Clinical trial NCT04093219: PANDORA: Delirium Prevention After Cardiac Surgery Using IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
Official title: PANDORA: Scheduled Prophylactic 6-hourly Intravenous Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Delirium in Old Age
Delirium
Coronary Artery Disease
Keywords: Acetaminophen
Postoperative
Delirium
Cardiac Surgery
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-09-17
Enrollment: 900
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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

Primary outcomes:
measure: Incidence of postoperative delirium
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
Secondary outcomes:
measure: Incidence of Charted Delirium
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Duration of delirium
timeFrame: 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
measure: Severity of delirium
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Time to onset of delirium
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Additional postoperative analgesic requirements
timeFrame: First 48 hours postoperatively
measure: Worst daily pain scores with exertion (deep breathing and cough)
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Length of stay in the Intensive Care Unit (ICU)
timeFrame: Measured in days admitted in the ICU, an average of 2 days
measure: Worst daily pain scores at rest
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Length of hospital stay
timeFrame: Measured in days admitted in the hospital, an average of 6 days
measure: Trajectory of cognitive function over time
timeFrame: 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
measure: Trajectory of physical function over time.
timeFrame: Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
measure: Trajectory of functional outcomes over time
timeFrame: Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
measure: Trajectory of chronic pain over time
timeFrame: Participants will be followed at 6 month and 1- year following the date of surgery
Other outcomes:
measure: Need for additional liver function tests
timeFrame: Participants will be followed for the duration of the hospital stay, an average of 5 days
measure: Discontinuation of study drug
timeFrame: 48 hours postoperatively
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale University/Yale New Haven Hospital
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Bronx
country: United States
facility: Albert Einstein College of Medicine- Montefiore
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Balachundhar Subramaniam, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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citation: Khera T, Mathur PA, Banner-Goodspeed VM, Narayanan S, Mcgourty M, Kelly L, Palihnich K, Novack L, Davis R, Talmor D, Marcantonio ER, Subramaniam B. Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial. BMJ Open. 2021 Mar 10;11(3):e044346. doi: 10.1136/bmjopen-2020-044346.