Trial of Cyclosporine for Myocardial Protection During Open Heart Surgery (CYCLO1)

A Randomized Trial of Cyclosporine for Myocardial Protection During Open Heart Surgery

Administration of cyclosporine has been found to have a myocardial protective effect, improving post-operative cardiac function in patients undergoing percutaneous coronary interventions by diminishing infarct size. The purpose of the proposed study is to conduct a randomized, controlled clinical trial in patients undergoing isolated valvular heart surgery, or coronary artery bypass surgery. Specifically the investigators will evaluate the cardio-protective effects of cyclosporine on post ischemic-arrest myocardium. The two factors will be treatment group and cyclosporine versus placebo.

Study Overview

• Status: Terminated
• Conditions: Cardiac Surgical Procedures
• Intervention / Treatment: Drug: cyclosporine; Drug: saline solution

Detailed Description

The specific aim of this study is to perform a randomized controlled study to compare the effects of cyclosporine v. placebo on changes in myocardial functioning associated with open heart surgery for isolated valvular or coronary artery bypass procedures.

The research question is:

Compared to placebo, does administration of cyclosporine just before surgery improve myocardial functioning in terms of:

• Transthoracic ECHO (TTE) assessment of ejection fraction
• Cardiac index (CI), mixed venous oxygen saturation (SVO2), systemic vascular resistance (SVR)
• Length of stay
• 30-d mortality
• Angina Scale
• SF-36 measure of quality of life

• Measures associated with myocardial function:

  1. Cardiac Index
  2. Blood glucose level
  3. Serum Troponin I level
  4. Free Fatty Acid levels
  5. Serum CPK-MB levels
  6. Serum phosphoratase levels

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Medical School Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Men and women, 18 years of age or older
• Patients with multi-vessel coronary artery disease
• Patients undergoing isolated valvular heart surgery (aortic/ mitral)
• Patients undergoing CABG

Exclusion Criteria:

• Patients with cardiac arrest
• Patients with ventricular fibrillation
• Patients with cardiogenic shock
• Patients requiring circulatory arrest
• Patients with known hypersensitivity to cyclosporine
• Patients with known renal failure or a GFR <50 ml/min/1.732
• Patients with liver failure
• Patients with uncontrolled hypertension
• Women who are pregnant or who are of childbearing age and not on contraception
• Patients with a serum bilirubin level greater than 3 mg/100 mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporine; Cyclosporine Group: Patients will receive a dose of cyclosporine just after they are heparinized. They will receive 2.5 mg of cyclosporine (Sandimmune, Novartis) per kilogram of body weight. It will be injected into a central venous line at the time the central venous line is inserted by the anesthesia team.	Drug: cyclosporine; Cyclosporine Patients will receive a dose of cyclosporine just after they are heparinized. They will receive 2.5 mg of cyclosporine (Sandimmune, Novartis) per kilogram of body weight. It will be injected into a central venous line at the time the central venous line is inserted by the anesthesia team.
Placebo Comparator: Placebo; Placebo: Patients will undergo the cardiac surgery procedures using standard technique. They will have ischemic arrest of the heart with cold blood cardioplegia using standardized methods of myocardial protection or off-pump CABG. The patients in the placebo group will receive a volumetrically equivalent dose of normal saline to the cyclosporine dose.	Drug: saline solution; Placebo Group: Patients will undergo the cardiac surgery procedures using standard technique. They will have ischemic arrest of the heart with cold blood cardioplegia using standardized methods of myocardial protection or off-pump CABG. The patients in the placebo group will receive a volumetrically equivalent dose of normal saline to the cyclosporine dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Length of Stay (LOS)	postoperative to 30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Left Ventricular Ejection Fraction (TTE)	postoperative
Cardiac Index	postoperative
SVO2	Postoperative
Systemic Vascular Resistance (SVR)	postoperative

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Jon-Cecil M Walkes, MD, University of Texas Medical School Houston; Study Director: Heinrich Taegtmeyer, MD, University of Texas Medical School Houston; Study Chair: George K Goodrick, PhD, University of Texas Medical School Houston

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: October 5, 2009
• First Submitted That Met QC Criteria: October 6, 2009
• First Posted (Estimate): October 7, 2009

Study Record Updates

• Last Update Posted (Estimate): November 2, 2010
• Last Update Submitted That Met QC Criteria: November 1, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: cyclosporine; open heart surgery; myocardial protection
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CYCLO1