Pulmonary Hypertension
Conditions
Keywords
Cardiac surgery, Cardiopulmonary bypass, Epoprostenol
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.
Interventions
COMBINATION_PRODUCTVentaProst
epoprostenol for inhalation via custom drug delivery system
Sponsors
Aerogen Pharma Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identify Equivalent Dose of VentaProst Necessary to Achieve a PD Response Comparable to Standard of Care Treatment (Part I) | 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) | The primary goal was to establish the dose of VentaProst necessary to achieve a PD response comparable to the standard of care. The first dose of VentaProst tested, 17 ng/kg/min, achieved the dose equivalency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Optimal Dose Determination With VP Dose Escalation (Part II) | 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) | Calculate vascular resistance indicators for CI and CO, and PAPi at each dose level. Identify the VP dose where mPAP, VR(CO), VR(CI), CVP are lowest, and CI/CO are highest. Compare in a narrative to the selected VP optimal dose by the Investigator by individual patient. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Epoprostenol Then VentaProst an equivalent dose of VentaProst compared to conventionally-administered aerosolized epoprostenol with subsequent dose titration to achieve a clinically significant hemodynamic response | 7 |
| Part 2: VentaProst Dose Escalation Dose titration to achieve a clinically significant hemodynamic response. | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Part 1: Epoprostenol Then VentaProst | Total | Part 2: VentaProst Dose Escalation |
|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 11.47 | 65.8 years STANDARD_DEVIATION 9.41 | 65.6 years STANDARD_DEVIATION 8.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
| Weight | 85.6 Kg STANDARD_DEVIATION 21.11 | 84.5 Kg STANDARD_DEVIATION 18.61 | 83.6 Kg STANDARD_DEVIATION 17.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 2 / 7 | 1 / 8 |
| serious Total, serious adverse events | 1 / 7 | 2 / 8 |
Outcome results
Primary
Identify Equivalent Dose of VentaProst Necessary to Achieve a PD Response Comparable to Standard of Care Treatment (Part I)
The primary goal was to establish the dose of VentaProst necessary to achieve a PD response comparable to the standard of care. The first dose of VentaProst tested, 17 ng/kg/min, achieved the dose equivalency.
Time frame: 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)
Population: Per protocol population (Part I)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VentaProst | Identify Equivalent Dose of VentaProst Necessary to Achieve a PD Response Comparable to Standard of Care Treatment (Part I) | 17 ng/kg/min |
Secondary
Optimal Dose Determination With VP Dose Escalation (Part II)
Calculate vascular resistance indicators for CI and CO, and PAPi at each dose level. Identify the VP dose where mPAP, VR(CO), VR(CI), CVP are lowest, and CI/CO are highest. Compare in a narrative to the selected VP optimal dose by the Investigator by individual patient.
Time frame: 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)
Population: Per protocol population (Part II)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VentaProst | Optimal Dose Determination With VP Dose Escalation (Part II) | Optimal VP dose 1 | 6.8 ng/kg/min |
| VentaProst | Optimal Dose Determination With VP Dose Escalation (Part II) | Optimal VP dose 2 | 10.2 ng/kg/min |
| VentaProst | Optimal Dose Determination With VP Dose Escalation (Part II) | Optimal VP dose 3 | 13.6 ng/kg/min |