Effects of Ventavis in Patients With Pulmonary Hypertension (PH) Secondary to Chronic Obstructive Pulmonary Disease (COPD)

A Phase 2, Multi-center, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of Inhaled Iloprost on Endurance Time During Cardiopulmonary Exercise Testing in Patients With Pulmonary Hypertension Secondary to Chronic Obstructive Pulmonary Disease

This is a phase 2, Multi-center, double-blind, randomized, placebo-controlled study to evaluate the effects of inhaled Iloprost in patients with pulmonary hypertension secondary to COPD. The main objective is to investigate the effect of iloprost on exercise endurance time during constant work rate cardiopulmonary exercise testing. Other efficacy and safety endpoints will additionally be analyzed.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Iloprost

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Vandoeuvre-lès-Nancy, France, 54500
    • Hopital d'adultes de Brabois
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
• United States
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study mandated procedure
2. Male or female ≥ 40 and ≤ 75 years of age
3. Women of childbearing potential1 must use a reliable method of contraception
4. Clinical diagnosis of moderate to severe COPD, with an obstructive pattern on pulmonary function tests
5. Current or past smokers of ≥ 10 pack years
6. Ability to perform exercise testing without supplemental oxygen (in the best opinion of the investigator)
7. Confirmed pulmonary hypertension by right heart catheterization (RHC)

Exclusion Criteria:

1. Other causes of pulmonary hypertension than COPD
2. BMI > 35 kg/m2
3. Conditions considered as contraindications for cardiopulmonary exercise testing (CPET) and/or inability to pedal on a cycle ergometer
4. Pregnant or nursing
5. Currently (within 30 days prior to RHC) taking specific pulmonary arterial hypertension (PAH) therapy (e.g., bosentan, ambrisentan, tadalafil, sildenafil, epoprostenol, treprostinil, iloprost, beraprost)
6. Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to RHC visit
7. Known concomitant life-threatening disease with a life expectancy < 12 months
8. Known hypersensitivity to iloprost or any of the excipients of the drug formulations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: iloprost; single dose inhalation using the power disc-6 with I-neb Adaptive Aerosol Delivery (AAD) system	Drug: Iloprost; 5ug dose of inhaled iloprost (20ug/mL solution) administered 6 to 9 times per day for 4 weeks; Other Names: Ventavis
PLACEBO_COMPARATOR: placebo; matching placebo using the power disc-6 with I-neb AAD system	Drug: Placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endurance Time	Change from baseline to week 4 in endurance time during constant work rate exercise testing	Baseline to week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Treatment-emergent Adverse Events	Treatment-emergent adverse events up to 24 hours post-end of treatment (EOT), approximately 4 weeks	Baseline up to 24 hours post-EOT, approximately 4 weeks
Change in Systolic Pulmonary Arterial Pressure	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Diastolic Pulmonary Arterial Pressure	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Mean Pulmonary Arterial Pressure	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Mean Right Atrial Pressure	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Cardiac Output	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Right Ventricular Pressure	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in Pulmonary Vascular Resistance	On Day 1 patients underwent acute hemodynamic testing prior to and immediately after (no more than 15 minutes) the first dose of inhaled iloprost or placebo. All hemodynamic variables were measured using a Swan-Ganz catheter.	15 minutes
Change in End Tidal Partial Pressure of Carbon Dioxide	Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in End Tidal Partial Pressure of Oxygen	Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Oxygen Uptake	Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Carbon Dioxide Output	Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Oxygen Uptake Per Heartbeat	Change from baseline to week 4. Pulmonary gas exchange was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Heart Rate	Change from baseline to week 4. Heart rate was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Arterial Oxygen Saturation as Indicated by Pulse Oximetry	Change from baseline to week 4. Arterial oxygen was determined by pulse oximetry during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Tidal Volume	Change from baseline to week 4. Tidal volume was measured during incremental and constant work rate exercise testing.	Baseline to week 4
Change in Minute Ventilation	Change from baseline to week 4. Minute ventilation was measured during incremental and constant work rate exercise testing.	Baseline to week 4

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Frederic Bodin, MD, Actelion

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 20, 2011
• First Posted (ESTIMATE): September 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 20, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: COPD; PH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: AC-063B201