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

Cardiac Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00628264
• Other study ID #: AP214-CS004
• Status: Terminated
• Phase: Phase 2
• First received: February 25, 2008
• Last updated: May 29, 2009
• Start date: March 2008
• Est. completion date: June 2009

Study information

• Verified date: May 2009
• Source: Action Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 75
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiac Surgery
• Coronary Artery Bypass Grafting
• Kidney Injury
• Valve Surgery

Intervention

Drug:
• AP214
Three AP214 bolus infusions administered over 10 minutes (prior to skin incision, at time of clamp-release and 6 hours after clamp-release).
• Placebo
Three placebo bolus infusions administered over 10 minutes (prior to skin incision, at time of clamp-release and 6 hours after clamp-release).

Locations

Country	Name	City	State
United States	Shands Hopsital at University of Florida	Gainesville	Florida
United States	Shands Hospital at Alachua General Hospital	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Action Pharma A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the safety and tolerability of AP214 administered as three 10-minute bolus infusions, in patients undergoing cardiac surgery that are at increased risk of AKI (descriptive analysis of AEs and SAEs from Day 0-14).		From day 0-14	No
Primary	To assess the impact of AP214 on cardiac surgery induced systemic inflammatory response syndrome determined by the post-operative peak plasma concentrations of IL-6 and IL-10 from 0-24 hours		0-24 hours	No
Secondary	To assess the safety and tolerability of AP214 at an organ level as well as in terms of the overall mortality (heart, CNS, lung, wound, mortality)		Day 0-90	No
Secondary	To assess the impact of AP214 on cardiac surgery induced systemic inflammatory response syndrome (post-operative peak plasma concentrations of TNF-a and IL-8 and AUC for TNF-a, IL-6, IL-8 and IL-10).		0-24 hours	No
Secondary	To assess the impact of AP214 for renal protection as measured by the development of post-surgical acute kidney injury (AKIN score)		Day 0-14	No
Secondary	To assess the impact of AP214 on the development of post-surgical left ventricular dysfunction (determined by changes in left ventricular function from pre to post coronary bypass by transesophageal echocardiography		0-24 hours	No