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Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension

BACKGROUND: In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. METHODS: Treatment-naive pa...

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Autores principales: Vizza, Carmine Dario, Sastry, B. K. S., Safdar, Zeenat, Harnisch, Lutz, Gao, Xiang, Zhang, Min, Lamba, Manisha, Jing, Zhi-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322647/
https://www.ncbi.nlm.nih.gov/pubmed/28228114
http://dx.doi.org/10.1186/s12890-017-0374-x
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author Vizza, Carmine Dario
Sastry, B. K. S.
Safdar, Zeenat
Harnisch, Lutz
Gao, Xiang
Zhang, Min
Lamba, Manisha
Jing, Zhi-Cheng
author_facet Vizza, Carmine Dario
Sastry, B. K. S.
Safdar, Zeenat
Harnisch, Lutz
Gao, Xiang
Zhang, Min
Lamba, Manisha
Jing, Zhi-Cheng
author_sort Vizza, Carmine Dario
collection PubMed
description BACKGROUND: In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, functional class, and biomarkers were assessed. RESULTS: The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated. At week 12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and 47 m, respectively). At week 12, changes in hemodynamic parameters were generally small and variable between treatment groups; odds ratios for improvement in functional class were not statistically significantly different. Improvements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg. CONCLUSIONS: Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID. TRIAL REGISTRATION: ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-017-0374-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-53226472017-03-01 Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension Vizza, Carmine Dario Sastry, B. K. S. Safdar, Zeenat Harnisch, Lutz Gao, Xiang Zhang, Min Lamba, Manisha Jing, Zhi-Cheng BMC Pulm Med Research Article BACKGROUND: In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. METHODS: Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, functional class, and biomarkers were assessed. RESULTS: The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated. At week 12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and 47 m, respectively). At week 12, changes in hemodynamic parameters were generally small and variable between treatment groups; odds ratios for improvement in functional class were not statistically significantly different. Improvements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg. CONCLUSIONS: Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID. TRIAL REGISTRATION: ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-017-0374-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-23 /pmc/articles/PMC5322647/ /pubmed/28228114 http://dx.doi.org/10.1186/s12890-017-0374-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Vizza, Carmine Dario
Sastry, B. K. S.
Safdar, Zeenat
Harnisch, Lutz
Gao, Xiang
Zhang, Min
Lamba, Manisha
Jing, Zhi-Cheng
Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title_full Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title_fullStr Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title_full_unstemmed Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title_short Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
title_sort efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322647/
https://www.ncbi.nlm.nih.gov/pubmed/28228114
http://dx.doi.org/10.1186/s12890-017-0374-x
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