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

• Sponsor: Critical Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00107666
• Collaborator: (none)
• Enrollment: 150
• Locations: 17
• Duration (Months): 12
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Disease; Heart Valve Diseases	Drug: CTI-01 (ethyl pyruvate)	Phase 2

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Prevention
• 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
• Study Start Date: Apr 1, 2005
• Study Completion Date: Apr 1, 2006

Outcome Measures

Primary Outcome Measures

1. Death []

2. Composite morbidity endpoint []

Secondary Outcome Measures

1. Respiratory dysfunction []

2. Cardiac dysfunction []

3. Renal dysfunction []

4. Gastrointestinal dysfunction []

5. Mental status []

6. Length of ICU (Intensive Care Unit)/hospital stay []

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saddleback Memorial Medical Center	Laguna Hills	California	United States	92653
2	University of Southern California	Los Angeles	California	United States	90033
3	Kaiser Permanente	San Francisco	California	United States	94115
4	Washington Hospital Center	Washington	District of Columbia	United States	20010
5	University of Florida	Gainesville	Florida	United States	32610
6	Research Support Personnel	Wichita	Kansas	United States	67208
7	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
8	Baystate Medical Center	Springfield	Massachusetts	United States	01199
9	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
10	NYU Medical Center	New York	New York	United States	10016
11	Duke University Medical Center	Durham	North Carolina	United States	27710
12	East Carolina University - Brody School of Medicine	Greenville	North Carolina	United States	27834
13	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Chester County Hospital - The Cardiovasular Center	West Chester	Pennsylvania	United States	19380
15	St. Luke's Episcopal Hospital/Texas Heart Institute	Houston	Texas	United States	77030
16	MultiCare Health System	Tacoma	Washington	United States	98405
17	Medical College of Wisconsin - VA Medical Center	Milwaukee	Wisconsin	United States	53295

Sponsors and Collaborators

• Critical Therapeutics

Investigators

• Study Director: Walter Newman, Ph.D., Critical Therapeutics Incorporated

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• ClinicalTrials.gov Identifier: NCT00107666
• Other Study ID Numbers: CTI-01-C04-201
• First Posted: Apr 7, 2005
• Last Update Posted: Mar 17, 2006
• Last Verified: Mar 1, 2006

• Keywords provided by , ,: Coronary artery bypass grafting; Heart valve prosthesis implantation; Cardiopulmonary bypass; Oxidative stress; Inflammation; Endotoxemia
• Additional relevant MeSH terms: Coronary Disease; Heart Valve Diseases

Study Results

No Results Posted as of Mar 17, 2006