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 Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.


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).

Keywords: Clinical trial; Dose; Echocardiography; Exercise test; Pulmonary hypertension; Sildenafil.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Echocardiography
  • Female
  • Hemodynamics*
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • International Cooperation
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Severity of Illness Index
  • Sildenafil Citrate / administration & dosage
  • Sildenafil Citrate / therapeutic use*
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / therapeutic use*
  • Walk Test
  • Young Adult


  • Vasodilator Agents
  • Natriuretic Peptide, Brain
  • Sildenafil Citrate

Associated data

  • ClinicalTrials.gov/NCT00430716
  • ClinicalTrials.gov/NCT00430716