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

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ClinicalTrials.gov Identifier: NCT04093219
Recruitment Status : Not yet recruiting
First Posted : September 17, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Balachundhar Subramaniam, 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.

Condition or disease Intervention/treatment Phase
Delirium in Old Age Delirium Coronary Artery Disease Drug: IV acetaminophen Other: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Primary Purpose: Prevention
Official Title: PANDORA: Scheduled Prophylactic 6-hourly Intravenous Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Arm Intervention/treatment
Experimental: IV Acetaminophen
1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively
Drug: IV acetaminophen
use of IV tylenol for pain
Other Name: ofirmev

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




Primary Outcome Measures :
  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 or CAM-ICU daily until hospital discharge


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. 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).

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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 Instrumental Activities of Daily Living (IADL) questionnaire at one, six, and twelve months postoperatively assessed over the phone. A hierarchical linear regression model will be used to characterize the trajectory of IADL scores over time.

  9. 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).

  10. 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

  11. 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


Other Outcome Measures:
  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.



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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04093219


Contacts
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Contact: Balachundhar Subramaniam, MD, MPH 617-754-2721 bsubrama@bidmc.harvard.edu

Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Balachundhar Subramaniam, MD, MPH Beth Israel Deaconess Medical Center

Publications:

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Responsible Party: Balachundhar Subramaniam, Associate Professor of Anesthesia, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT04093219     History of Changes
First Posted: September 17, 2019    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Balachundhar Subramaniam, Beth Israel Deaconess Medical Center:
Acetaminophen
Postoperative
Delirium
Cardiac Surgery
Additional relevant MeSH terms:
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Acetaminophen
Delirium
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics