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

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ClinicalTrials.gov Identifier: NCT00430716
Recruitment Status : Terminated (This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.)
First Posted : February 2, 2007
Results First Posted : May 17, 2011
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

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

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Sildenafil citrate Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A MULTINATIONAL, MULTICENTRE, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND STUDY TO ASSESS THE EFFICACY AND SAFETY OF 1MG, 5MG AND 20 MG TID OF ORAL SILDENAFIL IN THE TREATMENT OF SUBJECTS AGED 18 YEARS AND OVER WITH PULMONARY ARTERIAL HYPERTENSION (PAH)
Actual Study Start Date : April 8, 2008
Actual Primary Completion Date : May 25, 2010
Actual Study Completion Date : May 25, 2010


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 [ Time Frame: Baseline and Week 12 ]
    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 :
  1. Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 [ Time Frame: Baseline and Week 12 ]
    mPAP was measured using a pressure transducer positioned at the mid-axillary line.

  2. Number of Participants With Clinical Worsening [ Time Frame: Baseline through Week 12 ]
    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. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.

  3. 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 ]
    Pulmonary arterial hypertension (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).

  4. Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 [ Time Frame: Baseline and Week 12 ]
    BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.

  5. Change From Baseline in Pro-BNP at Week 12 [ Time Frame: Baseline and Week 12 ]
    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.

  6. Change From Baseline in TAPSE Measurement at Week 12 [ Time Frame: Baseline and Week 12 ]

    Tricuspid annular plane systolic excursion (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 /right ventricular dysfunction.

    The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.


  7. Change From Baseline in BORG Dyspnoea Score at Week 12 [ Time Frame: Baseline and Week 12 ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00430716


Locations
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Sponsors and Collaborators
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
ClinicalTrials.gov Identifier: NCT00430716    
Other Study ID Numbers: A1481244
2006-006748-76 ( EudraCT Number )
First Posted: February 2, 2007    Key Record Dates
Results First Posted: May 17, 2011
Last Update Posted: December 22, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Citric Acid
Sodium Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents