VentaProst Versus Conventionally-Administered Aerosolized Epoprostenol in Patients Undergoing Cardiac Surgery With CPB

Study Overview
=================
Brief Summary
-----------------
The purpose of the Phase 2a study is to: 1) demonstrate that the estimated VentaProst dose is safe and equivalent in effect to a dose administered via epoprostenol aerosolization by the current off-label-use practice; and 2) demonstrate that an optimum effect can be rapidly obtained with VentaProst titration.

Detailed Description
-----------------
Part I: This part of the study is designed to demonstrate the dose equivalence between off-label aerosolized epoprostenol and VentaProst using a patient's hemodynamic parameters. Part II: This part of the study is designed to establish a dose response relationship of VentaProst to hemodynamic effect by dose escalation in patients who have had cardiac surgery with CPB.

Official Title
-----------------
A Two-Part Pharmacodynamic Study to Compare VentaProst (Epoprostenol Solution for Inhalation Via Custom Drug Delivery System) Dosing to Conventionally Administered Aerosolized Epoprostenol Dosing in Cardiac Surgery Patients

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

Intervention / Treatment
-----------------
* Combination Product: VentaProst


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women and Men 18 to 75 years of age Provide written informed consent Willing and able to comply with all aspects of the protocol For patients in Part I: Undergo cardiac surgery on CPB Clinically require treatment with and receive aerosolized epoprostenol Demonstrate a clinically meaningful hemodynamic response to aerosolized epoprostenol For patients in Part II: Undergo cardiac surgery with CPB Have perioperative pulmonary hypertension Clinically require treatment with inhaled epoprostenol Exclusion Criteria: Current smoker (i.e., within the last 30 days) Emergency operative status Upper and/or lower respiratory tract infection within four weeks of screening Contraindication to transesophageal echocardiogram (TEE) including esophageal disease or unstable cervical spine Renal or severe hepatic impairment Thromboembolic disease treated with anticoagulant therapy Bleeding disorders Significant restrictive or obstructive lung disease History of concurrent malignancy or recurrence of malignancy within two years prior to Screening History of a diagnosis of drug or alcohol dependency or abuse within approximately the last three years Recent history of stroke or transient ischemic attack Significantly abnormal laboratory tests at Screening Pregnant or breastfeeding Treatment with an investigational drug, biologic, or device within 30 days Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the patient inappropriate for entry into this trial Any condition where aerosolized epoprostenol is contraindicated Known allergy or sensitivity to epoprostenol, any of its ingredients, or the diluent

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VentaProst<br>VentaProst (epoprostenol solution for inhalation via custom drug delivery system) | Combination Product: VentaProst<br>* Part I - an equivalent dose of VentaProst compared to conventionally-administered aerosolized epoprostenol with subsequent dose titration to achieve a clinically significant hemodynamic response Part II - Dose titration to achieve a clinically significant hemodynamic response.<br>* Other names: epoprostenol for inhalation via custom drug delivery system;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the equivalent dose of VentaProst necessary to achieve a pharmacodynamic response that is comparable to Standard of Care | Improvement in pharmacodynamic parameters (based on changes in hemodynamic parameters, indices of oxygenation, and ventilator support) | Pharmacodynamic changes will be measured during surgery (Day 1), post-surgery (Day 1), and from start of study treatment (Day 1) through study completion (up to 30 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-Emergent Adverse Events (TEAEs) | Monitoring of adverse events, complications, surgeries, transfusions, physical exams, clinical laboratory tests, and ECGs | The incidence of TEAEs will be monitored from post cardiac surgery (Day 1) through study completion (up to 30 days) | 
| Effects on pulmonary vascular resistance | Changes in pulmonary vascular resistance | Changes in pulmonary vascular resistance will be measured prior to surgery (Day 1), during surgery (Day 1), post-surgery (Day 1), and from start of study treatment (Day 1) through study completion (up to 30 days) | 
| Effects on oxygenation status | Changes in arterial oxygen saturation | Changes in arterial oxygen saturation will be measured prior to surgery (Day 1), during surgery (Day 1), post-surgery (Day 1), and from start of study treatment (Day 1) through study completion (up to 30 days) | 
| Effects on fraction of inspired oxygen (FiO2) | Changes in fraction of inspired oxygen (FiO2) | Changes in FiO2 will be measured prior to surgery (Day 1), during surgery (Day 1), post-surgery (Day 1), and from start of study treatment (Day 1) through study completion (up to 30 days) | 
| Effects on cardiovascular medication usage | Changes in the number and type of cardiovascular medications | Changes in cardiovascular medication usage will be measured prior to surgery (Day 1), during surgery (Day 1), post-surgery (Day 1), and from start of treatment (Day 1) through study completion (up to 30 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiac surgery, Cardiopulmonary bypass, Epoprostenol