Cerebral Monitor Guided Therapy on Cerebral Outcomes After Cardiac Surgery

February 19, 2021 updated by: Kei Togashi, University of Washington

Randomized, Prospective Clinical Study Aiming to Assess the Impact of Cerebral Monitoring Guided Therapy on Cerebral Outcomes After Cardiac Surgery

The purpose of this study is to compare patients' metabolomic profiles who are managed with a brain monitor that measures cerebral oxygen to those who are managed by conventional measures to hopefully decrease postoperative neurologic and cognitive deficits and improve quality of life.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Neurologic and cognitive decline remain common complications that adversely affect patients' outcome after cardiac surgery. By incorporating a brain monitor that measures cerebral oxygen content into our perioperative management we aim to decrease postoperative neurologic and cognitive deficits and improve quality of life in this patient population. We also aim to uncover how the compromised brain alters its metabolism in response to ischemic injury and how this new information can guide new preventive treatment methods for vulnerable patients.

Briefly, cerebral near-infrared spectroscopy (NIRS) or cerebral oximetry is a non-invasive monitor that estimates cerebral oxygenation through measurements of regional venous saturation. It is based on measuring intravascular oxyhemoglobin fraction in a small sample of cerebral cortex through the skull using near-infrared light spectroscopy. Cerebral oximetry examines all reflected light, from both pulsatile arterial and non-pulsatile venous blood, without requiring pulsatility, hence cerebral oximetry can continue to monitor brain oxygenation during both CPB and circulatory arrest. With this advantage, cerebral oximetry is widely utilized in our daily cardiac anesthesia practice, routinely for surgeries requiring circulatory arrest, and for other elective CABG and valve replacement/repair surgeries in some institutions. Despite its wide use, controversy still exists in its interpretation and ability to optimize cerebral outcome after cardiac surgery. Key questions to be answered are: 1) the desaturation threshold associated with poor prognosis; 2) the absolute desaturation value at which adverse clinical outcome increases, and 3); if the relative trend is more important to signal approaching deterioration. All of these questions are relevant to our clinical practice yet remain unanswered. Our research study aims to take a first step towards identification of the ideal method of utilizing cerebral oximetry in cardiac surgeries to improve neurological outcome through increasing precision in managing hemodynamic as well as laboratory values through a treatment algorithm.

The second component of this study incorporates metabolomic profiling as we refine the perioperative management of cardiac surgery patient to improve their cerebral outcome. Despite enormous research efforts over the last decades, currently there is no specific and single neurologic biomarker (or panels of biomarkers) that has been validated for clinical use. Meanwhile, neuro-imaging (CT and MRI) remains the gold standard for the diagnosis of cerebral injury. Organ-specific biomarkers, if identified, have the potential to be a reliable and cost-effective method to diagnose, guide management, classify severity of stroke, anticipate cognitive function, and predict complications. Recently, metabolomic profiling has enabled comprehensive analyses of changes in metabolic fuel selection in a variety of models, including cardioplegic arrest. Advances in analytical technology have enabled quantitative analysis of several hundreds of metabolites in a single measurement with high throughput and sensitivity.

Metabolomic profiling entails quantitating small-molecule metabolites from body fluids or tissues in a single step, and possesses the potential for early diagnosis, therapy monitoring and investigating the pathogenesis of various diseases. This biomarker detection is conducted in cells, tissues, or biofluids by either nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS) which then undergoes multivariate data analysis. Jung et al., using 1H-NMR spectropy combined with multivariate statistical analysis assessed stroke patients. In this study perturbed metabolic pattern in both plasma and urine from patients with known cerebral infarction incidents were assessed to identify a specific proteome associated with stroke. A similar investigation has been conducted with a wider quantification of neuroproteomics using a rodent model. Biomarker prognostic of acute kidney injury in patients undergoing cardiopulmonary bypass (CPB) has also been investigated. Despite its potential for wide application, metabolomic profiling has not seen its utilization to guide neuroprotective management in patients undergoing cardiac surgery. We believe the unique combination of these two methods poses a valuable opportunity not only to improve the patient's neurocognitive outcome, but also to gain insights on which biomarkers represent cerebral ischemia or other signs of cerebral injury.

Our specific aims are to: 1. Assess the transcerebral metabolomic profile and neurocognitive outcome in response to cerebral injury in patients monitored and treated according to cerebral oximetry (NIRS) and those that are just monitored with NIRS.

Based on available literature, our working hypothesis is that compared to monitored only patients, cerebral fuel utilization will be differentially affected in patients monitored and treated by tightly following a specific neuroprotective algorithm.

1.a. Test the plasma concentrations of metabolites representing the amino acid, carbohydrate, energy, lipid, and nucleotide pathways using nuclear magnetic resonance (NMR) and mass spectrometry.

1.b. Compare the neurocognitive function of treated and untreated patients using a comprehensive test battery consisting of 5 assessment modalities at baseline, at the time of discharge and 6 weeks postoperatively.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Kei Togashi, MD MPH
  • Phone Number: 2065981994
  • Email: ktogashi@uw.edu

Study Contact Backup

  • Name: G. Burkhard Mackensen, MD PhD FASE
  • Phone Number: 2065981462
  • Email: gbmac@uw.edu

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
        • Contact:
          • G. Burkhard Mackensen, MD PhD FASE
          • Phone Number: 2065981462
          • Email: gbmac@uw.edu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult cardiac surgery patients undergoing cardio-pulmonary bypass (CPB) with cardioplegic arrest (CABG, valves, CABG + valves).

Exclusion Criteria:

  • History of a stroke within 90 days prior to enrollment, or a history of cerebral vascular disease with significant (> 80%) extra cranial stenosis;
  • Technical obstacles, which pose an inordinately high surgical risk, in the judgment of the investigator;
  • Existence of any ongoing mechanical circulatory support other than intra- aortic balloon counter pulsation;
  • Body Mass Index (BMI) > 50 kg/m2;
  • Pregnancy;
  • Psychiatric disease, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol;
  • Presence of active, uncontrolled infection;
  • Evidence of intrinsic hepatic disease as defined by liver enzyme values;
  • Participation in any other clinical investigation that is likely to confound study results or affect study outcome;
  • Patient refuses to be enrolled in study;
  • Institution inmates

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intervention Group
  • Maintain rSO2 values at or above 75% of the baseline
  • Midline position
  • Target CO2 of ≥40 mmHg, target MAP >60 mm Hg
  • Maintain cerebral perfusion pressure >50 mm Hg
  • Target pump flow 2.5 L/m2/min

  • If rSO2 persistently below treatment threshold:

    • FiO2 is increased
    • or propofol 50-100 mg bolus is administered
  • If Hct below 20% packed red blood cells will be transfused

timeline: before induction, after time-out has been performed, and will continue until 24 hours post surgery.
Other: Perioperative and postoperative management
Cerebral oximetry informed perioperative management
No Intervention: Control Group
Patients in the control group will be managed under the attending physician's discretion. Cerebral oximetry data will be collected in the same fashion as in the intervention group, but the measurements will be blinded to the physician. Blood samples will be collected for metabolomic profiling in the same fashion and at identical time points as the intervention group for later analysis.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assessing Change in Metabolomic Profile via Mass Spectrometry and NMR
Time Frame: Blood samples taken1) At baseline following placement, 2) 30 min after initiation of bypass; 3) 10 min before separation from bypass; 4) 2 hours after separation from bypass and 5) before removal of the catheter or 12 hours after the end of surgery
Blood samples will be tested for potential organ-specific biomarker to diagnose and classify cerebral protein consumption to assess neurological activity.
Blood samples taken1) At baseline following placement, 2) 30 min after initiation of bypass; 3) 10 min before separation from bypass; 4) 2 hours after separation from bypass and 5) before removal of the catheter or 12 hours after the end of surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Neurocognitive
Time Frame: baseline, 6 weeks post-operation
Neurocognitive test battery
baseline, 6 weeks post-operation
Neurologic via CAM ICU and RASS Score During the Acute Post-Operative ICU Stay
Time Frame: To be gathered as a part of routine critical care assessment throughout the participant's ICU stay. Up to 2 weeks post surgery
Neurologic clinical testing
To be gathered as a part of routine critical care assessment throughout the participant's ICU stay. Up to 2 weeks post surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Washington

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kei Togashi, MD MPH, University of Washington

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 20, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00002376

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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