A Study to Assess the Efficacy and Safety of 20, 40, and 80mg of Sildenafil Three Times a Day in the Treatment of Pulmonary Arterial Hypertension

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00644605
First received: March 20, 2008
Last updated: March 31, 2008
Last verified: March 2008
  Purpose

To evaluate the effect of three doses of oral sildenafil (20, 40 and 80 mg three times a day [TID]) on exercise capacity, as measured by the 6-Minute Walk test, as well as the safety and tolerability, after 12 weeks of treatment in subjects with pulmonary arterial hypertension who are aged 18 years and over. To investigate the plasma concentration-effect relationship and to determine the population pharmacokinetic (PK) parameters.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: sildenafil
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multinational, Multi-Centre, Randomised, Double-Blind, Double-Dummy, Placebo-Controlled Study to Assess the Efficacy and Safety of 20, 40, and 80mg TID Sildenafil in the Treatment of Pulmonary Arterial Hypertension in Subjects Aged 18 Years and Over

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test). [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in mean pulmonary arterial pressure [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Time from randomisation to the first occurrence of clinical worsening (death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy) [ Time Frame: Week 0 to 12 ] [ Designated as safety issue: No ]
  • Change from baseline in the BORG dyspnoea score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in the 8 dimensions of SF-36 (Physical functioning, Role functioning, Bodily pain, General health, Vitality, Social functioning, Mental health and Reported health transition) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
  • Patient overall preference assessment [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
  • Change from baseline in hemodynamic parameters [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 275
Study Start Date: October 2002
Study Completion Date: November 2003
Arms Assigned Interventions
Active Comparator: Arm 1 Drug: sildenafil
sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 2 Drug: sildenafil
sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 3 Drug: sildenafil
sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Placebo Comparator: Arm 4 Drug: placebo
placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Included patients had primary pulmonary arterial hypertension, pulmonary hypertension secondary to connective tissue disease, or pulmonary hypertension with surgical repair at least 5 years previously; a mean pulmonary artery pressure greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest, via right heart catheterisation within 21 days prior to randomisation; and a baseline 6-Minute Walk test distance of 100 m to 450 m.

Exclusion Criteria:

Subjects with congenital heart disease, pulmonary hypertension due to thromboembolism, HIV, chronic obstructive airway disease, congestive heart failure or schistosomiasis; subjects with significant (ie > 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation; and acutely decompensated heart failure within the previous 30 days; subjects with pulmonary hypertension secondary to any other etiology other than those specified in the inclusion criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00644605

  Show 68 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00644605     History of Changes
Other Study ID Numbers: A1481140
Study First Received: March 20, 2008
Last Updated: March 31, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Sildenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014