Efficacy of Dexamethasone to Improve Clinical Outcomes in Coronary Artery Bypass Patients

Study Overview
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Brief Summary
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This is a single-center, double-blind, randomized controlled clinical trial comparing four groups: placebo conventional coronary artery bypass graft (CCABG) group, dexamethasone CCABG group, placebo off-pump coronary artery bypass (OPCAB) group, and dexamethasone OPCAB group. The primary outcomes of this study is comprised of presence of arrhythmia, major adverse cardiac events (MACE), myocardial infarction, stroke, renal failure, respiratory failure, inflammation, and death. These primary outcomes were assessed during the surgery, 18 hours post surgery, every day during the hospital stay, 14 days and 30 days post surgery.

Detailed Description
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A single center randomized controlled clinical trial was conducted at Harapan Kita National Cardiovascular Center, Jakarta, Indonesia, as the tertiary cardiovascular referral hospital. The RCT was conducted from July 1st, 2018 to March 31st, 2019 (current status: completed). This study assessed the efficacy of intraoperative high dose dexamethasone administration (1 mg/kg BW, maximum dose 100 mg) in reducing inflammatory response and improving clinical outcome in patients undergoing coronary artery bypass surgery. The study groups consist of placebo CCABG, dexamethasone CCABG, placebo OPCAB, and dexamethasone OPCAB. The subjects were adults indicated to undergo elective coronary artery bypass surgery with no evidence of prior inflammation nor allergic reaction to dexamethasone. Both the patients and the principal investigators were blinded for the treatment-control allocation. The patients were purposively selected and were randomly assigned to one of the arms with block randomization. The primary outcomes of this study is comprised of presence of arrhythmia, major adverse cardiac events (MACE), myocardial infarction, stroke, renal failure, respiratory failure, inflammation, and death. These primary outcomes were assessed during the surgery, 18 hours post surgery, every day during the hospital stay, 14 days and 30 days post surgery. The minimum sample size required for this study was 100 subjects (25 each group).

Official Title
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Efficacy of Dexamethasone to Reduce Inflammatory Response and Improve Clinical Outcome in Coronary Artery Bypass Patients: A Multi Arm, Double Blind, Single Center, Randomized Controlled Trial

Conditions
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Coronary Artery Disease, Inflammatory Response

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Coronary artery disease patients indicated for elective coronary artery bypass surgery Patients aged >18 years old Patients who agreed to participate in this study Exclusion Criteria: Patients with preoperative systemic inflammation evidenced by high axillary temperature (≥38◦C) and high leukocyte count (≥15.000 ul) Patients with chronic arrhythmia Patients who are indicated to undergo other procedures than coronary artery bypass (i.e. valvular repair, septal repair) Patients with history of severe organ dysfunction (class IV congestive heart failure, renal failure, respiratory arrest, and stroke with sequelae) Patients with history of cardiac surgery Patients who takes routine corticosteroids or immunomodulators Patients who are allergic to corticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, single center, multi-arm phase 4 randomized controlled clinical trial was conducted with four intervention arms: placebo CCABG, dexamethasone CCABG, placebo OPCAB, and dexamethasone OPCAB arm. The recruitment of subjects were conducted simultaneously by means of a block randomization.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone CCABG<br>Dexamethasone administered 1 mg per kg body weight (maximum dose 100 mg), given single dose after induction of anesthesia. Surgeon then carried out the conventional coronary artery bypass graft procedure with the use of cardiopulmonary bypass machine. | Drug: Dexamethasone<br>* Administration of intraoperative 1 mg/kg body weight dexamethasone<br>|
| Placebo Comparator: Placebo CCABG<br>Normal saline (NaCl 0.9%) administered 1 mg per kg body weight (maximum dose 100 mg), given single dose after induction of anesthesia. Surgeon then carried out the conventional coronary artery bypass graft procedure with the use of cardiopulmonary bypass machine. | Drug: Normal saline<br>* Placebo (NaCl 0.9%)<br>|
| Active Comparator: Dexamethasone OPCAB<br>Dexamethasone administered 1 mg per kg body weight (maximum dose 100 mg), given single dose after induction of anesthesia. Surgeon then carried out the off-pump coronary artery bypass procedure without the use of cardiopulmonary bypass machine. | Drug: Dexamethasone<br>* Administration of intraoperative 1 mg/kg body weight dexamethasone<br>|
| Placebo Comparator: Placebo OPCAB<br>Normal saline (NaCl 0.9%) administered 1 mg per kg body weight (maximum dose 100 mg), given single dose after induction of anesthesia. Surgeon then carried out the off-pump coronary artery bypass procedure without the use of cardiopulmonary bypass machine. | Drug: Normal saline<br>* Placebo (NaCl 0.9%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of arrhythmia as seen on EKG | New onset of a postoperative rhythm disorder including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, and atrioventricular block | 18 to 24 hours post surgery | 
| Presence of arrhythmia as seen on EKG | New onset of a postoperative rhythm disorder including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, and atrioventricular block | Daily during hospital stay (an average of 7 days) | 
| Perioperative myocardial infarction as seen on EKG | New Q waves or new left bundle branch block on an electrocardiogram, combined with a biomarker (creatine kinase-MB or troponin) >5 times the upper normal limit | 18 to 24 hours post surgery | 
| Perioperative myocardial infarction as seen on EKG | New Q waves or new left bundle branch block on an electrocardiogram, combined with a biomarker (creatine kinase-MB or troponin) >5 times the upper normal limit | Daily during hospital stay (an average of 7 days) | 
| Presence of stroke diagnosed by clinical appearance and CT or MRI | A neurologic deficit lasting more than 24 hours with signs of a new ischemic cerebral infarction on computed tomography or magnetic resonance imaging | Daily during hospital stay (an average of 7 days) | 
| Renal failure as measured by serum creatinine | Increase in postoperative serum creatinine of at least 3-times the preoperative value, or a serum creatinine level >4mg/dL associated with an acute increase in serum creatinine of at leas 0.5mg/dL | 18 to 24 hours post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory reactions | Measurement of interleukin (IL)-6, C-reactive protein (CRP), and procalcitonin | 18 to 24 hours post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexamethasone, arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation