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

NCT04093219 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 2019-P-000758R01AG065554
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 10

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.

Conditions

Coronary Artery Disease; Delirium in Old Age; Delirium

Keywords

Acetaminophen; Postoperative; Delirium; Cardiac Surgery

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium

  Occurrence of delirium on any postoperative day, as assessed using the CAM, 3D CAM, CAM Only, or CAM-ICU daily until hospital discharge.

  Participants will be followed for the duration of the hospital stay, an average of 5 days

Secondary Outcomes (13)

• Incidence of Charted Delirium

  Participants will be followed for the duration of the hospital stay, an average of 5 days

• 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

Other Outcomes (2)

• Need for additional liver function tests

  Participants will be followed for the duration of the hospital stay, an average of 5 days

• Discontinuation of study drug

  48 hours postoperatively

Study Arms (2)

IV Acetaminophen

EXPERIMENTAL

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

Drug: IV acetaminophen

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Placebo OTHER

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

Placebo

IV acetaminophen DRUG

use of IV tylenol for pain

Also known as: ofirmev

IV Acetaminophen

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 60 years of age
• Patients undergoing cardiac surgery \[coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery\] requiring cardiopulmonary bypass

You may not qualify if:

• Pre-operative left ventricular ejection fraction (LVEF) \< than 30%
• Emergent procedures
• Isolated aortic surgery
• Liver dysfunction (liver enzymes \> 3 times the baseline, all patients will have a baseline liver function test information), history and exam suggestive of jaundice
• Hypersensitivity to the study drugs
• Active (in the past year) history of alcohol abuse (≥5 drinks per day for men or ≥ 4 drinks per day for women)
• Any history of alcohol withdrawal or delirium tremens
• Delirium at baseline
• Non-English speaking
• Prisoners
• Physician Refusal
• COVID-19 Positive, symptomatic
• Co-enrollment with non-approved interventional trial

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Institute on Aging (NIA): collaborator

Study Sites (10)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Yale University/Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Albert Einstein College of Medicine- Montefiore

The Bronx, New York, 10467, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (12)

• Rudolph JL, Marcantonio ER. Review articles: postoperative delirium: acute change with long-term implications. Anesth Analg. 2011 May;112(5):1202-11. doi: 10.1213/ANE.0b013e3182147f6d. Epub 2011 Apr 7.

  BACKGROUND

• Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28.

  BACKGROUND

• Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Selnes OA, McKhann GM. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol. 2010 Mar;67(3):338-44. doi: 10.1002/ana.21899.

  BACKGROUND

• Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.

  PMID: 22762316 BACKGROUND

• van den Boogaard M, Kox M, Quinn KL, van Achterberg T, van der Hoeven JG, Schoonhoven L, Pickkers P. Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care. 2011;15(6):R297. doi: 10.1186/cc10598. Epub 2011 Dec 29.

  BACKGROUND

• Gallagher R. Opioid-induced neurotoxicity. Can Fam Physician. 2007 Mar;53(3):426-7. No abstract available.

  BACKGROUND

• O'Neal JB. The utility of intravenous acetaminophen in the perioperative period. Front Public Health. 2013 Aug 6;1:25. doi: 10.3389/fpubh.2013.00025.

  BACKGROUND

• Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, Gallagher J, Gasangwa D, Patxot M, Packiasabapathy S, Mathur P, Eikermann M, Talmor D, Marcantonio ER. Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):686-696. doi: 10.1001/jama.2019.0234.

  BACKGROUND

• Inouye SK, Kosar CM, Tommet D, Schmitt EM, Puelle MR, Saczynski JS, Marcantonio ER, Jones RN. The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Ann Intern Med. 2014 Apr 15;160(8):526-533. doi: 10.7326/M13-1927.

  BACKGROUND

• Ramachandran RV, Behera A, Hussain Z, Peck J, Ananthakrishanan A, Mathur P, Banner-Goodspeed V, Muehlschlegel JD, Pittet JF, Bardia A, Schonberger R, Marcantonio ER, Kveraga K, Subramaniam B. Incidence of Concurrent Cerebral Desaturation and Electroencephalographic Burst Suppression in Cardiac Surgery Patients. Anesth Analg. 2025 May 1;140(5):1086-1092. doi: 10.1213/ANE.0000000000007209.

  PMID: 39446661 DERIVED

• Ramachandran RV, Ananthakrishnan A, Orui H, Kveraga K, Subramaniam B. The Influence of Preoperative Physical Activity on Intraoperative Brain Function in Cardiac Surgical patients. Res Sq [Preprint]. 2024 Jun 7:rs.3.rs-4427122. doi: 10.21203/rs.3.rs-4427122/v1.

  PMID: 38883767 DERIVED

• 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.

  PMID: 33692183 DERIVED

MeSH Terms

Conditions

Delirium; Coronary Artery Disease

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Balachundhar Subramaniam, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesia

Study Record Dates

• First Submitted: September 13, 2019
• First Posted: September 17, 2019
• Study Start: August 11, 2020
• Primary Completion: March 30, 2026
• Study Completion: April 5, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (10)