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The purpose of the present research study is to investigate the pharmacokinetics, as well as safety, tolerability and pharmacodynamics of different ascending dosing regimens of AP214 in patients undergoing cardiac surgery. AP214, the investigational drug, is being developed to potentially prevent post-surgical kidney injury after thoracic aortic aneurysm repair.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AP214 | Experimental | Infusions of sequential ascending dosages of AP214 |
|
| Placebo | Placebo Comparator | Infusions of saline solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AP214 | Drug | Three 10-minutes infusions of sequential ascending dosages of AP214 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery. | Day 0 to Day 1 | |
| To assess the safety and tolerability of AP214, defined as a descriptive analysis of AEs and SAEs (including analysis of severity and relationship to trial drug) | Day 0-90 |
| Measure | Description | Time Frame |
|---|---|---|
| To assess effect of AP214 on cardiac surgery induced systemic inflammation o determined by the post-operative peak plasma concentrations of TNF-α, IL-6, IL-8, and IL-10, and area under the curve (AUC) for TNF-α, IL-6, IL-8, and IL-10 | 0-24 hours | |
| To assess effect of AP214 on development of post-surgical acute kidney injury (AKI), where AKI is evaluated by evaluation of serum creatinine values, urine output and renal replacement therapy free days. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Steinbrüchel, Professor | Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet | Copenhagen | 2100 | Denmark | |||
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| Placebo |
| Drug |
Three 10-minutes infusions of isotonic saline solution |
|
| Day 0 - Day 30 |
| To assess the safety and tolerability of AP214 on standard safety laboratory data | Day 0-14 |
| To assess the safety and tolerability of AP214 on vital signs | Day 0-90 |
| To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality | Day 0-90 |
| To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically. | Day 0-90 |
| Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery |
| Odense |
| 5000 |
| Denmark |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |