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

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT05487508

Collaborator

(none)

120

Enrollment

Location

Arms

Actual Duration (Months)

13.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Inflammatory Response	Drug: Dexamethasone Drug: Normal saline	Phase 4

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Investigator)

Masking Description:

Double (Participant, Investigator) Participants were not aware of the arms/treatment given as they were under general anesthesia during the administration of dexamethasone. Preoperatively, subjects were given explanation of the purpose, methods, benefits, and risks of the procedure including the randomization method. Investigators were kept unaware of the randomization of dexamethasone as they were restricted for assessing the patients' medical record and the patients' identity were coded in the primary database

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2018

Actual Primary Completion Date :

Jan 31, 2019

Actual Study Completion Date :

Mar 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dexamethasone CCABG 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 Administration of intraoperative 1 mg/kg body weight dexamethasone
Placebo Comparator: Placebo CCABG 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 Placebo (NaCl 0.9%)
Active Comparator: Dexamethasone OPCAB 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 Administration of intraoperative 1 mg/kg body weight dexamethasone
Placebo Comparator: Placebo OPCAB 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 Placebo (NaCl 0.9%)

Outcome Measures

Primary Outcome Measures

Presence of arrhythmia as seen on EKG [18 to 24 hours post surgery]
New onset of a postoperative rhythm disorder including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, and atrioventricular block
Presence of arrhythmia as seen on EKG [Daily during hospital stay (an average of 7 days)]
New onset of a postoperative rhythm disorder including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, and atrioventricular block
Perioperative myocardial infarction as seen on EKG [18 to 24 hours post surgery]
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
Perioperative myocardial infarction as seen on EKG [Daily during hospital stay (an average of 7 days)]
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
Presence of stroke diagnosed by clinical appearance and CT or MRI [Daily during hospital stay (an average of 7 days)]
A neurologic deficit lasting more than 24 hours with signs of a new ischemic cerebral infarction on computed tomography or magnetic resonance imaging
Renal failure as measured by serum creatinine [18 to 24 hours post surgery]
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

Secondary Outcome Measures

Inflammatory reactions [18 to 24 hours post surgery]
Measurement of interleukin (IL)-6, C-reactive protein (CRP), and procalcitonin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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