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Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Primary Purpose

Cardiac Surgery, Coronary Artery Bypass Grafting, Valve Surgery

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

AP214

Placebo

About this trial

This is an interventional prevention trial for Cardiac Surgery focused on measuring Cardiac surgery, coronary artery bypass grafting, valve surgery, aortic root or ascending aortic aneurysm repair surgery, Acute kidney injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity.
Patients undergoing CABG, valve(s), CABG/valve(s) 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 of surgery.
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.

Sites / Locations

Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet
Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AP214

Placebo

Arm Description

Infusions of sequential ascending dosages of AP214

Infusions of saline solution

Outcomes

Primary Outcome Measures

To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery.

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)

Secondary Outcome Measures

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

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.

To assess the safety and tolerability of AP214 on standard safety laboratory data

To assess the safety and tolerability of AP214 on vital signs

To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality

To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically.

Full Information

NCT ID

NCT00903604

First Posted

May 15, 2009

Last Updated

May 16, 2011

Sponsor

Action Pharma A/S

1. Study Identification

Unique Protocol Identification Number

NCT00903604

Brief Title

Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Official Title

Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

May 2011

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Action Pharma A/S

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AP214

Arm Type

Experimental

Arm Description

Infusions of sequential ascending dosages of AP214

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Infusions of saline solution

Intervention Type

Drug

Intervention Name(s)

AP214

Intervention Description

Three 10-minutes infusions of sequential ascending dosages of AP214

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Three 10-minutes infusions of isotonic saline solution

Primary Outcome Measure Information:

Title

To assess in patients the pharmacokinetics of AP214 administered as three 10-minute infusions in patients undergoing cardiac surgery.

Time Frame

Day 0 to Day 1

Title

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)

Time Frame

Day 0-90

Secondary Outcome Measure Information:

Title

Time Frame

0-24 hours

Title

Time Frame

Day 0 - Day 30

Title

To assess the safety and tolerability of AP214 on standard safety laboratory data

Time Frame

Day 0-14

Title

To assess the safety and tolerability of AP214 on vital signs

Time Frame

Day 0-90

Title

To assess safety and tolerability of AP214 in terms of mortality by evaluation of overall mortality

Time Frame

Day 0-90

Title

To assess the effect of AP214 at an organ level (CNS, heart, lung, and wound healing)as well as systemically.

Time Frame

Day 0-90

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 ligation, hysterectomy, bilateral salpingectomy), regardless of ethnicity. Patients undergoing CABG, valve(s), CABG/valve(s) 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 of surgery. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel Steinbrüchel, Professor

Organizational Affiliation

Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Cardiac and Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Odense University Hospital, Department of Cardiac, Thoracic and Vascular Surgery

City

Odense

ZIP/Postal Code

5000

Country

Denmark

12. IPD Sharing Statement

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Pharmacokinetics of AP214 Acetate in Patients Undergoing Cardiac Surgery

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