- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04560309
Role of Glutamine as Myocardial Protector in Elective On-Pump CABG Surgery With Low EF
Role of Glutamine as Myocardial Protector in Elective On-Pump Coronary Artery Bypass Graft Surgery With Low Ejection Fraction
Study Overview
Status
Intervention / Treatment
Detailed Description
The study was a double-blind randomized controlled trial to assess the role of glutamine as a myocardial protection during coronary artery bypass grafting under cardiopulmonary bypass in patients with left ventricle ejection fraction of 31-50%. This study was approved by Institutional Review Board of National Cardiovascular Center Harapan Kita and informed consent was obtained before randomization for patient eligible for this study. Allocation of participant to the treatment group was done by block randomization by staff who was not involved in the study. The intervention drug was prepared by pharmacist who also was not involved in the study. Glutamine solution was supplied as L-alanyl-L-glutamine dipeptide (Dipeptiven, 200 mg/mL, Fresenius Kabi, Bad Homburg, Germany) and was prepared to contain 0.5gr/kgbw glutamine diluted in NaCl 0.9% to a final volume of 500 mL. Placebo was supplied as 500 ml of NaCl 0.9%, prepared in similar fashion and packaging as glutamine solution. Principal investigator, care provider, outcome assessor, and participant were blinded to the assigned group until after the end of the study.
Baseline participant characteristics were collected before the intervention included age, sex, body weight, body height, body mass index, and documented pre-operative left ventricle ejection fraction. Coronary artery bypass grafting and cardiopulmonary bypass was done in concordance to standard operating procedure in National Cardiovascular Center Harapan Kita, followed by transit time flow meter measurement to ensure quality of the graft. Modifying factor of the study, the investigators measured duration of surgery, duration of cardiopulmonary bypass, and duration of aortic cross clamp.
The primary outcome of the study was plasma troponin I level. The investigators anticipated plasma troponin I level difference of 20% with standard deviation of 0.04 ng/mL, and for statistical power of 80% and level of significance of 0.05, the required sample size was 24.5 participants per group. As anticipation for participant drop out, the investigators planned to recruit a total of 60 participants.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Jakarta, Indonesia, 11420
- National Cardiovascular Center Harapan Kita Hospital Indonesia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with coronary heart disease indicated for elective coronary artery bypass grafting under cardiopulmonary bypass
- Patients with left ventricle ejection fraction 31% -50% confirmed by echocardiography or radio nuclear study.
- Patients age ≥18 years
- Never had heart surgery before
- Agree to participate in the study and signed informed consent
Exclusion Criteria:
- Emergency coronary artery grafting bypass
- Having additional procedures other than coronary artery bypass grafting
- History of myocardial infarction with onset less than 3 months
- Patients with serum creatinine level more than 2 g/dL
- Patients with ALT/AST levels more than 1.5 times the upper limit of normal value
- Required to use intra-aortic balloon pump pre-operatively
- History of stroke with onset less than 3 months
- History of pre-operative atrial fibrillation
- History of heart conduction problem and/or using a pacemaker
- Patients with HIV
- Contraindications to pulmonary artery catheter insertion
Drop out Criteria
- Experiencing stroke after surgery
- Experiencing surgery related complication (haemorrhage) requiring re operation
- Requiring continuous veno-venous hemofiltration or haemodialysis after surgery
- Delayed sternal closure
- Aortic cross clamp duration more than 120 minutes and/or cardiopulmonary bypass time more than 180 minutes
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Glutamine
Intravenous L-alanyl-L-glutamine 0.5 mg/kgbw
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Intravenous infusion of 0.5 mg/kgbw L-alanyl-L-glutamine dipeptide diluted in normal saline to volume of 500 mL, started after induction of anesthesia for 24 hours.
Other Names:
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Placebo Comparator: Control
Intravenous NaCl 0.9%
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Intravenous infusion of 500 mL normal saline, started after induction of anesthesia for 24 hours.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Troponin I at Baseline
Time Frame: Before induction to anesthesia
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Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
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Before induction to anesthesia
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Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass
Time Frame: 5 minute after cardiopulmonary bypass
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Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
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5 minute after cardiopulmonary bypass
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Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass
Time Frame: 6 hour after cardiopulmonary bypass
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Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
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6 hour after cardiopulmonary bypass
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Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass
Time Frame: 24 hour after cardiopulmonary bypass
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Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
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24 hour after cardiopulmonary bypass
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Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass
Time Frame: 48 hour after cardiopulmonary bypass
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Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
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48 hour after cardiopulmonary bypass
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Plasma Glutamine at Baseline
Time Frame: Before induction to anesthesia
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Plasma glutamine were measured using colorimetric tests in unit of µmol/L
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Before induction to anesthesia
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Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass
Time Frame: 24 hour after cardiopulmonary bypass
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Plasma glutamine were measured using colorimetric tests in unit of µmol/L
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24 hour after cardiopulmonary bypass
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Right Atrial Appendage Alpha-ketoglutarate
Time Frame: 5 minute after cardiopulmonary bypass
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Right atrial appendage alpha-ketoglutarate were measured from right atrial appendage tissue biopsy using colorimetric tests in unit of g/mol.
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5 minute after cardiopulmonary bypass
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Right Atrial Appendage Myocardial Injury Score
Time Frame: 5 minute after cardiopulmonary bypass
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Right atrial appendage myocardial injury score were measured from tissue section stained with hematoxylin-eosin and examined under by light microscopy in score of 0 (no change) to 3 (major changes with necrosis and diffuse inflammation).
Higher scores mean worse outcome
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5 minute after cardiopulmonary bypass
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Right Atrial Appendage Apoptosis Index
Time Frame: 5 minute after cardiopulmonary bypass
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Right atrial appendage apoptosis index were measured from tissue section stained with in situ terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and examined under light microscopy in average number of apoptotic cells (positively stained) from 6 random fields per section
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5 minute after cardiopulmonary bypass
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Anti Cardiac Troponin I Expression
Time Frame: 5 minute after cardiopulmonary bypass
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Right atrial appendage anti cardiac troponin I expression were measured from tissue section stained with anti-cardiac troponin I antibody and examined under light microscopy in score of 0 (no change) to -3 (no area observed with anti-cardiac troponin I expression).
Higher score mean better outcome
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5 minute after cardiopulmonary bypass
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Ejection Fraction
Time Frame: Immediately after induction of anesthesia
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Ejection fraction were measured by transesophageal echocardiography using Simpson method in percentage (%)
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Immediately after induction of anesthesia
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Ejection Fraction
Time Frame: 5 minutes after cardiopulmonary bypass
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Ejection fraction were measured by transesophageal echocardiography using Simpson method in percentage (%)
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5 minutes after cardiopulmonary bypass
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Cardiac Index
Time Frame: Immediately after induction of anesthesia, 5 minute, 2 hour, 6 hour, 24 hour after cardiopulmonary bypass
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Cardiac index were measured from pulmonary artery catheter using thermodilution method in unit of L/min/m^2
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Immediately after induction of anesthesia, 5 minute, 2 hour, 6 hour, 24 hour after cardiopulmonary bypass
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Plasma Lactate Before Induction to Anesthesia
Time Frame: Before induction to anesthesia
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Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
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Before induction to anesthesia
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Plasma Lactate 5 Minute After Cardiopulmonary Bypass
Time Frame: 5 minute after cardiopulmonary bypass
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Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
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5 minute after cardiopulmonary bypass
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Plasma Lactate 6 Hours After Cardiopulmonary Bypass
Time Frame: 6 hours after cardiopulmonary bypass
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Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
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6 hours after cardiopulmonary bypass
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Plasma Lactate 24 Hours After Cardiopulmonary Bypass
Time Frame: 24 hours after cardiopulmonary bypass
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Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
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24 hours after cardiopulmonary bypass
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Plasma Lactate 48 Hours After Cardiopulmonary Bypass
Time Frame: 48 hours after cardiopulmonary bypass
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Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
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48 hours after cardiopulmonary bypass
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Intensive Care Unit Ventilation Time
Time Frame: 28 days (or until hospital discharge)
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Intensive care unit ventilation time were measured from length of time participant was on ventilator in intensive care unit in minutes.
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28 days (or until hospital discharge)
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Intensive Care Unit Length of Stay
Time Frame: 28 days (or until hospital discharge)
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Intensive care unit length of stay were measured from length of time participant spent in intensive care unit in unit of hours
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28 days (or until hospital discharge)
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Vasoactive Inotropic Score
Time Frame: 28 days (or until hospital discharge)
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Vasoactive inotropic score (VIS) were maximum vasoactive and inotropic dose required by participant after surgery measured by VIS=dopamine dose in mg/kgbw/min + dobutamine dose in mg/kgbw/min + 100 x epinephrine dose in mg/kgbw/min + 10 x milrinone dose in mcg/kgbw/min + 10.000 x vasopressin dose in units/kgbw/min + 100 x norepinephrine dose in mcg/kgbw/min.
Higher scores means worse outcomes.
VIS >= 20 is considered as high VIS and is associated with poor outcomes.
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28 days (or until hospital discharge)
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Coronary Graft
Time Frame: Intraoperative
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Number of coronary arteries grafted during operation
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Intraoperative
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Total Surgical Procedure Time
Time Frame: Intraoperative
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Total time taken for the surgical procedure.
Measured in minutes.
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Intraoperative
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Cardiopulmonary Bypass Time
Time Frame: Intraoperative
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Total time measured the patient went under cardiopulmonary bypass.
Measured in minutes.
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Intraoperative
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Aortic Cross-clamping Time
Time Frame: Intraoperative
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Total time the patient underwent aortic cross-clamping during the surgical procedure.
Measured in minutes.
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Intraoperative
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Collaborators and Investigators
Investigators
- Principal Investigator: I Made Adi Parmana, National Cardiovascular Center Harapan Kita Indonesia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- LB.02.01/VII/466/KEP059/202 (Other Identifier: National Cardiovascular Center Harapan Kita Indonesia)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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