Brief Summary
Our objective is to find an effective prophylactic intervention by evaluating IV acetaminophen's impact in reducing the frequency of postoperative delirium, one of the most common and detrimental complications of cardiac surgery in older adults.
Brief Title
PANDORA: Delirium Prevention After Cardiac Surgery Using IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
Detailed Description
This project will study the impact of scheduled administration of IV acetaminophen on the incidence, duration, and severity of postoperative delirium and other important hospital outcomes. Additionally, this trial will evaluate the effects of IV acetaminophen on longer-term postoperative cognitive dysfunction and functional status and develop a biorepository of perioperative samples as a future resource to probe the mechanisms of postoperative delirium.
The investigators propose three specific aims by conducting a randomized, triple-blind clinical trial that enrolls 900 patients 60 years of age or older undergoing cardiac surgery. Through this trial, the investigators will determine the effect of IV acetaminophen on;
1. the incidence, duration, and severity of postoperative delirium,
2. the use of opioids and other rescue analgesics in the first 48 postoperative hours, daily pain scores at rest and exertion, and length of stay in the Intensive Care Unit and overall hospital length of stay
3. longer-term (one, six, 12 months) cognitive, physical, and self-care functional recovery after surgery.
The investigators propose three specific aims by conducting a randomized, triple-blind clinical trial that enrolls 900 patients 60 years of age or older undergoing cardiac surgery. Through this trial, the investigators will determine the effect of IV acetaminophen on;
1. the incidence, duration, and severity of postoperative delirium,
2. the use of opioids and other rescue analgesics in the first 48 postoperative hours, daily pain scores at rest and exertion, and length of stay in the Intensive Care Unit and overall hospital length of stay
3. longer-term (one, six, 12 months) cognitive, physical, and self-care functional recovery after surgery.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Delirium in Old Age
Delirium
Coronary Artery Disease
Eligibility Criteria
Inclusion Criteria:
1. ≥ 60 years of age
2. Patients undergoing cardiac surgery \[coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery\] requiring cardiopulmonary bypass
Exclusion Criteria:
1. Pre-operative left ventricular ejection fraction (LVEF) \< than 30%
2. Emergent procedures
3. Isolated aortic surgery
4. Liver dysfunction (liver enzymes \> 3 times the baseline, all patients will have a baseline liver function test information), history and exam suggestive of jaundice
5. Hypersensitivity to the study drugs
6. Active (in the past year) history of alcohol abuse (≥5 drinks per day for men or ≥ 4 drinks per day for women)
7. Any history of alcohol withdrawal or delirium tremens
8. Delirium at baseline
9. Non-English speaking
10. Prisoners
11. Physician Refusal
12. COVID-19 Positive, symptomatic
13. Co-enrollment with non-approved interventional trial
1. ≥ 60 years of age
2. Patients undergoing cardiac surgery \[coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery\] requiring cardiopulmonary bypass
Exclusion Criteria:
1. Pre-operative left ventricular ejection fraction (LVEF) \< than 30%
2. Emergent procedures
3. Isolated aortic surgery
4. Liver dysfunction (liver enzymes \> 3 times the baseline, all patients will have a baseline liver function test information), history and exam suggestive of jaundice
5. Hypersensitivity to the study drugs
6. Active (in the past year) history of alcohol abuse (≥5 drinks per day for men or ≥ 4 drinks per day for women)
7. Any history of alcohol withdrawal or delirium tremens
8. Delirium at baseline
9. Non-English speaking
10. Prisoners
11. Physician Refusal
12. COVID-19 Positive, symptomatic
13. Co-enrollment with non-approved interventional trial
Inclusion Criteria
Inclusion Criteria:
1. ≥ 60 years of age
2. Patients undergoing cardiac surgery \[coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery\] requiring cardiopulmonary bypass
1. ≥ 60 years of age
2. Patients undergoing cardiac surgery \[coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery\] requiring cardiopulmonary bypass
Gender
All
Gender Based
false
Keywords
Acetaminophen
Postoperative
Delirium
Cardiac Surgery
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
60 Years
NCT Id
NCT04093219
Org Class
Other
Org Full Name
Beth Israel Deaconess Medical Center
Org Study Id
2019-P-000758
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
PANDORA: Scheduled Prophylactic 6-hourly Intravenous Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
Primary Outcomes
Outcome Description
Occurrence of delirium on any postoperative day, as assessed using the CAM, 3D CAM, CAM Only, or CAM-ICU daily until hospital discharge.
Outcome Measure
Incidence of postoperative delirium
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Secondary Ids
Secondary Id
R01AG065554
Secondary Outcomes
Outcome Description
Charted Delirium will be used as a key secondary outcome in addition to the CAM diagnosis. Incidence in patient's chart for diagnoses synonymous with delirium or a change to the patient's baseline mental status as indicated by trigger words associated with a predictive value for delirium
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Outcome Measure
Incidence of Charted Delirium
Outcome Description
Total number of in-hospital postoperative days in which delirium is present
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month, 6 month and 1- year following the date of surgery
Outcome Measure
Duration of delirium
Outcome Description
Delirium severity is evaluated both as the peak (highest) and sum CAM-S score over all hospital days
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Outcome Measure
Severity of delirium
Outcome Description
Measured in days
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Outcome Measure
Time to onset of delirium
Outcome Description
Amount of opioid (IV morphine or hydromorphone) and oral analgesics required for pain control, reported as overall morphine equivalents. Total Morphine Equivalent is calculated as the sum of (fentanyl dose × 2.4) + (hydromorphone dose × 4) + morphine dose + (oxycodone dose × 1.5).
Outcome Time Frame
First 48 hours postoperatively
Outcome Measure
Additional postoperative analgesic requirements
Outcome Description
Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Outcome Measure
Worst daily pain scores with exertion (deep breathing and cough)
Outcome Description
Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor
Outcome Time Frame
Measured in days admitted in the ICU, an average of 2 days
Outcome Measure
Length of stay in the Intensive Care Unit (ICU)
Outcome Description
Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 5 days
Outcome Measure
Worst daily pain scores at rest
Outcome Description
Defined by the number of days admitted in the hospital following the completion of surgery.
Outcome Time Frame
Measured in days admitted in the hospital, an average of 6 days
Outcome Measure
Length of hospital stay
Outcome Description
Neurocognition will be reported using the Montreal Cognitive Assessment (MoCA) score that ranges from zero (worst possible score) to 30 (best). At one, six, and twelve months postoperatively a telephonic MoCA will be assessed over the phone. The t-MoCA scores range from zero \[worst\] to 22 \[best\]. A hierarchical linear regression model will be used to characterize the trajectory of t-MoCA scores over time.
Outcome Time Frame
Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month, 6 month and 1- year following the date of surgery
Outcome Measure
Trajectory of cognitive function over time
Outcome Description
Physical function will be assessed using the Medical Outcomes Study Short Form 12 questionnaire (SF-12) physical composite score at one, six, and twelve months postoperatively assessed over the phone. A hierarchical linear regression model will be used to characterize the trajectory of SF-12 scores over time.
Outcome Time Frame
Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
Outcome Measure
Trajectory of physical function over time.
Outcome Description
Functional status (self care) will be assessed using the FuncAQ and FRAIL scale at one, six, and twelve months postoperatively assessed over the phone. A hierarchical linear regression model will be used to characterize the trajectory of FuncAQ and FRAIL scores over time.
Outcome Time Frame
Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
Outcome Measure
Trajectory of functional outcomes over time
Outcome Description
Chronic sternal pain will be assessed using the Numerical Pain Rating Scale (NPRS) at six and twelve months postoperatively assessed over the phone.
Outcome Time Frame
Participants will be followed at 6 month and 1- year following the date of surgery
Outcome Measure
Trajectory of chronic pain over time
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
60
Investigators
Investigator Type
Principal Investigator
Investigator Name
Matthias Eikermann
Investigator Email
meikermann@montefiore.org