The VISION Trial: Ventavis Inhalation With Sildenafil to Improve and Optimize Pulmonary Arterial Hypertension

Study Overview
=================
Brief Summary
-----------------
The purpose of this multi-center international trial is to evaluate the safety and effectiveness of adding iloprost or placebo (an inactive substance that contains no active study drug) to sildenafil therapy for pulmonary arterial hypertension (PAH). The study will also examine whether patients on sildenafil can reduce the number of iloprost inhalations from the approved 6 doses per day to 4 doses per day.

Official Title
-----------------
A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of the Addition of Inhaled Iloprost in Patients With Pulmonary Arterial Hypertension Receiving Oral Sildenafil

Conditions
-----------------
Pulmonary Hypertension

Intervention / Treatment
-----------------
* Drug: Inhaled Iloprost (5 μg)
* Drug: Inhaled Placebo
* Drug: Sildenafil
* Drug: Bosentan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 12-85 years; of either gender. Confirmed PAH due to idiopathic pulmonary arterial hypertension (IPAH) or familial pulmonary arterial hypertension (FPAH). 6-minute walk distance (6-MWD) between 100-450 meters at screening. On a stable dose of sildenafil, with or without bosentan. Exclusion Criteria: Any treatment for PAH with prostacyclins, prostacyclin analogues, endothelin-1 antagonists, or phosphodiesterase-5 (PDE-5) inhibitors other than sildenafil within the past 12 weeks. Pulmonary hypertension due to conditions other than those stated in inclusion criteria. Additional PAH medications added within the past 12 weeks.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DB inhaled iloprost 6x/day<br>inhaled iloprost (5 μg) 6 times per day (6×/day) plus sildenafil with or without bosentan during the double blind period | Drug: Inhaled Iloprost (5 μg)<br>* iloprost inhalation solution (Ventavis) (5 μg)<br>Drug: Sildenafil<br>* oral sildenafil (dosage between 60 and 300 mg/day)<br>Drug: Bosentan<br>* oral bosentan (dosage between 62.5 and 125 mg BID)<br>|
| Experimental: DB inhaled iloprost 4x/day<br>Inhaled iloprost (5 μg) 4×/day plus inhaled placebo 2x/day plus sildenafil with or without bosentan during the double blind period | Drug: Inhaled Iloprost (5 μg)<br>* iloprost inhalation solution (Ventavis) (5 μg)<br>Drug: Inhaled Placebo<br>* inhaled placebo<br>Drug: Sildenafil<br>* oral sildenafil (dosage between 60 and 300 mg/day)<br>Drug: Bosentan<br>* oral bosentan (dosage between 62.5 and 125 mg BID)<br>|
| Placebo Comparator: DB inhaled placebo 6x/day<br>Inhaled placebo 6×/day plus sildenafil with or without bosentan during the double blind period | Drug: Inhaled Placebo<br>* inhaled placebo<br>Drug: Sildenafil<br>* oral sildenafil (dosage between 60 and 300 mg/day)<br>Drug: Bosentan<br>* oral bosentan (dosage between 62.5 and 125 mg BID)<br>|
| Experimental: OL inhaled iloprost 6x/day<br>Inhaled iloprost (5 μg) 6 times per day (6×/day) plus sildenafil with or without bosentan during the Open-Label treatment period | Drug: Inhaled Iloprost (5 μg)<br>* iloprost inhalation solution (Ventavis) (5 μg)<br>|
| Experimental: OL inhaled iloprost 4x/day<br>Inhaled iloprost (5 μg) 4 times per day (4×/day) plus sildenafil with or without bosentan during the Open-Label treatment period | Drug: Inhaled Iloprost (5 μg)<br>* iloprost inhalation solution (Ventavis) (5 μg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline to Week 16 in 6-Minute Walk Distance (6MWD) During the Double-blind Treatment Period | The 6MWD test is a non-encouraged test, performed in a 30-meter long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones during 6 minutes. They can slow down, rest, or stop if needed. This test is used to assess exercise capacity. The test was performed about 30 minutes after study drug administration. Any increase in the walk distance was considered improvement from baseline. | Day 1 and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With WHO Functional Class (WHO FC) Improvement at Week 16 | This test is used to assess disease severity. Four fucntional classes (FC) are defined from FC I (no limitation of physical activity) to FC IV (inability to carry out any physical activity without symptoms). Improvement is considered when a participant changes from a higher class to a lower class. | Day 1 and Week 16 | 
| Time to Clinical Worsening | Clinical worsening is defined as one of the following: death due to worsening PAH, receipt of lung or heart-lung transplantation, or atrial septostomy, hospitalization for worsening PAH, any early discontinuation from study during the blinded or open-label phase due to worsening PAH, initiation of additional PAH-specific treatment. Due to insufficient data, time could not be assessed accurately and only number of patients with clinical worsening could be reported. | Week 16 and Week 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PAH, Pulmonary Arterial Hypertension