Role of Glutamine as Myocardial Protector in Elective On-Pump CABG Surgery With Low EF

NCT04560309 | Completed Phase 3 Results DMC

• 1 other identifier: LB.02.01/VII/466/KEP059/202
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Coronary artery disease has the highest mortality rate worldwide and coronary artery bypass grafting (CABG) is the most common cardiac surgery performed in patients with coronary artery disease to revascularize the heart. Despite of improvement in operation techniques, cardioplegia, cardiopulmonary bypass (CPB), myocardial injury related to on-pump CABG is still prominent. In patient with low ejection fraction undergone on-pump CABG, myocardial injury is related to worse outcome and prognosis during peri-operative and post-operative period. On-pump CABG patients with low ejection fraction has increased (up to four times higher) post-operative in hospital mortality rate compared to patient with normal ejection fraction. Administration of intravenous glutamine had been documented in reducing myocardial damage during cardiac surgery and previous studies indicated that glutamine can protect against myocardial injury by various mechanism during ischemia and reperfusion. The purpose of this study to determine whether intravenous glutamine could prevent the decline of plasma glutamine level, reduce myocardial damage, improve hemodynamic profile, and reduce morbidity of on-pump CABG in patients with low ejection fraction.

Conditions

Coronary Artery Bypass; Cardiopulmonary Bypass; Coronary Artery Disease

Keywords

Glutamine; Myocardial protection; Coronary artery bypass grafting; Cardiopulmonary bypass; Low ejection fraction; Myocardial injury

Outcome Measures

Primary Outcomes (7)

• Plasma Troponin I at Baseline

  Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL

  Before induction to anesthesia

• Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass

  Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL

  5 minute after cardiopulmonary bypass

• Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass

  Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL

  6 hour after cardiopulmonary bypass

• Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass

  Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL

  24 hour after cardiopulmonary bypass

• Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass

  Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL

  48 hour after cardiopulmonary bypass

• Plasma Glutamine at Baseline

  Plasma glutamine were measured using colorimetric tests in unit of µmol/L

  Before induction to anesthesia

• Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass

  Plasma glutamine were measured using colorimetric tests in unit of µmol/L

  24 hour after cardiopulmonary bypass

Secondary Outcomes (15)

• Right Atrial Appendage Alpha-ketoglutarate

  5 minute after cardiopulmonary bypass

• Right Atrial Appendage Myocardial Injury Score

  5 minute after cardiopulmonary bypass

• Right Atrial Appendage Apoptosis Index

  5 minute after cardiopulmonary bypass

• Anti Cardiac Troponin I Expression

  5 minute after cardiopulmonary bypass

• Ejection Fraction

  Immediately after induction of anesthesia

Other Outcomes (4)

• Coronary Graft

  Intraoperative

• Total Surgical Procedure Time

  Intraoperative

• Cardiopulmonary Bypass Time

  Intraoperative

Study Arms (2)

Glutamine

EXPERIMENTAL

Intravenous L-alanyl-L-glutamine 0.5 mg/kgbw

Drug: L-alanyl-L-glutamine dipeptide

Control

PLACEBO COMPARATOR

Intravenous NaCl 0.9%

Drug: Placebo

Interventions

L-alanyl-L-glutamine dipeptide DRUG

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.

Also known as: Dipeptiven

Glutamine

Placebo DRUG

Intravenous infusion of 500 mL normal saline, started after induction of anesthesia for 24 hours.

Also known as: Normal saline

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cardiovascular Center Harapan Kita Hospital Indonesia: lead

Study Sites (1)

National Cardiovascular Center Harapan Kita Hospital Indonesia

Jakarta, 11420, Indonesia

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

alanylglutamine; Saline Solution

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

This study has some limitations. Limitations includes the sampling time of right atrial appendage tissue which was only at 5 minutes after CPB. Right atrial appendage tissue was used for apoptotic index assessment using TUNEL staining. Right atrial appendage tissue could not be sampled at 6 hours after CPB because sternal closure was performed prior to 6 hours.

Results Point of Contact

• Title: I Made Adi Parmana, M.D.
• Organization: Nationcal Cardiovascular Center Harapan Kita

adiparmana13@gmail.com

+62 812-4601-212

Study Officials

• I Made Adi Parmana

  National Cardiovascular Center Harapan Kita Indonesia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 23, 2020
• Study Start: January 1, 2021
• Primary Completion: October 30, 2021
• Study Completion: November 23, 2021
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available after publication until 36 months following article publication
• Access Criteria: Researchers needs to state their aims of analyses and provide a methodologically sound proposal. Proposals should be directed to the corresponding author.

Locations

ID (1)