Clinical trial NCT00107666: CTI-01 (Ethyl Pyruvate) Safety and Complication Prevention in Cardiac Surgery Patients on Cardiopulmonary Bypass (CPB)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coronary Disease
Heart Valve Diseases
Keywords: Coronary artery bypass grafting
Heart valve prosthesis implantation
Cardiopulmonary bypass
Oxidative stress
Inflammation
Endotoxemia
Lead sponsor: Critical Therapeutics
Sponsor class: INDUSTRY
First posted: 2005-04-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Death
measure: Composite morbidity endpoint
Secondary outcomes:
measure: Respiratory dysfunction
measure: Cardiac dysfunction
measure: Renal dysfunction
measure: Gastrointestinal dysfunction
measure: Mental status
measure: Length of ICU (Intensive Care Unit)/hospital stay
Other outcomes:
Locations:
city: Laguna Hills
country: United States
facility: Saddleback Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Wichita
country: United States
facility: Research Support Personnel
state: Kansas
city: Salisbury
country: United States
facility: Peninsula Regional Medical Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University - Brody School of Medicine
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital - The Cardiovasular Center
state: Pennsylvania
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital/Texas Heart Institute
state: Texas
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - VA Medical Center
state: Wisconsin
Study officials:
affiliation: Critical Therapeutics Incorporated
name: Walter Newman, Ph.D.
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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. doi: 10.1073/pnas.192222999. Epub 2002 Sep 3.
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. doi: 10.1016/j.jtcvs.2003.11.032.
citation: 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.