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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007).
authors.affiliation: Department of Cardiovascular and Respiratory Disease, University of Rome La Sapienza, Viale del Policlinico 155, 00161, Rome, Italy. dario.vizza@gmail.com.
authors.forename: Carmine Dario
authors.identifier: 0000-0002-3540-4983
authors.initials: CD
authors.lastname: Vizza
authors.affiliation: CARE Hospitals, Gandhi Bhavan Road Nampally, Hyderabad, India.
authors.forename: B K S
authors.initials: BK
authors.lastname: Sastry
authors.affiliation: Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Safdar
authors.affiliation: Pfizer Ltd, Ramsgate Road, Sandwich Kent, CT13 9NJ, UK.
authors.forename: Lutz
authors.initials: L
authors.lastname: Harnisch
authors.affiliation: Pfizer Inc, 558 Eastern Point Rd, Groton, CT, 06340, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Pfizer Inc, 10646 Science Center Dr, La Jolla Campus, San Diego, CA, 92121, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Pfizer Inc, 558 Eastern Point Rd, Groton, CT, 06340, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Lamba
authors.affiliation: Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507, Zhengmin Road, Shanghai, China.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000070857:Walk Test; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D000068677:Sildenafil Citrate
keywords: Clinical trial; Dose; Echocardiography; Exercise test; Pulmonary hypertension; Sildenafil