Skip to main content
OpenTrials
Completed

NCT Number: NCT04093219

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

About this study

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;

  • the incidence, duration, and severity of postoperative delirium,
  • 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
  • longer-term (one, six, 12 months) cognitive, physical, and self-care functional recovery after surgery.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

Treatment and study plan

IV acetaminophen

Drug

use of IV tylenol for pain

Other names: ofirmev

Placebo

Other

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

Primary outcomes

  1. Incidence of postoperative delirium

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

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

Secondary outcomes

  1. Incidence of Charted Delirium

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

    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

  2. Duration of delirium

    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

    Total number of in-hospital postoperative days in which delirium is present

  3. Severity of delirium

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

    Delirium severity is evaluated both as the peak (highest) and sum CAM-S score over all hospital days

  4. Time to onset of delirium

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

    Measured in days

  5. Additional postoperative analgesic requirements

    Time frame: First 48 hours postoperatively

    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).

  6. Worst daily pain scores with exertion (deep breathing and cough)

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

    Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).

  7. Length of stay in the Intensive Care Unit (ICU)

    Time frame: Measured in days admitted in the ICU, an average of 2 days

    Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor

  8. Worst daily pain scores at rest

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

    Pain scores will be collected three times daily using a numeric rating scale (0, no pain, to 10, worst possible pain).

  9. Length of hospital stay

    Time frame: Measured in days admitted in the hospital, an average of 6 days

    Defined by the number of days admitted in the hospital following the completion of surgery.

  10. Trajectory of cognitive function over time

    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

    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.

  11. Trajectory of physical function over time.

    Time frame: Participants will be followed at 1 month, 6 month and 1- year following the date of surgery

    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.

  12. Trajectory of functional outcomes over time

    Time frame: Participants will be followed at 1 month, 6 month and 1- year following the date of surgery

    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.

  13. Trajectory of chronic pain over time

    Time frame: Participants will be followed at 6 month and 1- year following the date of surgery

    Chronic sternal pain will be assessed using the Numerical Pain Rating Scale (NPRS) at six and twelve months postoperatively assessed over the phone.

Other outcomes

  1. Need for additional liver function tests

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

    Clinical request for liver function test monitoring and reported ALT and AST values will be reported as safety outcomes

  2. Discontinuation of study drug

    Time frame: 48 hours postoperatively

    Rates of clinician discontinuation of study drug.

Sponsors and collaborators

Lead sponsor

Beth Israel Deaconess Medical Center

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Official study title

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

Acronym: PANDORA

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Sep 17, 2019
Registry last updated
Apr 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.