Lidocaine For Neuroprotection During Cardiac Surgery

Cognitive Decline Clinical Trial

Official title:

Lidocaine For Neuroprotection During Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00938964
• Other study ID #: Pro00015641
• Secondary ID: R01HL096978
• Status: Completed
• Phase: N/A
• Start date: July 2009
• Est. completion date: May 23, 2017

Study information

• Verified date: May 2019
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 550
• Est. completion date: May 23, 2017
• Est. primary completion date: July 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction

Intervention

Drug:
• Lidocaine
Lidocaine versus placebo infusion for 48 hours
• Placebo
Lidocaine versus placebo infusion for 48 hours

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	CAS Medical Systems, Inc., National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (45)

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* Note: There are 45 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cognitive Function From Baseline Characterized as Continuous Cognitive Change	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 standard deviation of 0.35. A negative change score indicating decline and a positive score indicating improvement.	Preoperative to 6 weeks after surgery
Primary	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	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.	Preoperative to 6 weeks after surgery
Secondary	Transcerebral Activation Gradients of Platelets	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	Baseline to 6 hours post cross-clamp removal
Secondary	Transcerebral Activation Gradients of Neutrophils	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	Baseline to 6 hours post cross-clamp removal
Secondary	Transcerebral Activation Gradients of Monocytes	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	Baseline to 6 hours post cross-clamp removal
Secondary	Transcerebral Activation Gradient of Platelet-neutrophil Conjugates	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	Baseline to 6 hours post cross-clamp removal
Secondary	Change in Cognitive Function From Baseline	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 1 year cognitive index. The resulting outcome measure is unbounded with standard deviation of 0.35. A negative change score indicating decline and a positive score indicating improvement	1 year after surgery
Secondary	Change in Duke Activity Status Index (DASI)	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.	baseline, 6-weeks
Secondary	Change in Duke Activity Status Index (DASI)	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.	baseline, 1-year
Secondary	Change in Neurological Function, as Measured by the National Institutes of Health Stroke Scale (NIHSS)	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).	baseline, 6-weeks
Secondary	Change in Neurological Function, as Measured by the National Institutes of Health Stroke Scale (NIHSS)	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).	baseline, 1-year
Secondary	Change in Center for Epidemiological Studies Depression Scale (CES-D)	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.	baseline, 6-weeks
Secondary	Change in Center for Epidemiological Studies Depression Scale (CES-D)	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.	baseline, 1-year
Secondary	Change in Spielberger State Anxiety Inventory (STAI)	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.	baseline, 6-weeks
Secondary	Change in Spielberger State Anxiety Inventory (STAI)	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.	baseline, 1-year
Secondary	Change in Symptom Limitations	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.	baseline, 6-weeks
Secondary	Change in Symptom Limitations	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.	baseline, 1-year
Secondary	Change in the Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL)	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.	baseline, 6-weeks
Secondary	Change in the Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL)	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.	baseline, 1-year
Secondary	Change in the Cognitive Difficulties Scale	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.	baseline, 6-weeks
Secondary	Change in the Cognitive Difficulties Scale	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.	baseline, 1-year
Secondary	Change in Perceived Social Support	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.	baseline, 6-weeks
Secondary	Change in Perceived Social Support	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.	baseline, 1-year
Secondary	Change in Social Activity	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.	baseline, 6-weeks
Secondary	Change in Social Activity	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.	baseline, 1-year
Secondary	Change in Study 36-Item Short Form Health Survey (SF-36)	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.	baseline, 6-weeks
Secondary	Change in Study 36-Item Short Form Health Survey (SF-36)	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.	baseline, 1-year
Secondary	Change in Neurological Function, as Measured by the Western Perioperative Neurologic Scale (WPNS)	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.	baseline, 6-weeks
Secondary	Change in Neurological Function, as Measured by the Western Perioperative Neurologic Scale (WPNS)	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.	baseline, 1-year