PANDORA: Scheduled Prophylactic 6-hourly Intravenous Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients

PANDORA: Delirium Prevention After Cardiac Surgery Using IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients

Sponsors

Lead sponsor: Beth Israel Deaconess Medical Center

Source Beth Israel Deaconess Medical Center
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.

Overall Status Not yet recruiting
Start Date September 2020
Completion Date October 2024
Primary Completion Date October 2024
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of postoperative delirium Participants will be followed for the duration of the hospital stay, an average of 5 days
Secondary Outcome
Measure Time Frame
Duration of delirium 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
Severity of delirium Participants will be followed for the duration of the hospital stay, an average of 5 days
Time to onset of delirium Participants will be followed for the duration of the hospital stay, an average of 5 days
Additional postoperative analgesic requirements First 48 hours postoperatively
Worst daily pain scores with exertion (deep breathing and cough) Participants will be followed for the duration of the hospital stay, an average of 5 days
Worst daily pain scores at rest Participants will be followed for the duration of the hospital stay, an average of 5 days
Length of stay in the Intensive Care Unit (ICU) Measured in days admitted in the ICU, an average of 2 days
Length of hospital stay Measured in days admitted in the hospital, an average of 6 days
Trajectory of cognitive function over time 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
Trajectory of physical function over time. Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
Trajectory of functional outcomes over time Participants will be followed at 1 month, 6 month and 1- year following the date of surgery
Trajectory of chronic pain over time Participants will be followed at 6 month and 1- year following the date of surgery
Enrollment 900
Condition
Intervention

Intervention type: Drug

Intervention name: IV acetaminophen

Description: use of IV tylenol for pain

Arm group label: IV Acetaminophen

Other name: ofirmev

Intervention type: Other

Intervention name: Placebo

Description: Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl

Arm group label: Placebo

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 > 4 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

Gender: All

Minimum age: 60 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Balachundhar Subramaniam, MD, MPH Principal Investigator Beth Israel Deaconess Medical Center
Overall Contact

Last name: Balachundhar Subramaniam, MD, MPH

Phone: 617-754-2721

Email: [email protected]

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: IV Acetaminophen

Arm group type: Experimental

Description: 1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl

Acronym PANDORA
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking description: The research pharmacists at each institution will prepare the placebo and will dispense the study drug according to treatment allocation. Treatment allocation will otherwise remain concealed from all others involved in the conduct and analysis of the trial, including those performing statistical analysis. Study participants will remain blinded throughout.

Source: ClinicalTrials.gov