Impact of Perioperative Treatment With Intravenous Glutamine on Myocardial Protection in Cardiac Surgery Patients With Aortic Stenosis

The purpose of this study is to confirm if myocardial protection effect can be obtained by intravenous administration of glutamine in patients undergoing aortic valve replacement with severe aortic stenosis (who are at high risk for ischemia-reperfusion injury). As a prospective double blinded randomized placebo-controlled trial, the investigators detect and compare the degree of myocardial damage(with CK-MB and Troponin T) and myocardial protection (through hsp 70 expression in atrial tissue), cardiovascular index, inflammatory reaction, and clinical manifestation.

Study Overview

• Status: Unknown
• Conditions: Aortic Valve Stenois
• Intervention / Treatment: Drug: N(2)-L-Alanine L-Glutamine dipeptide; Drug: placebo (0.9% NaCl (normal saline))

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jong Wook Song, MD; Phone Number: 82-2-2227-3971; Email: SJW72331@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine
    • Contact: Jong Wook Song, MD; Phone Number: 82-2-2227-3971; Email: SJW72331@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with between 20 and 80 years scheduled for aortic valve replacement alone or combined surgery including aortic valve replacement due to severe aortic valve stenosis

Exclusion Criteria:

• Patients with renal insufficiency (eGFR 60 ml / min / 1.73 m 2 or less)
• patients who are considering surgery for coronary artery disease or who have a stenosis> 70%
• hemodynamically unstable patients undergoing emergency surgery or patients with intra-aortic balloon pump insertion
• patients unable to make their own decisions, illiterate, foreigners
• epilepsy
• severe metabolic acidosis
• pulmonary edema
• history of myocardial infarction
• elevation of total bilirubin or AST / ALT
• Patients higher than normal, weighing more than 80 kg
• with evidence of infection
• pregnant and lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: placebo (0.9% NaCl (normal saline)); Intravenous infusion of 0.9% NaCl for 8 hours before induction of anesthesia(rate=2.5*weight/8 ml/h) and administration 0.9% NaCl into the central vein for 10 hours after induction of anesthesia(rate=0.75*weight ml/h)
EXPERIMENTAL: Glutamine; Intravenous glutamine infusion perioperatively for 18 hours (8 hours before surgery and 10 hours after induction of anesthesia)	Drug: N(2)-L-Alanine L-Glutamine dipeptide; :Intravenous infusion of N (2) -L-alanyl-L-glutamine(mixed with normal saline, ratio 1:1) at the dose of 0.25g/kg(body weight) for 8 hours before induction of anesthesia(rate=2.5*weight/8 ml/h) and administration another 0.25g/kg(body weight) of N (2) -L-alanyl-L-glutamine(mixed with 8.5% amino acid solution, ratio 1:5) into the central vein for 10 hours after induction of anesthesia(rate=0.75*weight ml/h)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
degree of myocardial damage with CK-MB (Creatine Kinase MB lsoenzyme)	1 day before the operation
degree of myocardial damage with CK-MB (Creatine Kinase MB lsoenzyme)	10 minutes after ICU(intensive care unit) entrance,
degree of myocardial damage with CK-MB (Creatine Kinase MB lsoenzyme)	24 hours after surgery
degree of myocardial damage with CK-MB (Creatine Kinase MB lsoenzyme)	48 hours after surgery
Troponin-T(Tn-T) level	1 day before the operation
Troponin-T(Tn-T) level	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-6		a day before surgery
IL-6		10 minutes after ICU(intensive care unit) entrance
Free fatty acid		a day before surgery
Free fatty acid		10 minutes after ICU(intensive care unit) entrance
CRP		a day before surgery
CRP		24 hours after surgery
cardiovascular index		10 minutes after ICU(intensive care unit) entrance
cardiovascular index		12 hours after surgery
cardiovascular index		24 hours after surgery
occurrence of sternal infections		Within 30 days postoperatively
mortality		During hospitalization regardless of length of stay or within 30 days of surgery if discharged
occurrence of cardiovascular complications	*cardiovascular (myocardial infarction, heart failure, arrhythmia), cerebral infarction, renal failure: During the hospitalization for surgery, which includes the entire postoperative period up to discharge, even if over 30 days	up to 1 year

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 20, 2018
• Primary Completion (ANTICIPATED): September 28, 2019
• Study Completion (ANTICIPATED): September 28, 2019

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: November 9, 2017
• First Posted (ACTUAL): November 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: 4-2017-0774

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No