Glutamate for Metabolic Intervention in Coronary Surgery

NCT00489827 | Completed Phase 3 Results DMC

• 3 other identifiers: 151:2003/7040320030595M76-05
• Study Type: interventional
• Target: 865
• Locations: 1 country
• Sites: 3

Brief Summary

The main purpose of this study is to determine whether intravenous glutamate infusion given in association with surgery for unstable coronary artery disease can protect the heart from myocardial injury, postoperative heart failure and death.

Conditions

Coronary Artery Bypass; Myocardial Ischemia; Myocardial Infarction; Coronary Artery Disease

Keywords

Coronary Artery Bypass; Myocardial Protection; Angina, Unstable; Myocardial Ischemia; Myocardial Infarction; Unstable Coronary Artery Disease; Glutamate

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Perioperative Myocardial Infarction, Postoperative Heart Failure or Postoperative Mortality

  30 days

Secondary Outcomes (10)

• Degree of Perioperative Myocardial Injury

  perioperative

• Postoperative Hemodynamic State

  Until arrival to ICU

• Postoperative Hemodynamic State in Patients With Severely Reduced Left Ventricular Ejection Fraction (LVEF<0.40)

  End of surgery

• Postoperative Renal Function

  30 days

• Number of Participants With Postoperative Stroke < 24 Hours

  24 hours

Study Arms (2)

Intravenous glutamate

ACTIVE COMPARATOR

Intravenous infusion of 0.125 M glutamic acid solution at a rate of 1.65 ml/hour and kg body weight beginning with institution of anesthesia and stopping 2 hours after unclamping of aorta in patients operated for unstable coronary artery disease.

Other: Intravenous glutamate infusion

Saline infusion

PLACEBO COMPARATOR

Intravenous infusion of saline at a rate of 1.65 ml/hour and kg body weight beginning with institution of anesthesia and stopping 2 hours after unclamping of aorta in patients operated for unstable coronary artery disease.

Drug: Intravenous infusion of saline

Interventions

Intravenous infusion of saline DRUG

Intravenous infusion of isotonic saline at a rate of 1.65 ml/hour and kg body weight beginning with institution of anesthesia and stopping 2 hours after unclamping of aorta in patients operated for unstable coronary artery disease.

Saline infusion

Intravenous glutamate infusion OTHER

Intravenous infusion of 0.125 M glutamic acid solution at a rate of 1.65 ml/hour and kg body weight beginning with institution of anesthesia and stopping 2 hours after unclamping of aorta in patients operated for unstable coronary artery disease.

Intravenous glutamate

Eligibility Criteria

• Age: Up to 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• surgery for unstable coronary artery disease (unstable angina, non-STEMI)
• accepted for surgery \< 2 weeks after STEMI
• coronary surgery for indications above performed with or without cardiopulmonary bypass
• coronary surgery for indications above with or without simultaneous valve procedure

You may not qualify if:

• informed consent not possible because of critical condition or other reason
• preoperative use of inotropes or mechanical circulatory assist
• preoperative dialysis
• redo-procedure
• unexpected intraoperative finding / event that increased the dignity of the procedure to overshadow the originally planned operation
• body weight \> 125 kg
• food allergy known to have caused flush, rash or asthma

Sponsors & Collaborators

• University Hospital, Linkoeping: lead
• Region Örebro County: collaborator
• Blekingesjukhuset, Karlskrona: collaborator

Study Sites (3)

Blekingesjukhuset, Karlskrona

Karlskrona, SE-371 85, Sweden

Location

University Hospital, Linköping

Linköping, SE-581 85, Sweden

Location

University Hospital, Örebro

Örebro, SE 701 85, Sweden

Location

Related Publications (34)

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• Dahlin LG, Olin C, Svedjeholm R. Perioperative myocardial infarction in cardiac surgery--risk factors and consequences. A case control study. Scand Cardiovasc J. 2000 Oct;34(5):522-7. doi: 10.1080/140174300750064710.

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• Pisarenko OI, Baranov AV, Aleshin OI, Studneva IM, Pomerantsev EA, Nikolaeva LF, Savchenko AP, Pavlov NA. Features of myocardial metabolism of some amino acids and ammonia in patients with coronary artery disease. Eur Heart J. 1989 Mar;10(3):209-17. doi: 10.1093/oxfordjournals.eurheartj.a059468.

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• Thomassen A, Nielsen TT, Bagger JP, Pedersen AK, Henningsen P. Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X. Am J Cardiol. 1991 Aug 1;68(4):291-5. doi: 10.1016/0002-9149(91)90821-2.

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• Thomassen AR. Myocardial uptake and effects of glutamate during non-ischaemic and ischaemic conditions. A clinical study with special reference to possible interrelationships between glutamate and myocardial utilization of carbohydrate substrates. Dan Med Bull. 1992 Dec;39(6):471-88. No abstract available.

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  PMID: 1405674 BACKGROUND

• Pisarenko OI, Portnoy VF, Studneva IM, Arapov AD, Korostylev AN. Glutamate-blood cardioplegia improves ATP preservation in human myocardium. Biomed Biochim Acta. 1987;46(6):499-504.

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• Suleiman MS, Fernando HC, Dihmis WC, Hutter JA, Chapman RA. A loss of taurine and other amino acids from ventricles of patients undergoing bypass surgery. Br Heart J. 1993 Mar;69(3):241-5. doi: 10.1136/hrt.69.3.241.

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• Kimose HH, Ravkilde J, Helligso P, Knudsen MA, Thomassen AR, Nielsen TT, Djurhuus JC. Myocardial loss of glutamate after cold chemical cardioplegia and storage in isolated blood-perfused pig hearts. Thorac Cardiovasc Surg. 1993 Apr;41(2):93-100. doi: 10.1055/s-2007-1013829.

  PMID: 8103947 BACKGROUND

• Smith RC, Leung JM, Mangano DT. Postoperative myocardial ischemia in patients undergoing coronary artery bypass graft surgery. S.P.I. Research Group. Anesthesiology. 1991 Mar;74(3):464-73. doi: 10.1097/00000542-199103000-00013.

  PMID: 2001026 BACKGROUND

• Pisarenko OI, Lepilin MG, Ivanov VE. Cardiac metabolism and performance during L-glutamic acid infusion in postoperative cardiac failure. Clin Sci (Lond). 1986 Jan;70(1):7-12. doi: 10.1042/cs0700007.

  PMID: 2867848 BACKGROUND

• Svedjeholm R, Ekroth R, Joachimsson PO, Ronquist G, Svensson S, Tyden H. Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations. J Thorac Cardiovasc Surg. 1991 Apr;101(4):688-94.

  PMID: 2008107 BACKGROUND

• Svedjeholm R, Vanhanen I, Hakanson E, Joachimsson PO, Jorfeldt L, Nilsson L. Metabolic and hemodynamic effects of intravenous glutamate infusion early after coronary operations. J Thorac Cardiovasc Surg. 1996 Dec;112(6):1468-77. doi: 10.1016/S0022-5223(96)70005-3.

  PMID: 8975838 BACKGROUND

• Vanhanen I, Hakanson E, Jorfeldt L, Svedjeholm R. Intravenous aspartate infusion after a coronary operation: effects on myocardial metabolism and hemodynamic state. Ann Thorac Surg. 1998 May;65(5):1296-302. doi: 10.1016/s0003-4975(98)00155-6.

  PMID: 9594855 BACKGROUND

• Vanhanen I, Svedjeholm R, Hakanson E, Joachimsson PO, Jorfeldt L, Nilsson L, Vanky F. Assessment of myocardial glutamate requirements early after coronary artery bypass surgery. Scand Cardiovasc J. 1998;32(3):145-52. doi: 10.1080/14017439850140102.

  PMID: 9764429 BACKGROUND

• Vanhanen I, Hakanson E, Jorfeldt L, Svedjeholm R. Myocardial uptake and release of substrates in patients operated for unstable angina: impact of glutamate infusion. Scand Cardiovasc J. 2003 May;37(2):113-20. doi: 10.1080/14017430310001230.

  PMID: 12775312 BACKGROUND

• Svedjeholm R, Hakanson E, Szabo Z, Vanky F. Neurological injury after surgery for ischemic heart disease: risk factors, outcome and role of metabolic interventions. Eur J Cardiothorac Surg. 2001 May;19(5):611-8. doi: 10.1016/s1010-7940(01)00664-9.

  PMID: 11343941 BACKGROUND

• Svedjeholm R, Hakanson E, Vanhanen I. Rationale for metabolic support with amino acids and glucose-insulin-potassium (GIK) in cardiac surgery. Ann Thorac Surg. 1995 Feb;59(2 Suppl):S15-22. doi: 10.1016/0003-4975(94)00917-v.

  PMID: 7840694 BACKGROUND

• Rau EE, Shine KI, Gervais A, Douglas AM, Amos EC 3rd. Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion. Am J Physiol. 1979 Jun;236(6):H873-9. doi: 10.1152/ajpheart.1979.236.6.H873. No abstract available.

  PMID: 443452 BACKGROUND

• Engelman RM, Rousou JA, Flack JE 3rd, Iyengar J, Kimura Y, Das DK. Reduction of infarct size by systemic amino acid supplementation during reperfusion. J Thorac Cardiovasc Surg. 1991 May;101(5):855-9.

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• Lazar HL, Buckberg GD, Manganaro AJ, Becker H, Maloney JV Jr. Reversal of ischemic damage with amino acid substrate enhancement during reperfusion. Surgery. 1980 Nov;88(5):702-9.

  PMID: 7434210 BACKGROUND

• Bittl JA, Shine KI. Protection of ischemic rabbit myocardium by glutamic acid. Am J Physiol. 1983 Sep;245(3):H406-12. doi: 10.1152/ajpheart.1983.245.3.H406.

  PMID: 6137148 BACKGROUND

• Haas GS, DeBoer LW, O'Keefe DD, Bodenhamer RM, Geffin GA, Drop LJ, Teplick RS, Daggett WM. Reduction of postischemic myocardial dysfunction by substrate repletion during reperfusion. Circulation. 1984 Sep;70(3 Pt 2):I65-74.

  PMID: 6430593 BACKGROUND

• Pisarenko OI, Solomatina ES, Studneva IM, Ivanov VE, Kapelko VI, Smirnov VN. Protective effect of glutamic acid on cardiac function and metabolism during cardioplegia and reperfusion. Basic Res Cardiol. 1983 Sep-Oct;78(5):534-43. doi: 10.1007/BF01906464.

  PMID: 6140002 BACKGROUND

• Holm J, Vanky F, Svedjeholm R. Association of Glutamate Infusion With Risk of Acute Kidney Injury After Coronary Artery Bypass Surgery: A Pooled Analysis of 2 Randomized Clinical Trials. JAMA Netw Open. 2024 Jan 2;7(1):e2351743. doi: 10.1001/jamanetworkopen.2023.51743.

  PMID: 38252440 DERIVED

• Jiang H, Holm J, Friberg O, Vanky F, Vidlund M, Tajik B, Yang Y, Svedjeholm R. Utility of NT-proBNP as an objective marker of postoperative heart failure after coronary artery bypass surgery: a prospective observational study. Perioper Med (Lond). 2021 Jul 13;10(1):21. doi: 10.1186/s13741-021-00194-4.

  PMID: 34253255 DERIVED

• Jiang H, Holm J, Vidlund M, Vanky F, Friberg O, Yang Y, Svedjeholm R. The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery: a randomized study. J Transl Med. 2020 May 11;18(1):193. doi: 10.1186/s12967-020-02351-7.

  PMID: 32393387 DERIVED

• Vidlund M, Tajik B, Hakanson E, Friberg O, Holm J, Vanky F, Svedjeholm R. Post hoc analysis of the glutamics-trial: intravenous glutamate infusion and use of inotropic drugs after cabg. BMC Anesthesiol. 2016 Aug 2;16(1):54. doi: 10.1186/s12871-016-0216-z.

  PMID: 27484576 DERIVED

• Holm J, Vidlund M, Vanky F, Friberg O, Hakanson E, Walther S, Svedjeholm R. EuroSCORE II and N-terminal pro-B-type natriuretic peptide for risk evaluation: an observational longitudinal study in patients undergoing coronary artery bypass graft surgery. Br J Anaesth. 2014 Jul;113(1):75-82. doi: 10.1093/bja/aeu088. Epub 2014 Apr 11.

  PMID: 24727704 DERIVED

• Holm J, Vidlund M, Vanky F, Friberg O, Hakanson E, Svedjeholm R. Preoperative NT-proBNP independently predicts outcome in patients with acute coronary syndrome undergoing CABG. Scand Cardiovasc J Suppl. 2013 Feb;47(1):28-35. doi: 10.3109/14017431.2012.731518. Epub 2012 Oct 10.

  PMID: 22989031 DERIVED

• Vidlund M, Holm J, Hakanson E, Friberg O, Sunnermalm L, Vanky F, Svedjeholm R. The S-100B substudy of the GLUTAMICS trial: glutamate infusion not associated with sustained elevation of plasma S-100B after coronary surgery. Clin Nutr. 2010 Jun;29(3):358-64. doi: 10.1016/j.clnu.2009.09.007. Epub 2009 Oct 22.

  PMID: 19853332 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia; Myocardial Infarction; Coronary Artery Disease; Angina, Unstable

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Rolf Svedjeholm
• Organization: Dept Cardiothoracic Surgery, Linköping University Hospital, SE58185 Linköping, Sweden

rolf.svedjeholm@regionostergotland.se

+46101034825

Study Officials

• Rolf Svedjeholm, MD PhD

  University Hospital, Linkoeping

  STUDY DIRECTOR

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 19, 2007
• First Posted: June 21, 2007
• Study Start: October 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: August 1, 2022
• Last Updated: May 22, 2024
• Results First Posted: June 7, 2019

Record last verified: 2024-05

Locations

SE (3)