CTI-01 (Ethyl Pyruvate) Safety and Complication Prevention in Cardiac Surgery Patients on Cardiopulmonary Bypass (CPB)

Coronary Disease Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Proof of Concept Clinical Study of CTI-01 in Patients Undergoing Major Cardiac Surgery With Cardiopulmonary Bypass

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00107666
• Other study ID #: CTI-01-C04-201
• Status: Terminated
• Phase: Phase 2
• First received: April 6, 2005
• Last updated: March 15, 2006
• Start date: April 2005
• Est. completion date: April 2006

Study information

• Verified date: March 2006
• Source: Critical Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Over 500,000 patients undergo cardiac surgery with CPB in the United States annually. Although mortality rates have decreased with advances in perioperative care, many patients are affected by postoperative organ dysfunction. The incidence of complications may exceed 30%. It has been speculated that an exaggerated inflammatory response to surgical trauma and the CPB machine are likely causes for this morbidity. Factors predisposing organ dysfunction include tissue injury, endotoxemia, and oxidative stress. High risk patients can be identified preoperatively through the validated Parsonnet Additive Risk Score. CTI-01 has demonstrated potent anti-inflammatory and tissue protection activity in multiple animal models of disease including pancreatitis, ischemia-reperfusion injury, sepsis, renal injury, and endotoxemia. These findings support its clinical use in critical care medicine including cardiac surgery. Patients will receive a total of six doses, administered intravenously just prior to and after surgery.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 150
• Est. completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Parsonnet additive risk score greater than or equal to 15

• Scheduled CABG (coronary artery bypass grafting) and/or cardiac valve repair or replacement surgery using cardiopulmonary bypass

Exclusion Criteria:

• Emergency cardiac surgery

• Significant concomitant surgery

• Minimally invasive or thoracic surgical approach

• Preoperative mechanical assist device

• Body weight <50 kg or >140 kg

• Active systemic infection

• Creatinine >3.0 mg/dL

• History of hematologic or coagulation disorders

• History of malignancy (past year)or organ transplantation

• Use of immunosuppressive drugs or current immunosuppressed condition

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Valve Diseases

Intervention

Drug:
• CTI-01 (ethyl pyruvate)

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	East Carolina University - Brody School of Medicine	Greenville	North Carolina
United States	St. Luke's Episcopal Hospital/Texas Heart Institute	Houston	Texas
United States	Saddleback Memorial Medical Center	Laguna Hills	California
United States	University of Southern California	Los Angeles	California
United States	Medical College of Wisconsin - VA Medical Center	Milwaukee	Wisconsin
United States	NYU Medical Center	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Kaiser Permanente	San Francisco	California
United States	Baystate Medical Center	Springfield	Massachusetts
United States	MultiCare Health System	Tacoma	Washington
United States	Washington Hospital Center	Washington	District of Columbia
United States	Chester County Hospital - The Cardiovasular Center	West Chester	Pennsylvania
United States	Research Support Personnel	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Critical Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (5)

Bennett-Guerrero E, Ayuso L, Hamilton-Davies C, White WD, Barclay GR, Smith PK, King SA, Muhlbaier LH, Newman MF, Mythen MG. Relationship of preoperative antiendotoxin core antibodies and adverse outcomes following cardiac surgery. JAMA. 1997 Feb 26;277(8):646-50. — View Citation

Fink MP. Ethyl pyruvate: a novel anti-inflammatory agent. Crit Care Med. 2003 Jan;31(1 Suppl):S51-6. Review. — View Citation

Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation. 1989 Jun;79(6 Pt 2):I3-12. Erratum in: Circulation 1990 Sep;82(3):1078. — View Citation

Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R, Czura CJ, Fink MP, Tracey KJ. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12351-6. Epub 2002 Sep 3. — View Citation

Woo YJ, Taylor MD, Cohen JE, Jayasankar V, Bish LT, Burdick J, Pirolli TJ, Berry MF, Hsu V, Grand T. Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia. J Thorac Cardiovasc Surg. 2004 May;127(5):1262-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death
Primary	Composite morbidity endpoint
Secondary	Respiratory dysfunction
Secondary	Cardiac dysfunction
Secondary	Renal dysfunction
Secondary	Gastrointestinal dysfunction
Secondary	Mental status
Secondary	Length of ICU (Intensive Care Unit)/hospital stay