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

NCT ID: NCT04093219

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

900 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-11

Study Completion Date

2026-03-04

Brief Summary

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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

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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.

Conditions

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Delirium in Old Age Delirium Coronary Artery Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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IV Acetaminophen

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

Group Type EXPERIMENTAL

IV acetaminophen

Intervention Type DRUG

use of IV tylenol for pain

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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IV acetaminophen

use of IV tylenol for pain

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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ofirmev

Eligibility Criteria

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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
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Balachundhar Subramaniam

Associate Professor of Anesthesia

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Balachundhar Subramaniam, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of California Irvine

Irvine, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

Yale University/Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Columbia University Irving Medical Center

New York, New York, United States

Site Status

Albert Einstein College of Medicine- Montefiore

The Bronx, New York, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 17872676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24350194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22206727 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21474660 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23992774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20373345 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22762316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30778597 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24733193 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39446661 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38883767 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33692183 (View on PubMed)

Other Identifiers

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R01AG065554

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019-P-000758

Identifier Type: -

Identifier Source: org_study_id

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