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Lidocaine For Neuroprotection During Cardiac Surgery

This study has been completed.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
CAS Medical Systems, Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00938964
First received: July 10, 2009
Last updated: August 23, 2017
Last verified: July 2017
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Lidocaine For Neuroprotection During Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in Cognitive Function From Baseline Characterized as Continuous Cognitive Change [ Time Frame: Preoperative to 6 weeks after surgery ]
    To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 14 cognitive test scores from baseline. We chose a five-factor solution, which represents 5 cognitive domains: structured verbal memory, unstructured verbal memory, executive function, visual memory and attention/concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 5 preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. The resulting outcome measure is unbounded with a negative score indicating decline and a positive score indicating improvement.

  • Count of Participants With a Decline of Greater Than or Equal to One Standard Deviation in One or More of Five Cognitive Domain Scores Reported as a Dichotomous Post-operative Cognitive Deficit (POCD) Outcome [ Time Frame: Preoperative to 6 weeks after surgery ]
    To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 14 cognitive test scores from baseline. We chose a five-factor solution, which represents 5 cognitive domains: structured verbal memory, unstructured verbal memory, executive function, visual memory and attention/concentration. Each domain score is normally distributed with a mean of zero. A change score was calculated for each domain by subtracting the baseline from the 6-week score. A dichotomous outcome variable of post-operative cognitive deficit was defined as a decline of ≥1 standard deviation in 1 or more of the 5 domains.


Secondary Outcome Measures:
  • Transcerebral Activation Gradients of Platelets [ Time Frame: Baseline to 6 hours post cross-clamp removal ]
    Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

  • Transcerebral Activation Gradients of Neutrophils [ Time Frame: Baseline to 6 hours post cross-clamp removal ]
    Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removal and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

  • Transcerebral Activation Gradients of Monocytes [ Time Frame: Baseline to 6 hours post cross-clamp removal ]
    Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

  • Transcerebral Activation Gradient of Platelet-neutrophil Conjugates [ Time Frame: Baseline to 6 hours post cross-clamp removal ]
    Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

  • Change in Cognitive Function From Baseline [ Time Frame: 1 year after surgery ]
  • Change in Duke Activity Status Index (DASI) [ Time Frame: baseline, 6-weeks ]
    The DASI is a 12-item scale of functional capacity that has been found to correlate well with objective measures of maximal exercise capacity. Items reflect activities of personal care, ambulation, household tasks, sexual function, and recreational activities. Activities done "with no difficulty" receive scores, which are weighted and summed, for a quantitative measure of functional status. Scores range from 0 to 60; a higher-weighted score indicates better function.

  • Change in Duke Activity Status Index (DASI) [ Time Frame: baseline, 1-year ]
    The DASI is a 12-item scale of functional capacity that has been found to correlate well with objective measures of maximal exercise capacity. Items reflect activities of personal care, ambulation, household tasks, sexual function, and recreational activities. Activities done "with no difficulty" receive scores, which are weighted and summed, for a quantitative measure of functional status. Scores range from 0 to 60; a higher-weighted score indicates better function.

  • Change in Neurological Function, as Measured by the National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: baseline, 6-weeks ]
    The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).

  • Change in Neurological Function, as Measured by the National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: baseline, 1-year ]
    The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).

  • Change in Center for Epidemiological Studies Depression Scale (CES-D) [ Time Frame: baseline, 6-weeks ]
    Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report examination designed to measure symptoms of depression. Subjects rate the degree to which they have experienced a range of symptoms of depression, such as "I had crying spells" and "I felt lonely." Scores range from 0 to 60, with higher scores indicating greater depressive symptoms. Scores greater than 16 are typically considered indicative of clinically significant depression.

  • Change in Center for Epidemiological Studies Depression Scale (CES-D) [ Time Frame: baseline, 1-year ]
    Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report examination designed to measure symptoms of depression. Subjects rate the degree to which they have experienced a range of symptoms of depression, such as "I had crying spells" and "I felt lonely." Scores range from 0 to 60, with higher scores indicating greater depressive symptoms. Scores greater than 16 are typically considered indicative of clinically significant depression.

  • Change in Spielberger State Anxiety Inventory (STAI) [ Time Frame: baseline, 6-weeks ]
    Spielberger State Anxiety Inventory (STAI): The STAI consists of two 20-item scales that measure anxiety. Representative items include statements such as "I feel nervous" and "I feel worried." These items are rated on a 4-point scale, based on how well they describe the patient's current or typical mood, from "not at all" to "very much so." Scores range from 20 to 80, with higher scores indicating greater anxiety.

  • Change in Spielberger State Anxiety Inventory (STAI) [ Time Frame: baseline, 1-year ]
    Spielberger State Anxiety Inventory (STAI): The STAI consists of two 20-item scales that measure anxiety. Representative items include statements such as "I feel nervous" and "I feel worried." These items are rated on a 4-point scale, based on how well they describe the patient's current or typical mood, from "not at all" to "very much so." Scores range from 20 to 80, with higher scores indicating greater anxiety.

  • Change in Symptom Limitations [ Time Frame: baseline, 6-weeks ]
    Symptom limitations: Patients were given a list of eight symptoms and asked to rate the degree to which the symptom limited daily activities. The symptoms were angina, shortness of breath, arthritis, back trouble, leg pains, headaches, fatigue, and other. Scores range from 8 to 32, with higher scores indicating greater limitations.

  • Change in Symptom Limitations [ Time Frame: baseline, 1-year ]
    Symptom limitations: Patients were given a list of eight symptoms and asked to rate the degree to which the symptom limited daily activities. The symptoms were angina, shortness of breath, arthritis, back trouble, leg pains, headaches, fatigue, and other. Scores range from 8 to 32, with higher scores indicating greater limitations.

  • Change in the Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL) [ Time Frame: baseline, 6-weeks ]
    Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL): This measure contains six items that assess the ability to perform important tasks for daily living (e.g., "Could you prepare your own meals?" "Could you drive a car?"). Scores range from 6 to 24. Higher scores indicate increasing difficulty in engaging in daily activities.

  • Change in the Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL) [ Time Frame: baseline, 1-year ]
    Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL): This measure contains six items that assess the ability to perform important tasks for daily living (e.g., "Could you prepare your own meals?" "Could you drive a car?"). Scores range from 6 to 24. Higher scores indicate increasing difficulty in engaging in daily activities.

  • Change in the Cognitive Difficulties Scale [ Time Frame: baseline, 6-weeks ]
    Cognitive Difficulties Scale: a 39-item scale, is a self-report assessment of perceived problems in long- and short-term memory, concentration, attention, and psycho-motor coordination. Sample items are "I forget errands I planned to do" and "I fail to recognize people I know." Scores range from 39 to 164, with higher scores indicating greater cognitive difficulty.

  • Change in the Cognitive Difficulties Scale [ Time Frame: baseline, 1-year ]
    Cognitive Difficulties Scale: a 39-item scale, is a self-report assessment of perceived problems in long- and short-term memory, concentration, attention, and psycho-motor coordination. Sample items are "I forget errands I planned to do" and "I fail to recognize people I know." Scores range from 39 to 164, with higher scores indicating greater cognitive difficulty.

  • Change in Perceived Social Support [ Time Frame: baseline, 6-weeks ]
    Perceived Social Support Scale: Twelve items indicate how strongly subjects agree that there is "a special person who is around when I am in need" and "my family really tries to help me." Choices range from "very strongly disagree" to "very strongly agree." Items are summed for a range of 12 to 84, with a high score meaning more social support.

  • Change in Perceived Social Support [ Time Frame: baseline, 1-year ]
    Perceived Social Support Scale: Twelve items indicate how strongly subjects agree that there is "a special person who is around when I am in need" and "my family really tries to help me." Choices range from "very strongly disagree" to "very strongly agree." Items are summed for a range of 12 to 84, with a high score meaning more social support.

  • Change in Social Activity [ Time Frame: baseline, 6-weeks ]
    Social Activity: This measure consisted of eight items that indicate the degree of social interaction. Sample items are "How often do you talk on the telephone with friends and relatives?" and "How often do you attend meetings of social groups, clubs, or civic organizations?" Scores range from 8 to 32. A lower score indicates more social activity.

  • Change in Social Activity [ Time Frame: baseline, 1-year ]
    Social Activity: This measure consisted of eight items that indicate the degree of social interaction. Sample items are "How often do you talk on the telephone with friends and relatives?" and "How often do you attend meetings of social groups, clubs, or civic organizations?" Scores range from 8 to 32. A lower score indicates more social activity.

  • Change in Study 36-Item Short Form Health Survey (SF-36) [ Time Frame: baseline, 6-weeks ]
    The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36): The SF-36 was designed to measure general health status. Two scales were used: Work Activities (four items) and General Health (one item). For the work activities scale, the reported score was the sum of four questions, each with values ranging from 1 to 4, the total score could range from 4 to 16. A higher score on Work Activities indicates more health-related problems For the general health question, the patients ranked their health from Excellent (1) to poor (5), the scale ranged from 1 to 5 with 1 being best health and 5 being worst. A high score in General Health indicates poorer health state.

  • Change in Study 36-Item Short Form Health Survey (SF-36) [ Time Frame: baseline, 1-year ]
    The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36): The SF-36 was designed to measure general health status. Two scales were used: Work Activities (four items) and General Health (one item). For the work activities scale, the reported score was the sum of four questions, each with values ranging from 1 to 4, the total score could range from 4 to 16. A higher score on Work Activities indicates more health-related problems For the general health question, the patients ranked their health from Excellent (1) to poor (5), the scale ranged from 1 to 5 with 1 being best health and 5 being worst. A high score in General Health indicates poorer health state.

  • Change in Neurological Function, as Measured by the Western Perioperative Neurologic Scale (WPNS) [ Time Frame: baseline, 6-weeks ]
    The Western perioperative neurologic scale was designed to detect neurologic deficits after cardiac surgery. It includes 14 items classified into eight domains (mentation, speech, cranial nerve function, motor weakness, sensation and cerebellum, reflexes, and gait). Each item is scored from 0 (severe deficit) to3 (normal), and a maximum score of 42 indicates normal neurological function.

  • Change in Neurological Function, as Measured by the Western Perioperative Neurologic Scale (WPNS) [ Time Frame: baseline, 1-year ]
    The Western perioperative neurologic scale was designed to detect neurologic deficits after cardiac surgery. It includes 14 items classified into eight domains (mentation, speech, cranial nerve function, motor weakness, sensation and cerebellum, reflexes, and gait). Each item is scored from 0 (severe deficit) to3 (normal), and a maximum score of 42 indicates normal neurological function.


Enrollment: 550
Actual Study Start Date: July 2009
Study Completion Date: May 23, 2017
Primary Completion Date: July 18, 2016 (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   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CABG, CABG + Valve, or Valve surgery
  2. Use of cardiopulmonary bypass

Exclusion Criteria:

  1. Less than 50 years of age
  2. History of diabetes
  3. History of symptomatic cerebrovascular disease (e.g. prior stroke) with residual deficit
  4. Alcoholism (> 2 drinks/day)
  5. History of psychiatric illness (any clinical diagnoses requiring therapy)
  6. History of drug abuse (any illicit drug use in the past 3 months)
  7. Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)
  8. Severe pulmonary insufficiency (requiring home oxygen therapy)
  9. Renal failure (baseline serum creatinine > 2.0 mg/dl)
  10. Pregnant women
  11. Unable to read and thus unable to complete the cognitive testing
  12. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Virginia
Sentara Cardiovascular Research Institute
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
CAS Medical Systems, Inc.
Investigators
Principal Investigator: Joseph P Mathew, M. D. Duke University
  More Information

Publications:
Rey A. L'examen clinique en psychologie. Paper presented at : Presses Universitaires de France, 1964; Paris
Randt C, Brown E. Administration Manual: Randt Memory Test. New Youk Life Sciences Associates; 1983
Wechsler D. The Wechsler Adult Intelligence Sacle-Revised (Manual): Psychological Corporation: 1981.
Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills, 1958; 8:271-276
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
McDowell I, Newell C. Measuring Health: A Guide To Rating Scales And Questionnaires. New York: Oxford University Press; 1987.
Cronbach LJ. Essentials of Psycological Testing. New York: Harper and Row; 1970
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00938964     History of Changes
Other Study ID Numbers: Pro00015641
R01HL096978 ( U.S. NIH Grant/Contract )
Study First Received: July 10, 2009
Results First Received: July 18, 2017
Last Updated: August 23, 2017

Keywords provided by Duke University:
Cognition

Additional relevant MeSH terms:
Lidocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017