TY - JOUR
T1 - Efficacy of 1, 5, and 20mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension
T2 - A randomized, double-blind study with open-label extension
AU - Vizza, Carmine Dario
AU - Sastry, B. K.S.
AU - Safdar, Zeenat
AU - Harnisch, Lutz
AU - Gao, Xiang
AU - Zhang, Min
AU - Lamba, Manisha
AU - Jing, Zhi Cheng
N1 - Funding Information:
The authors would like to thank Susan Raber for assistance with the analyses presented in the manuscript. Editorial support was provided by Tiffany Brake, PhD, Candace Lundin, DVM, MS, and Janet E. Matsuura, PhD, from Complete Healthcare Communications, LLC, and was funded by Pfizer Inc.
Funding Information:
C.D.V. has received fees for serving as a speaker, consultant, and advisory board member from Actelion, Dompè, GlaxoSmithKline, Italfarmaco, Lilly, Pfizer, and United Therapeutics. B.K.S.S. has received research funding from Pfizer and Actelion. Z.S. has been a consultant and served as a speaker and advisory board member for United Therapeutics, Gilead, and Actelion. L.H., M.L., and M.Z. are Pfizer employees. X.G. is a former Pfizer employee. Z.-C.J. has received fees for serving as a speaker, consultant, and advisory board member from Actelion, Bayer, GlaxoSmithKline, Lilly, Pfizer, and United Therapeutics.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/2/23
Y1 - 2017/2/23
N2 - 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 80mg 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 12weeks of double-blind sildenafil 1, 5, or 20mg TID; 12weeks of open-label sildenafil 20mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5mg versus 20mg 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 1mg (P=0.011) but not versus 5mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1mg (74 vs 50 and 47m, 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 5mg. Conclusions: Sildenafil 20mg TID appeared to be more effective than 1mg TID for improving 6MWD; sildenafil 5mg TID appeared to have similar clinical and hemodynamic effects as 20mg TID. Trial registration: ClinicalTrials.gov NCT00430716(Registration date: January 31, 2007).
AB - 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 80mg 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 12weeks of double-blind sildenafil 1, 5, or 20mg TID; 12weeks of open-label sildenafil 20mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5mg versus 20mg 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 1mg (P=0.011) but not versus 5mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1mg (74 vs 50 and 47m, 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 5mg. Conclusions: Sildenafil 20mg TID appeared to be more effective than 1mg TID for improving 6MWD; sildenafil 5mg TID appeared to have similar clinical and hemodynamic effects as 20mg TID. Trial registration: ClinicalTrials.gov NCT00430716(Registration date: January 31, 2007).
KW - Clinical trial
KW - Dose
KW - Echocardiography
KW - Exercise test
KW - Pulmonary hypertension
KW - Sildenafil
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U2 - 10.1186/s12890-017-0374-x
DO - 10.1186/s12890-017-0374-x
M3 - Article
C2 - 28228114
AN - SCOPUS:85013816077
VL - 17
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
SN - 1471-2466
IS - 1
M1 - 44
ER -