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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Combination product: VentaProst

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Women and Men 18 to 75 years of age
2. Provide written informed consent
3. Willing and able to comply with all aspects of the protocol

4. For patients in Part I:

   1. Undergo cardiac surgery on CPB
   2. Clinically require treatment with and receive aerosolized epoprostenol
   3. Demonstrate a clinically meaningful hemodynamic response to aerosolized epoprostenol

5. For patients in Part II:

   1. Undergo cardiac surgery with CPB
   2. Have perioperative pulmonary hypertension
   3. Clinically require treatment with inhaled epoprostenol

Exclusion Criteria:

1. Current smoker (i.e., within the last 30 days)
2. Emergency operative status
3. Upper and/or lower respiratory tract infection within four weeks of screening
4. Contraindication to transesophageal echocardiogram (TEE) including esophageal disease or unstable cervical spine
5. Renal or severe hepatic impairment
6. Thromboembolic disease treated with anticoagulant therapy
7. Bleeding disorders
8. Significant restrictive or obstructive lung disease
9. History of concurrent malignancy or recurrence of malignancy within two years prior to Screening
10. History of a diagnosis of drug or alcohol dependency or abuse within approximately the last three years
11. Recent history of stroke or transient ischemic attack
12. Significantly abnormal laboratory tests at Screening
13. Pregnant or breastfeeding
14. Treatment with an investigational drug, biologic, or device within 30 days
15. 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
16. Any condition where aerosolized epoprostenol is contraindicated
17. Known allergy or sensitivity to epoprostenol, any of its ingredients, or the diluent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VentaProst; VentaProst (epoprostenol solution for inhalation via custom drug delivery system)	Combination product: VentaProst; 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.; 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)

Collaborators and Investigators

• Sponsor: Aerogen Pharma Limited
• Investigators: Principal Investigator: Charles Hill, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2017
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): May 30, 2019

Study Registration Dates

• First Submitted: April 11, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): May 31, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Cardiac surgery; Cardiopulmonary bypass; Epoprostenol
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Platelet Aggregation Inhibitors; Epoprostenol
• Other Study ID Numbers: APC-VP-CLN-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No