Lidocaine For Neuroprotection During Cardiac Surgery

NCT00938964 | Completed Results DMC

• 2 other identifiers: Pro00015641R01HL096978
• Study Type: interventional
• Target: 550
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Cognitive Decline

Keywords

Cognition

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (27)

• Transcerebral Activation Gradients of Platelets

  Baseline to 6 hours post cross-clamp removal

• Transcerebral Activation Gradients of Neutrophils

  Baseline to 6 hours post cross-clamp removal

• Transcerebral Activation Gradients of Monocytes

  Baseline to 6 hours post cross-clamp removal

• Transcerebral Activation Gradient of Platelet-neutrophil Conjugates

  Baseline to 6 hours post cross-clamp removal

• Change in Cognitive Function From Baseline

  1 year after surgery

Study Arms (2)

Lidocaine

EXPERIMENTAL

Lidocaine infusion for 48 hours

Drug: Lidocaine

Placebo

PLACEBO COMPARATOR

Normal saline infusion for 48 hours

Drug: Placebo

Interventions

Lidocaine DRUG

Lidocaine versus placebo infusion for 48 hours

Lidocaine

Placebo DRUG

Lidocaine versus placebo infusion for 48 hours

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 -

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• CAS Medical Systems, Inc.: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

Related Publications (46)

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MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Lidocaine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Joseph Mathew, M.D
• Organization: Duke University Health System

joseph.mathew@duke.edu

919-681-6646

Study Officials

• Joseph P Mathew, M. D.

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2009
• First Posted: July 14, 2009
• Study Start: July 1, 2009
• Primary Completion: July 18, 2016
• Study Completion: May 23, 2017
• Last Updated: May 10, 2019
• Results First Posted: August 24, 2017

Record last verified: 2019-05

Locations

US (2)