Back to resultsThe PATHFINDER Study: A Feasibility Trial (PATHFINDER)
Primary Purpose
Coronary Artery Disease, Delirium
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ropivacaine
Ketamine
Remifentanil
Dexmedetomidine
Rocuronium
Propofol
Sevoflurane
Dexmedetomidine
Propofol
EEG monitoring
Sponsored by
About this trial
This is an interventional other trial for Coronary Artery Disease focused on measuring Cardiopulmonary Bypass, Cardiac Surgery, analgesics
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 60 years
- Undergoing any of the following types of surgery with cardiopulmonary bypass limited to coronary artery bypass surgery (CABG), CABG+valve surgeries and isolated valve surgeries.
Exclusion Criteria:
- Preoperative left ventricular ejection fraction (LVEF) <30%
- Emergent surgery
- Non-English speaking
- Cognitive impairment as defined by total MoCA score < 10
- Currently enrolled in another interventional study that could impact the primary outcome, as determined by the PI
- Significant visual impairment
- Chronic opioid use for chronic pain conditions with tolerance (total dose of an opioid at or more than 30 mg morphine equivalent for more than one month within the past year)
- Hypersensitivity to any of the study medications
- Known history of alcohol (> 2 drinks per day) or drug abuse Active (in the past year) history of alcohol abuse (≥5 drinks/day for men or ≥4 drinks/day for women) as determined by reviewing medical record and history given by the patient
- Liver dysfunction (liver enzymes > 4 times the baseline, all patients will have a baseline liver function test evaluation), history and examination suggestive of jaundice.
Sites / Locations
- Beth Israel Deaconess Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Multimodal General Anesthesia
Standard Practice with EEG monitoring
Arm Description
Intraoperative The anesthesiologists involved in this study will be trained to infer differences in anti-nociception, unconsciousness movement and changes during other perioperative events by monitoring EEG. They will also be trained in titrating hypnotic and nociceptic medications based on changes in EEG. Routine anesthetic induction Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.25% ropivacaine on either side of the sternum after anesthetic induction but before surgical incision Ketamine (0.06 to 0.12 mg.kg/hr) Remifentanil (0.05-0.2 mcg/kg/min) Dexmedetomidine (0.2-1.0 mcg/kg/hr) Rocuronium intermittent bolus (TOF) Propofol infusion ± Sevoflurane titrated based on EEG monitoring Postoperative Standard pain management protocol Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided) Infusion continued till extubation Propofol infusion may be added/used for sedation based on the treating physician's discretion
The initial 2 patients will receive standard anesthesia practice and perioperative EEG monitoring will be recorded to learn the patterns associated with our standard practice.
Outcomes
Primary Outcome Measures
Incidence of Delirium
Incidence of delirium will be analyzed in patients treated with the multi-modal approach. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM)Assessment Method (CAM) algorithm postoperatively until discharge.
Secondary Outcome Measures
Time to extubation
Time to extubation will be noted from ICU data
Montreal Cognitive Assessment (MoCA)
MoCA scores (total possible score is 30 points; a score of 26 or above is considered normal) at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Study staff trained in administering the assessments will collect the data.
Pain scores
Patient reported pain scores on a scale from 0-10 (0 no pain,10 extreme pain), until discharge for the index admission.
Total opioid and supplemental analgesic consumption
The total opioid dosage and supplemental analgesic dosage received in the first 48 hours postoperatively will be abstracted from the medical record.
ICU
Total duration of stay in ICU for the index admission
ICU/hospital length of stay
Their stay in the hospital for the index admission
In-hospital complications
stroke, myocardial infarction (MI), acute kidney injury, pneumonia, reintubation, congestive heart failure, sepsis, reopening of sternum and all-cause mortality
Follow up incidence of delirium
The follow up incidence of delirium will be analyzed at 1 month and 6 months after discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the MoCA/t-MoCA.
Full Information
NCT ID
NCT04016740
First Posted
July 9, 2019
Last Updated
January 27, 2021
Sponsor
Beth Israel Deaconess Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04016740
Brief Title
The PATHFINDER Study: A Feasibility Trial
Acronym
PATHFINDER
Official Title
Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
August 20, 2019 (Actual)
Primary Completion Date
February 19, 2020 (Actual)
Study Completion Date
July 7, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive dysfunction up to 6 months following cardiac surgery.
Detailed Description
The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive dysfunction up to 6 months following cardiac surgery.
Specific Aim 1: The feasibility of implementing multimodal general anesthesia strategy in the Operating Rooms (OR) Specific Aim 2: The feasibility of implementing EEG guided sedation until extubation in the Intensive Care Unit (ICU) Specific Aim 3: The enhancement of recovery after surgery (shorter ventilation time, ICU stay, hospital length of stay) Specific Aim 4: To estimate the effect size of decrease in postoperative day (POD) and postoperative cognitive dysfunction (POCD) to power future large randomized trials
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Delirium
Keywords
Cardiopulmonary Bypass, Cardiac Surgery, analgesics
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
2 roll-in patients followed by 20 patients in the interventional model.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Multimodal General Anesthesia
Arm Type
Experimental
Arm Description
Intraoperative
The anesthesiologists involved in this study will be trained to infer differences in anti-nociception, unconsciousness movement and changes during other perioperative events by monitoring EEG. They will also be trained in titrating hypnotic and nociceptic medications based on changes in EEG.
Routine anesthetic induction
Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.25% ropivacaine on either side of the sternum after anesthetic induction but before surgical incision
Ketamine (0.06 to 0.12 mg.kg/hr)
Remifentanil (0.05-0.2 mcg/kg/min)
Dexmedetomidine (0.2-1.0 mcg/kg/hr)
Rocuronium intermittent bolus (TOF)
Propofol infusion ± Sevoflurane titrated based on EEG monitoring
Postoperative
Standard pain management protocol
Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided)
Infusion continued till extubation
Propofol infusion may be added/used for sedation based on the treating physician's discretion
Arm Title
Standard Practice with EEG monitoring
Arm Type
Other
Arm Description
The initial 2 patients will receive standard anesthesia practice and perioperative EEG monitoring will be recorded to learn the patterns associated with our standard practice.
Intervention Type
Drug
Intervention Name(s)
Ropivacaine
Intervention Description
Intraoperative bilateral PIFB block with 20 mL of 0.25% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Remifentanil
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Rocuronium
Intervention Description
Intraoperative intermittent bolus
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Intraoperative infusion
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Intervention Description
Intraoperative inhaled as needed
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Post-operative infusion
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Post-operative infusion
Intervention Type
Device
Intervention Name(s)
EEG monitoring
Intervention Description
Perioperative monitoring
Primary Outcome Measure Information:
Title
Incidence of Delirium
Description
Incidence of delirium will be analyzed in patients treated with the multi-modal approach. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM)Assessment Method (CAM) algorithm postoperatively until discharge.
Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Secondary Outcome Measure Information:
Title
Time to extubation
Description
Time to extubation will be noted from ICU data
Time Frame
Time of ICU admission until time of extubation in ICU, an average of 6 hours
Title
Montreal Cognitive Assessment (MoCA)
Description
MoCA scores (total possible score is 30 points; a score of 26 or above is considered normal) at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Study staff trained in administering the assessments will collect the data.
Time Frame
On the day of discharge, an average of 6 days
Title
Pain scores
Description
Patient reported pain scores on a scale from 0-10 (0 no pain,10 extreme pain), until discharge for the index admission.
Time Frame
At 4-8 hourly intervals every day until discharge, an average of 6 days
Title
Total opioid and supplemental analgesic consumption
Description
The total opioid dosage and supplemental analgesic dosage received in the first 48 hours postoperatively will be abstracted from the medical record.
Time Frame
48 hours, post-operative
Title
ICU
Description
Total duration of stay in ICU for the index admission
Time Frame
Time of ICU admission until time of discharge to hospital floor; through the hospital stay, an average of 5 days
Title
ICU/hospital length of stay
Description
Their stay in the hospital for the index admission
Time Frame
Time of stay in the hospital until discharge to floor or rehab, an average of 5 days
Title
In-hospital complications
Description
stroke, myocardial infarction (MI), acute kidney injury, pneumonia, reintubation, congestive heart failure, sepsis, reopening of sternum and all-cause mortality
Time Frame
7 days post-op on an average
Title
Follow up incidence of delirium
Description
The follow up incidence of delirium will be analyzed at 1 month and 6 months after discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the MoCA/t-MoCA.
Time Frame
Patients will be assessed for delirium at 1 month and 6 months following the date of surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 60 years
Undergoing any of the following types of surgery with cardiopulmonary bypass limited to coronary artery bypass surgery (CABG), CABG+valve surgeries and isolated valve surgeries.
Exclusion Criteria:
Preoperative left ventricular ejection fraction (LVEF) <30%
Emergent surgery
Non-English speaking
Cognitive impairment as defined by total MoCA score < 10
Currently enrolled in another interventional study that could impact the primary outcome, as determined by the PI
Significant visual impairment
Chronic opioid use for chronic pain conditions with tolerance (total dose of an opioid at or more than 30 mg morphine equivalent for more than one month within the past year)
Hypersensitivity to any of the study medications
Known history of alcohol (> 2 drinks per day) or drug abuse Active (in the past year) history of alcohol abuse (≥5 drinks/day for men or ≥4 drinks/day for women) as determined by reviewing medical record and history given by the patient
Liver dysfunction (liver enzymes > 4 times the baseline, all patients will have a baseline liver function test evaluation), history and examination suggestive of jaundice.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Balachundhar Subramaniam, MD, MPH
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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The PATHFINDER Study: A Feasibility Trial
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