A Bourdin; C Pison; F Bauer; C Dromer; CH Marquette; B Degano; C Neurohr; H Wilkens; G Hoffken; M Hoeper; A Ghofrani; H Wirtz; S Rosenkranz; E Grünig; R Ewert; S Orfanos; M Kramer; T Ben Gal; L Scelsi; C Vizza; S Harari; M Confalonieri; C Albera; Y Fukumoto; M Sano; M Hatano; T Saji; S Tanaka; Y Takeda; K Takehara; H Matsubara; Y Kihara; Y Shiohira; H Kawai; S Homma; T Satoh; T Tokunaga; T Ishizaki; C Diaz; T Zamudio; M De Los Rios; S Estupian; JR Cacho; M Gamba; L Beckert; A Torbicki; G Castro; A Reis; A Agapito; S Martins; H Kim; S Lee; H Chang; Y Song; I Chazova; O Moiseeva; S Lim; J Yip; J Barbera; A Roman; Jdel C Palma; O Reitan; S Soderberg; K Jansson; R Speich; HH Hsu; HY Lin; CC Cheng; A Phrommintikul; N Jaimchariyatam; T Sayin; H Kultursay; G Ongen; J Pepke-Zaba; G Coghlan; A Peacock; J Gibbs; L Wagoner; D Badesch; A Frost; N Hill; R Allen; A Waxman; N Sood; F Torres; O Minai; S Shapiro; J Klinger; P Engel; H Garcia; D Schuller; D Poch; E Rosenzweig; J McConnell; F Rischard; HA Ghofrani; N Galiè; F Grimminger; M Humbert; AM Keogh; D Langleben; LJ Rubin; H Olschewski; W Haverkamp; W Lehmacher; S Hoischen; S Collamati; J Dehay; M Hallmann; F Menezes |
| سلسلة جزيئية: | ClinicalTrials.gov NCT00810693; NCT00863681 |
| المشرفين على المادة: | 0 (Endothelin Receptor Antagonists) 0 (Peptide Fragments) 0 (Prostaglandins) 0 (Pyrazoles) 0 (Pyrimidines) 0 (pro-brain natriuretic peptide (1-76)) 114471-18-0 (Natriuretic Peptide, Brain) RU3FE2Y4XI (riociguat) |
| تواريخ الأحداث: | Date Created: 20130726 Date Completed: 20130802 Latest Revision: 20220408 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1056/NEJMoa1209655 |
| PMID: | 23883378 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1533-4406 |
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| DOI: | 10.1056/NEJMoa1209655 |