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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Chronic Obstructive Pulmonary Disease, Pulmonary Hypertension

Intervention / Treatment
-----------------
* Drug: Iloprost
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent prior to initiation of any study mandated procedure Male or female ≥ 40 and ≤ 75 years of age Women of childbearing potential1 must use a reliable method of contraception Clinical diagnosis of moderate to severe COPD, with an obstructive pattern on pulmonary function tests Current or past smokers of ≥ 10 pack years Ability to perform exercise testing without supplemental oxygen (in the best opinion of the investigator) Confirmed pulmonary hypertension by right heart catheterization (RHC) Exclusion Criteria: Other causes of pulmonary hypertension than COPD BMI > 35 kg/m2 Conditions considered as contraindications for cardiopulmonary exercise testing (CPET) and/or inability to pedal on a cycle ergometer Pregnant or nursing Currently (within 30 days prior to RHC) taking specific pulmonary arterial hypertension (PAH) therapy (e.g., bosentan, ambrisentan, tadalafil, sildenafil, epoprostenol, treprostinil, iloprost, beraprost) Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to RHC visit Known concomitant life-threatening disease with a life expectancy < 12 months Known hypersensitivity to iloprost or any of the excipients of the drug formulations

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Triple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PH, COPD