Safety, Tolerability and Pharmacodynamics of AP214 Acetate in Patients Undergoing Cardiac Surgery - Full Text View

Sponsored by:	Action Pharma A/S
Information provided by:	Action Pharma A/S
ClinicalTrials.gov Identifier:	NCT00628264

Purpose

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.

Condition	Intervention	Phase
Cardiac Surgery Coronary Artery Bypass Grafting Valve Surgery Kidney Injury	Drug: AP214 Drug: Placebo	Phase II

MedlinePlus related topics: Coronary Artery Bypass Surgery Heart Surgery

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Safety, Tolerability and Pharmacodynamics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Further study details as provided by Action Pharma A/S:

Primary Outcome Measures:

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). [ Time Frame: From day 0-14 ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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) [ Time Frame: Day 0-90 ] [ Designated as safety issue: No ]
To assess the impact of AP214 on cardiac surgery induced systemic inflammatory response syndrome (post-operative peak plasma concentrations of TNF-α and IL-8 and AUC for TNF-α, IL-6, IL-8 and IL-10). [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
To assess the impact of AP214 for renal protection as measured by the development of post-surgical acute kidney injury (AKIN score) [ Time Frame: Day 0-14 ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	75
Study Start Date:	March 2008
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Has signed the trial specific informed consent form.
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.
Patients undergoing CABG, valve(s), CABG/valve and/or aortic root or ascending aortic aneurysm repair surgery.
Cleveland Clinic Renal Score ≥ 2 (higher than average risk for AKI).
EF ≥ 30%, evaluated within 2 months prior to screening visit.

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628264

Contacts

Contact: Thomas M Beaver, MD, MPH	(352) 273-5503 ext -	beavetm@surgery.ufl.edu
Contact: Jennifer West, Nurse	(352)273-5493	jennifer.west@surgery.ufl.edu

Locations

United States, Florida
Shands Hospital at University of Florida	Recruiting
Gainesville, Florida, United States, 32610
Shands Hospital at Alachua General Hospital	Recruiting
Gainesville, Florida, United States, 32601

Sponsors and Collaborators

Action Pharma A/S

Investigators

Principal Investigator:

Thomas M Beaver, MD, MPH

Division of Thoracic and Cardiovascular Surgery , University of Florida College of Medicine

More Information

Responsible Party:	Action Pharma A/S ( Action Pharma A/S )
Study ID Numbers:	AP214-CS004
Study First Received:	February 25, 2008
Last Updated:	November 25, 2008
ClinicalTrials.gov Identifier:	NCT00628264
Health Authority:	United States: Food and Drug Administration

Keywords provided by Action Pharma A/S:

cardiac surgery
coronary artery bypass grafting
valve surgery
acute kidney injury

ClinicalTrials.gov processed this record on January 16, 2009