Lidocaine For Neuroprotection During Cardiac Surgery

This study is currently recruiting participants.

Verified June 2013 by Duke University

Sponsor:

Collaborators:

National Institutes of Health (NIH)

CAS Medical Systems, Inc.

Information provided by (Responsible Party):

Duke University

ClinicalTrials.gov Identifier:

NCT00938964

First received: July 10, 2009

Last updated: June 5, 2013

Last verified: June 2013

History of Changes

Purpose

The purpose of this study is to see if a drug called lidocaine prevents cognitive injury (a decline in mental abilities) after heart surgery. Lidocaine is currently FDA approved and is commonly used for treating some heart rhythm disorders and for regional anesthesia (blocking nerves). The investigators are enrolling subjects in this research project to see if lidocaine will reduce the high incidence of cognitive injury seen after heart surgery. As part of this study, the investigators will also evaluate the relationship between cognitive injury and genetic makeup and the chemical changes in the subjects blood during and after surgery.

Condition	Intervention
Cognitive Decline	Drug: Lidocaine Drug: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Lidocaine For Neuroprotection During Cardiac Surgery

Resource links provided by NLM:

MedlinePlus related topics: Heart Surgery

Drug Information available for: Lidocaine hydrochloride Lidocaine

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Change in cognitive function from baseline [ Time Frame: 6 weeks after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Platelet and white blood cell activation gradients [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]

Estimated Enrollment:	476
Study Start Date:	July 2009
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lidocaine Lidocaine infusion for 48 hours	Drug: Lidocaine Lidocaine versus placebo infusion for 48 hours
Placebo Comparator: Placebo Normal saline infusion for 48 hours	Drug: Placebo Lidocaine versus placebo infusion for 48 hours

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

CABG, CABG + Valve, or Valve surgery
Use of cardiopulmonary bypass

Exclusion Criteria:

Less than 50 years of age
History of diabetes
History of symptomatic cerebrovascular disease (e.g. prior stroke) with residual deficit
Alcoholism (> 2 drinks/day)
History of psychiatric illness (any clinical diagnoses requiring therapy)
History of drug abuse (any illicit drug use in the past 3 months)
Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)
Severe pulmonary insufficiency (requiring home oxygen therapy)
Renal failure (baseline serum creatinine > 2.0 mg/dl)
Pregnant women
Unable to read and thus unable to complete the cognitive testing
Score < 24 on a baseline Mini Mental State examination (MMSE) or greater than or equal to 27 on the baseline Center for Epidemiological Studies Depression (CES-D) Scale -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00938964

Contacts

Contact: Joseph P Mathew, M. D.

919-681-6752

mathe014@mc.duke.edu

Locations

United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Joseph P Mathew, M.D. 919-681-9698 mathe014@mc.duke.edu
United States, Virginia
Sentara Cardiovascular Research Institute	Recruiting
Norfolk, Virginia, United States, 23507
Contact: David Schinderle, M. D. 757-620-3609 d-schinderle@cox.net
Principal Investigator: David Schinderle, M. D.

Sponsors and Collaborators

Duke University

National Institutes of Health (NIH)

CAS Medical Systems, Inc.

Investigators

Principal Investigator:

Joseph P Mathew, M. D.

Duke University

More Information

Publications:

Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001 Feb 8;344(6):395-402. Erratum in: N Engl J Med 2001 Jun 14;344(24):1876.

Newman MF, Grocott HP, Mathew JP, White WD, Landolfo K, Reves JG, Laskowitz DT, Mark DB, Blumenthal JA; Neurologic Outcome Research Group and the Cardiothoracic Anesthesia Research Endeavors (CARE) Investigators of the Duke Heart Center. Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery. Stroke. 2001 Dec 1;32(12):2874-81.

Phillips-Bute B, Mathew JP, Blumenthal JA, Grocott HP, Laskowitz DT, Jones RH, Mark DB, Newman MF. Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery. Psychosom Med. 2006 May-Jun;68(3):369-75.

Mathew JP, Mackensen GB, Phillips-Bute B, Grocott HP, Glower DD, Laskowitz DT, Blumenthal JA, Newman MF; Neurologic Outcome Research Group (NORG) of the Duke Heart Center. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009 Mar;40(3):880-7. Epub 2009 Jan 22.

Evans DE, Kobrine AI, LeGrys DC, Bradley ME. Protective effect of lidocaine in acute cerebral ischemia induced by air embolism. J Neurosurg. 1984 Feb;60(2):257-63.

Mitchell SJ. Lidocaine in the treatment of decompression illness: a review of the literature. Undersea Hyperb Med. 2001 Fall;28(3):165-74. Review.

Astrup J, Sørensen PM, Sørensen HR. Inhibition of cerebral oxygen and glucose consumption in the dog by hypothermia, pentobarbital, and lidocaine. Anesthesiology. 1981 Sep;55(3):263-8.

Weber ML, Taylor CP. Damage from oxygen and glucose deprivation in hippocampal slices is prevented by tetrodotoxin, lidocaine and phenytoin without blockade of action potentials. Brain Res. 1994 Nov 21;664(1-2):167-77.

Ayad M, Verity MA, Rubinstein EH. Lidocaine delays cortical ischemic depolarization: relationship to electrophysiologic recovery and neuropathology. J Neurosurg Anesthesiol. 1994 Apr;6(2):98-110.

LoPachin RM, Gaughan CL, Lehning EJ, Weber ML, Taylor CP. Effects of ion channel blockade on the distribution of Na, K, Ca and other elements in oxygen-glucose deprived CA1 hippocampal neurons. Neuroscience. 2001;103(4):971-83.

Zhang Y, Lipton P. Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. J Neurosci. 1999 May 1;19(9):3307-15.

Fujitani T, Adachi N, Miyazaki H, Liu K, Nakamura Y, Kataoka K, Arai T. Lidocaine protects hippocampal neurons against ischemic damage by preventing increase of extracellular excitatory amino acids: a microdialysis study in Mongolian gerbils. Neurosci Lett. 1994 Sep 26;179(1-2):91-4.

Díaz L, Gómez A, Bustos G. Lidocaine reduces the hypoxia-induced release of an excitatory amino acid analog from rat striatal slices in superfusion. Prog Neuropsychopharmacol Biol Psychiatry. 1995 Sep;19(5):943-53.

Dutka AJ, Mink R, McDermott J, Clark JB, Hallenbeck JM. Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism. Stroke. 1992 Oct;23(10):1515-20; discussion 1520-1.

Evans DE, Kobrine AI. Reduction of experimental intracranial hypertension by lidocaine. Neurosurgery. 1987 Apr;20(4):542-7.

Shokunbi MT, Gelb AW, Peerless SJ, Mervart M, Floyd P. An evaluation of the effect of lidocaine in experimental focal cerebral ischemia. Stroke. 1986 Sep-Oct;17(5):962-6.

Sakabe T, Maekawa T, Ishikawa T, Takeshita H. The effects of lidocaine on canine cerebral metabolism and circulation related to the electroencephalogram. Anesthesiology. 1974 May;40(5):433-41. No abstract available.

Johns RA, DiFazio CA, Longnecker DE. Lidocaine constricts or dilates rat arterioles in a dose-dependent manner. Anesthesiology. 1985 Feb;62(2):141-4.

Lei B, Popp S, Capuano-Waters C, Cottrell JE, Kass IS. Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. Neuroscience. 2004;125(3):691-701.

MacGregor RR, Thorner RE, Wright DM. Lidocaine inhibits granulocyte adherence and prevents granulocyte delivery to inflammatory sites. Blood. 1980 Aug;56(2):203-9. No abstract available.

Schmidt W, Schmidt H, Bauer H, Gebhard MM, Martin E. Influence of lidocaine on endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo. Anesthesiology. 1997 Sep;87(3):617-24.

Lan W, Harmon D, Wang JH, Ghori K, Shorten G, Redmond P. The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion. Eur J Anaesthesiol. 2004 Nov;21(11):892-7.

Mitchell SJ, Benson M, Vadlamudi L, Miller P. Cerebral arterial gas embolism by helium: an unusual case successfully treated with hyperbaric oxygen and lidocaine. Ann Emerg Med. 2000 Mar;35(3):300-3.

Mitchell SJ, Pellett O, Gorman DF. Cerebral protection by lidocaine during cardiac operations. Ann Thorac Surg. 1999 Apr;67(4):1117-24.

Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg. 2002 Nov;95(5):1134-41, table of contents.

Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg. 1995 May;59(5):1289-95. No abstract available.

Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills, 1958; 8:271-276

Ruff RM, Parker SB. Gender- and age-specific changes in motor speed and eye-hand coordination in adults: normative values for the Finger Tapping and Grooved Pegboard Tests. Percept Mot Skills. 1993 Jun;76(3 Pt 2):1219-30.

Murkin JM, Stump DA, Blumenthal JA, McKhann G. Defining dysfunction: group means versus incidence analysis--a statement of consensus. Ann Thorac Surg. 1997 Sep;64(3):904-5. Review. No abstract available.

Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine S, Haley EC, Grotta J, Marler J. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke. 1994 Nov;25(11):2220-6.

Roach GW, Newman MF, Murkin JM, Martzke J, Ruskin A, Li J, Guo A, Wisniewski A, Mangano DT. Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Anesthesiology. 1999 May;90(5):1255-64.

Mark DB, Nelson C, Delong E, et al. Comparisin of quality of life outcomes following coronary angioplasty, coronary bypass surgery and medicine. J Am Coll Cardiol. 1993; 21:216A

Cleary PD, Greenfield S, McNeil BJ. Assessing quality of life after surgery. Control Clin Trials. 1991 Aug;12(4 Suppl):189S-203S.

Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol. 1989 Sep 15;64(10):651-4.

Ware JE Jr. Standards for validating health measures: definition and content. J Chronic Dis. 1987;40(6):473-80. Review.

Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, Berman LB. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J. 1985 Apr 15;132(8):919-23.

Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation. 1981 Dec;64(6):1227-34.

McDowell I, Newell C. Measuring Health: A Guide To Rating Scales And Questionnaires. New York: Oxford University Press; 1987.

Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981 Aug;19(8):787-805.

Wassertheil-Smoller S, Blaufox MD, Oberman A, Davis BR, Swencionis C, Knerr MO, Hawkins CM, Langford HG. Effect of antihypertensives on sexual function and quality of life: the TAIM Study. Ann Intern Med. 1991 Apr 15;114(8):613-20.

Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Statist Soc B. 1995;57(1):289-300

Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT00938964 History of Changes
Other Study ID Numbers:	Pro00015641, R01HL096978
Study First Received:	July 10, 2009
Last Updated:	June 5, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

Cognition

Additional relevant MeSH terms:

Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Lidocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs

Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on June 17, 2013

To Top