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

BMC Pulmonary Medicine

Research Article

Zeenat Safdar¹  B. K. S. Sastry²  Carmine Dario Vizza³  Min Zhang⁴  Xiang Gao⁵  Manisha Lamba⁵  Lutz Harnisch⁶  Zhi-Cheng Jing⁷ 

[1] Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA;CARE Hospitals, Gandhi Bhavan Road Nampally, Hyderabad, India;Department of Cardiovascular and Respiratory Disease, University of Rome La Sapienza, Viale del Policlinico 155, 00161, Rome, Italy;Pfizer Inc, 10646 Science Center Dr, La Jolla Campus, 92121, San Diego, CA, USA;Pfizer Inc, 558 Eastern Point Rd, 06340, Groton, CT, USA;Pfizer Ltd, Ramsgate Road, CT13 9NJ, Sandwich Kent, UK;Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507, Zhengmin Road, Shanghai, China;

关键词: Sildenafil;    Clinical trial;    Pulmonary hypertension;    Exercise test;    Echocardiography;    Dose;   

DOI  :  10.1186/s12890-017-0374-x

 received in 2016-05-13, accepted in 2017-01-31,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsTreatment-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.ResultsThe 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.ConclusionsSildenafil 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 registrationClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007).

【 授权许可】

CC BY   
© The Author(s). 2017