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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01365585

Enrollment

227

Registered

2011-06-03

Start date

2011-07-31

Completion date

2011-10-31

Last updated

2021-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension, sildenafil citrate, Revatio

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.

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.

Interventions

DRUGsildenafil citrate

Sildenafil citrate, 20mg oral tablets, taken at least three times daily

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 1	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.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 2	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.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 3	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.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 4	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

Measure	Time frame	Description
Change From Baseline in Cardiac Index (CI) at Year 1, 2, 3 and 4	Baseline, Year 1, 2, 3, 4	CI: calculated as COsys divided by BSA.
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	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.
Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 4	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.
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Year 1, 2, 3 and 4	Baseline, Year 1, 2, 3, 4	PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
Change From Baseline in Right Atrial Pressure (RAP) at Year 1, 2, 3 and 4	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.
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Rest at Year 1, 2, 3 and 4	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.
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Year 1, 2, 3 and 4	Baseline, Year 1, 2, 3, 4	PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).

Countries

Germany, Ireland

Participant flow

Participants by arm

Arm	Count
Sildenafil Participants who received sildenafil greater than or equal to 20 milligram (mg) three times daily as per Summary of Product Characteristics (SmPC) for the treatment of pulmonary arterial hypertension (PAH) for a period of at least 3 months, were observed retrospectively for 5 years.	227
Total	227

Baseline characteristics

Characteristic	Sildenafil
Age, Continuous	60.5 years STANDARD_DEVIATION 14.37
Borg Dyspnea Index	3.7 units on a scale STANDARD_DEVIATION 1.91
Cardiac Index (CI)	2.5 (Liter/minute)/square meter([L/min]/m^2) STANDARD_DEVIATION 1.51
Mean Pulmonary Arterial Pressure (mPAP) at rest	44.8 mmHg STANDARD_DEVIATION 12.37
New York Heart Association, World Health Organization (NYHA/WHO) Functional Class Class I	1 participants
New York Heart Association, World Health Organization (NYHA/WHO) Functional Class Class II	39 participants
New York Heart Association, World Health Organization (NYHA/WHO) Functional Class Class III	163 participants
New York Heart Association, World Health Organization (NYHA/WHO) Functional Class Class IV	13 participants
Pulmonary Capillary Wedge Pressure (PCWP)	7.6 mmHg STANDARD_DEVIATION 3.84
Pulmonary Vascular Resistance (PVR)	612.8 dynes*second/centimeter^5 STANDARD_DEVIATION 250.54
Right Atrial Pressure (RAP)	6.6 millimeters of mercury (mmHg) STANDARD_DEVIATION 4.85
Sex/Gender, Customized Female	145 participants
Sex/Gender, Customized Male	81 participants
Six-Minute Walk Distance (6MWD)	331.7 meter STANDARD_DEVIATION 117.42

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	11 / 227
serious Total, serious adverse events	0 / 227

Outcome results

Primary

Change From Baseline in 6-Minute Walk Distance (6MWD) at 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.

Time frame: Baseline, Year 1

Arm	Measure	Value (MEAN)	Dispersion
Sildenafil	Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 1	29.4 meter	Standard Deviation 81.38

Primary

Change From Baseline in 6-Minute Walk Distance (6MWD) at 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.

Time frame: Baseline, Year 2

Arm	Measure	Value (MEAN)	Dispersion
Sildenafil	Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 2	20.8 meter	Standard Deviation 83.82

Primary

Change From Baseline in 6-Minute Walk Distance (6MWD) at 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.

Time frame: Baseline, Year 3

Arm	Measure	Value (MEAN)	Dispersion
Sildenafil	Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 3	8.7 meter	Standard Deviation 73.82

Primary

Change From Baseline in 6-Minute Walk Distance (6MWD) at 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.

Time frame: Baseline, Year 4

Arm	Measure	Value (MEAN)	Dispersion
Sildenafil	Change From Baseline in 6-Minute Walk Distance (6MWD) at Year 4	-50.2 meter	Standard Deviation 86.24

Secondary

Change From Baseline in Borg Dyspnea Index at Year 1, 2, 3 and 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.