Safety, Tolerability and Pharmacodynamics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Action Pharma

Status and phase: Terminated; Phase 2

Conditions: Cardiac Surgery; Kidney Injury; Valve Surgery; Coronary Artery Bypass Grafting

Treatments: Drug: Placebo; Drug: AP214

Study type: Interventional

Funder types: Industry

Identifiers

NCT00628264

AP214-CS004

Details and patient eligibility

About

The purpose of the present research study is to investigate for the first time, the safety and tolerability of infusion doses of AP214 in subjects having heart surgery such as coronary bypass graft and/or valve repair or replacement surgery. AP214, the investigational drug, is being developed to potentially prevent post-surgical kidney injury after thoracic aortic aneurysm repair.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 occlusion, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
3. Patients undergoing CABG, valve(s), CABG/valve 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 90.
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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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75 participants in 2 patient groups, including a placebo group

AP214

Experimental group

Treatment:

Drug: AP214

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo