Clinical trial NCT00903604: Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery
Official title: Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Surgery
Coronary Artery Bypass Grafting
Valve Surgery
Aortic Root or Ascending Aortic Aneurysm Repair Surgery
Keywords: Cardiac surgery
coronary artery bypass grafting
valve surgery
aortic root or ascending aortic aneurysm repair surgery
Acute kidney injury
Lead sponsor: Action Pharma A/S
Sponsor class: INDUSTRY
First posted: 2009-05-18
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Has signed the trial-specific informed consent form.
2. Patients ≥ 18 years old, male or female, not of childbearing potential (postmenopausal or permanently sterilized, e.g. tubal ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
3. Patients undergoing CABG, valve(s), CABG/valve(s) and/or aortic root or ascending aortic aneurysm repair surgery.
4. Cleveland Clinic Renal Score ≥ 2 (higher than average risk for AKI).
5. EF ≥ 30%, evaluated within 2 months prior to screening visit.

Exclusion Criteria:

1. Cardiac surgery to be performed "off pump" without cardiopulmonary bypass.
2. Circulatory arrest in connection with aortic root or ascending aortic aneurysm repair surgery.
3. Confirmed or suspected endocarditis.
4. Requiring a reoperation on one of the valves within 3 months following the original valve surgical procedure.
5. Receiving Aprotinin during the trial, from Screening to Day 90.
6. Having undergone cardiovascular catheterization ≤ 48 hours prior to scheduled surgery.
7. Active peptic ulcer disease and gastritis.
8. Hemoccult positive stools, hematological, bleeding, and coagulation disorders.
9. Receiving dopamine at renal doses (2-4 mcg/kg/min), from Screening to Day of surgery.
10. S-Creatinine greater than 2.1 mg/dl.
11. Known or suspected hypersensitivity to the investigational medicinal product.
12. Known or suspected hypersensitivity to Ondansetron or other selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
13. Current participation in any other interventional clinical trial.
14. Previously dosed with AP214.
15. Use of investigational medicinal products within the previous 6 months.
16. Body weight above 140 kg.
17. History of any organ transplant.
18. Women who are of childbearing potential, pregnant, or breast-feeding.
19. Current abuse of alcohol or substance, according to the investigator's medical judgment.
20. Has a mental incapacity or language barriers precluding adequate understanding of trial procedures.
21. Is considered by the Investigator unsuitable to participate in the trial for any other reason, for instance due to a significant serious underlying condition.

Primary outcomes:
measure: To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery.
timeFrame: Day 0 to Day 1
measure: 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)
timeFrame: Day 0-90
Secondary outcomes:
measure: 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
timeFrame: 0-24 hours
measure: 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.
timeFrame: Day 0 - Day 30
measure: To assess the safety and tolerability of AP214 on standard safety laboratory data
timeFrame: Day 0-14
measure: To assess the safety and tolerability of AP214 on vital signs
timeFrame: Day 0-90
measure: To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality
timeFrame: Day 0-90
measure: To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically.
timeFrame: Day 0-90
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery
Study officials:
affiliation: Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet
name: Daniel Steinbrüchel, Professor
role: PRINCIPAL_INVESTIGATOR
References: