Clinical trial NCT03122730: VentaProst Versus Conventionally-Administered Aerosolized Epoprostenol in Patients Undergoing 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Keywords: Cardiac surgery
Cardiopulmonary bypass
Epoprostenol
Lead sponsor: Aerogen Pharma Limited
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determination of the equivalent dose of VentaProst necessary to achieve a pharmacodynamic response that is comparable to Standard of Care
timeFrame: 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 outcomes:
measure: Treatment-Emergent Adverse Events (TEAEs)
timeFrame: The incidence of TEAEs will be monitored from post cardiac surgery (Day 1) through study completion (up to 30 days)
measure: Effects on pulmonary vascular resistance
timeFrame: 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)
measure: Effects on oxygenation status
timeFrame: 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)
measure: Effects on fraction of inspired oxygen (FiO2)
timeFrame: 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)
measure: Effects on cardiovascular medication usage
timeFrame: 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)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Stanford University
name: Charles Hill, MD
role: PRINCIPAL_INVESTIGATOR
References: