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To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.

This study has been terminated.
(This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.)
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00430716
First received: January 31, 2007
Last updated: May 25, 2011
Last verified: May 2011
History of Changes
  Purpose

To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.


Condition Intervention Phase
Pulmonary Arterial Hypertension
 Drug: Sildenafil citrate
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multinational, Multicentre, Randomized, Parallel Group, Double-Blind Study To Assess The Efficacy and Safety Of 1 mg, 5 mg and 20 mg TID of Oral Sildenafil in the Treatment of Subjects Aged 18 Years and Over With Pulmonary Arterial Hypertension (PAH)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in the Total Distance Walked During 6MWT at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.


Secondary Outcome Measures:
  • Change From Baseline in mPAP at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    mPAP was measured using a pressure transducer positioned at the mid-axillary line.

  • Time to Clinical Worsening [ Time Frame: Baseline through Week 12 ] [ Designated as safety issue: No ]
    Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy.

  • Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    PAH Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).

  • Change From Baseline in BNP at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    BNP is a non-invasive biomarker and an indicator of progression of PAH/ RV dysfunction in participants with PAH.

  • Change From Baseline in Pro-BNP at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.

  • Change From Baseline in TAPSE Measurement at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    TAPSE was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH / RV dysfunction.

  • Change From Baseline in BORG Dyspnoea Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum] and 10 (maximum).


Enrollment: 130
Study Start Date: April 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sildenafil High dose Drug: Sildenafil citrate
oral, 20 mg, tid
Experimental: Sildenafil Low dose Drug: Sildenafil citrate
oral 1 mg, tid
Experimental: Sildenafil medium dose Drug: Sildenafil citrate
oral 5 mg, tid
Experimental: Sildenafil - Open label Phase
Open label extension from week 12 to week 24.
 Drug: Sildenafil citrate
oral 20 mg, tid

  Eligibility

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

Inclusion Criteria:

  • Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is >/= 100 m and </= 450 m.
  • Subjects with a mean pulmonary artery pressure of >/= 25 mmHg and a pulmonary artery wedge pressure of </= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization.

Exclusion Criteria:

  • Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis.
  • Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00430716

  Show 42 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00430716     History of Changes
Other Study ID Numbers: A1481244
Study First Received: January 31, 2007
Results First Received: April 22, 2011
Last Updated: May 25, 2011
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 19, 2013