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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Inhaled Iloprost (5 μg); Drug: Sildenafil; Drug: Bosentan; Drug: Inhaled Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego Medical Center
    • Los Angeles, California, United States, 90073
      • GLVA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Medical Offices
    • Sacramento, California, United States, 95817
      • University of California Davis School of Medicine
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
    • Stanford, California, United States, 94305-5351
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Services
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1321
      • University of Connecticut Health Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Lombard, Illinois, United States, 60148
      • Midwest Heart Foundation
    • Lombard, Illinois, United States, 60148
      • Midwest Heart Specialists, Edwards Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University Of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts New England Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49506
      • Spectrum Blodgett Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Alleghany General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of SC School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Diagnostic Research Group
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Heart Care Associates, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 85 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DB inhaled iloprost 6x/day; 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); iloprost inhalation solution (Ventavis) (5 μg); Drug: Sildenafil; oral sildenafil (dosage between 60 and 300 mg/day); Drug: Bosentan; oral bosentan (dosage between 62.5 and 125 mg BID)
EXPERIMENTAL: DB inhaled iloprost 4x/day; 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); iloprost inhalation solution (Ventavis) (5 μg); Drug: Sildenafil; oral sildenafil (dosage between 60 and 300 mg/day); Drug: Bosentan; oral bosentan (dosage between 62.5 and 125 mg BID); Drug: Inhaled Placebo; inhaled placebo
PLACEBO_COMPARATOR: DB inhaled placebo 6x/day; Inhaled placebo 6×/day plus sildenafil with or without bosentan during the double blind period	Drug: Sildenafil; oral sildenafil (dosage between 60 and 300 mg/day); Drug: Bosentan; oral bosentan (dosage between 62.5 and 125 mg BID); Drug: Inhaled Placebo; inhaled placebo
EXPERIMENTAL: OL inhaled iloprost 6x/day; 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); iloprost inhalation solution (Ventavis) (5 μg)
EXPERIMENTAL: OL inhaled iloprost 4x/day; 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); iloprost inhalation solution (Ventavis) (5 μg)

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Events	This is the overall number of participants in each group who reported at least one adverse event (i.e., any untoward medical occurrence or unfavorable and unintended sign whether or not considered related to the study drug) with an onset from the first administration of study drug up to the last study visit.	From Day 1 to Week 16 and Week 48

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Principal Investigator: Nazzareno Galie, MD, Istituto Malattie Apparato Cardio Univ di Bologna

Publications and helpful links

Helpful Links

• CoTherix Clinical Development

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2006
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: March 10, 2006
• First Submitted That Met QC Criteria: March 10, 2006
• First Posted (ESTIMATE): March 14, 2006

Study Record Updates

• Last Update Posted (ACTUAL): April 16, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; PAH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Endothelin Receptor Antagonists; Iloprost; Sildenafil Citrate; Bosentan
• Other Study ID Numbers: C200-006