Evaluate The Clinical Effectiveness, Safety And Tolerability Of Sildenafil Used In Doses ≥20mg TID For The Treatment Of Pulmonary Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT01365585
• Recruitment Status: Completed
• First Posted: June 3, 2011
• Results First Posted: October 31, 2012
• Last Update Posted: February 1, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Study Description

Brief Summary:

The objective of this observational study is to gain clinical insight on the actual use of sildenafil citrate (Revatio™) for the treatment of pulmonary arterial hypertension (PAH). The primary objective is to assess effectiveness and safety of sildenafil at doses ≥20mg three times daily for the treatment of PAH.

Condition or disease	Intervention/treatment
Pulmonary Arterial Hypertension	Drug: sildenafil citrate

Detailed Description:

The study design proposed is a retrospective chart review going back five years (01 April 2006 estimate) from the time of study initiation (31 March 2011 estimate). Within this five-year period, study index will occur the first time an adult patient begins sildenafil for the treatment of PAH for a period of at least three months. The patient has to be taking sildenafil at doses ≥ 20mg tid for the treatment of PAH.

Study Design

• Study Type: Observational
• Actual Enrollment: 227 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Evaluate The Clinical Effectiveness, Safety And Tolerability Of Sildenafil Used In Doses ≥20mg TID For The Treatment Of Pulmonary Arterial Hypertension
• Study Start Date: July 2011
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: October 2011

Groups and Cohorts

Group/Cohort	Intervention/treatment
Sildenafil ≥20mg three times daily; Subjects receiving sildenafil ≥20mg three times daily for the treatment of PAH	Drug: sildenafil citrate; Sildenafil citrate, 20mg oral tablets, taken at least three times daily

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 1 [ Time Frame: Baseline, Year 1 ]
   6MWD 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.
2. Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 2 [ Time Frame: Baseline, Year 2 ]
   6MWD 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.
3. Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 3 [ Time Frame: Baseline, Year 3 ]
   6MWD 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.
4. Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 4 [ Time Frame: Baseline, Year 4 ]
   6MWD 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.

Secondary Outcome Measures :

1. Change From Baseline in New York Heart Association, World Health Organization (NYHA/WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   NYHA/WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (can not perform a physical activity without any symptoms, dyspnea at rest). Improvement=reduction in functional class, deterioration = increase in functional class, no change = no change in functional class. Number of participants in each functional class was reported.
2. Change From Baseline in Right Atrial Pressure (RAP) at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   RAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
3. Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Rest at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   mPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.
4. Change From Baseline in Pulmonary Vascular Resistance (PVR) at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).
5. Change From Baseline in Cardiac Index (CI) at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   CI: calculated as COsys divided by BSA.
6. Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
7. Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4 [ Time Frame: Baseline, Year 1, 2, 3, 4 ]
   Borg dyspnea scale: 10-point scale where following scores stands for severity of dyspnea: 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; 7=very severe breathlessness; 9=very very severe (almost maximum) and 10=maximum.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients at least 18 years of age diagnosed with pulmonary arterial hypertension (PAH; per Dana Point classification) and treated with sildenafil citrate for their PAH

Criteria

Inclusion Criteria:

• Patients must be at least 18 years of age at study index;
• Patients must have a diagnosis of PAH. PAH is conventionally defined as a mean pulmonary arterial pressure (PAP) of > 25 mmHg and a pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) ≥ 240 dynes/s/cm-5 at right heart catheterization;
• Patients must have initiated sildenafil for the treatment of their PAH; at dose ≥ 20 mg tid within 5 years prior to study initiation

Exclusion Criteria:

• Patient has known contraindications to sildenafil at study index;
• Patient participated in an investigational study of sildenafil treatment for PAH during the period beginning 6 months prior to study index

Contacts and Locations

Locations

Germany

Medizinische Hochschule Hannover

Hannover, Germany, 30625

Ireland

Mater Misericordiae Hospital

Dublin, Ireland, 7

Sponsors and Collaborators

Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01365585
• Other Study ID Numbers: A1481297
• First Posted: June 3, 2011
• Results First Posted: October 31, 2012
• Last Update Posted: February 1, 2021
• Last Verified: January 2021

Keywords provided by Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. ):

Pulmonary arterial hypertension; sildenafil citrate; Revatio

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Sildenafil Citrate; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Urological Agents