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

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.

Timeline

Start

2005-04

Primary completion

—

Completion

2006-04

Publications

• Background 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.
• Background 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.
• Background 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. doi: 10.1073/pnas.192222999. Epub 2002 Sep 3.
• Background 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. doi: 10.1016/j.jtcvs.2003.11.032.
• Background Fink MP. Ethyl pyruvate: a novel anti-inflammatory agent. Crit Care Med. 2003 Jan;31(1 Suppl):S51-6. doi: 10.1097/00003246-200301001-00008.

Drugs

Indications