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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VentaProst | Experimental | VentaProst (epoprostenol solution for inhalation via custom drug delivery system) In Part 1, subjects were treated with a commercial aerosolized epoprostenol and then removed from that treatment. VentaProst was started and titrated to a dose equivalence to maintain at least 90% of hemodynamic response seen with the commerical product. In Part 2, subjects were treated with VentaProst only. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VentaProst | Combination Product | epoprostenol for inhalation via custom drug delivery system |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
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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:
For patients in Part II:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles Hill, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Medical Center | Stanford | California | 94305 | United States | ||
| Rush University Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | VentaProst | VentaProst (epoprostenol solution for inhalation via custom drug delivery system) 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Epoprostenol Then VentaProst |
| |||||||||||||
| Part 2: VentaProst Dose Escalation |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Part 2: VentaProst Dose Escalation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per protocol population (Part I) | Posted | Number | ng/kg/min | 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) |
|
Adverse events were collect from post-cardiac surgery (Day 1) through study completion (up to 30 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: Epoprostenol Then VentaProst | an equivalent dose of VentaProst compared to conventionally-administered aerosolized epoprostenol |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pulmonary hypertension | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| coagulopathy | Blood and lymphatic system disorders | MedDRA (20.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Durand, MD | Aerogen Pharma | 510-928-2111 | ddurand@aerogenpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 28, 2017 | Feb 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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| Chicago |
| Illinois |
| 60612 |
| United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
Dose titration to achieve a clinically significant hemodynamic response. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | Kg |
|
|
|
| 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. | Per protocol population (Part II) | Posted | Number | ng/kg/min | 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) |
|
|
|
| 0 |
| 7 |
| 1 |
| 7 |
| 2 |
| 7 |
| EG001 | Part 2: VentaProst Dose Escalation | Dose titration to achieve a clinically significant hemodynamic response. | 0 | 8 | 2 | 8 | 1 | 8 |
| arterial hemorrhage | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| adrenal insufficiency | Endocrine disorders | MedDRA (20.0) | Systematic Assessment |
|
| acute kidney injury | Renal and urinary disorders | MedDRA (20.0) | Systematic Assessment |
|
| acute lung injury | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| traumatic hemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| arterial hemorrhage | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
| hemorrhage | Vascular disorders | MedDRA (20.0) | Systematic Assessment |
|
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| D002318 |
| Cardiovascular Diseases |
|
| Optimal VP dose 3 |
|
|