Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery

NCT02546765 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2014P000413
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will assess the incidence and duration of postoperative delirium in patients ≥60 years old undergoing coronary artery bypass grafting (CABG), with/without valve surgery (aortic and/or mitral) based on different regimens for postoperative sedation and analgesia. Patients will receive either intravenous (IV) dexmedetomidine and IV acetaminophen or standard postoperative management using IV propofol with morphine or hydromorphone. The Confusion Assessment Method (CAM) will be used to assess delirium in these patients. Investigators also seek to compare postoperative (48 hours) analgesic requirements in patients with or without IV acetaminophen. Investigators will finally assess postoperative cognition in post-surgical patients up to one year post-discharge using a cognitive assessment scale.

Conditions

Delirium

Keywords

analgesics; cardiac surgery; sedation

Outcome Measures

Primary Outcomes (1)

• Incidence of Delirium

  Incidence of delirium will be analyzed between patients treated with and without IV acetaminophen, measured from 24 hours post-operation and daily until discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM).

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

Secondary Outcomes (7)

• Duration of Delirium

  Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 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 6 days

• Postoperative Opioid Consumption in Morphine Equivalents

  Participants will be followed for the first 48 hours postoperatively.

• Montreal Cognitive Assessment (MoCA)

  On the day of discharge, an average of 6 days

• Hospital Length of Stay

  Measured in days admitted in the hospital, an average of 6 days

Study Arms (4)

IV acetaminophen & IV propofol

EXPERIMENTAL

20-100 µg/kg/min IV propofol given for 4-6 hours before the patients are woken up in the ICU 1g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Drug: IV acetaminophen & IV propofol

IV acetaminophen & IV dexmedetomidine

EXPERIMENTAL

A loading infusion of 0.5 - 1 µg/kg given over 10 minutes will be administered. After the loading infusion, a maintenance infusion of 0.1-1.4 µg/kg/hr will be initiated. 1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Drug: IV acetaminophen & IV dexmedetomidine

IV propofol & placebo

ACTIVE COMPARATOR

20-100 µg/kg/min IV propofol given for 4-6 hours before the patients are woken up in the ICU Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl.

Drug: IV propofol & placebo

IV dexmedetomidine & placebo

ACTIVE COMPARATOR

0.1-1.0 µg/kg/hour IV dexmedetomidine given for 4-6 hours before the patients are woken up in the ICU Volume of the placebo (saline) will match that of i.v. acetaminophen at 100ml 0.9% NaCl.

Drug: IV dexmedetomidine & placebo

Interventions

IV acetaminophen & IV propofol DRUG

use of IV tylenol and IV propofol for pain and sedation (respectively)

Also known as: Ofirmev, Diprivan

IV acetaminophen & IV propofol

IV acetaminophen & IV dexmedetomidine DRUG

use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)

Also known as: Ofirmev, Precedex

IV acetaminophen & IV dexmedetomidine

IV propofol & placebo DRUG

use of IV propofol for sedation and morphine, the drug of choice for cardiac pain

Also known as: Diprivan

IV propofol & placebo

IV dexmedetomidine & placebo DRUG

use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain

Also known as: Precedex

IV dexmedetomidine & placebo

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 60 years of age
• Undergoing CABG with/without valve (aortic and/or mitral) procedure requiring bypass

You may not qualify if:

• Pre-operative Left Ventricular Ejection Fraction (LVEF) \< 30%
• Emergent or urgent procedures, aortic surgery
• Pre-existing cognitive impairment (defined based on a short screening assessment), Parkinson's disease, Alzheimer's disease, recent seizures (\<3 months)
• Prophylactic medications for cognitive decline
• Serum creatinine \> 2 mg/dl
• Liver dysfunction (liver enzymes \> 4x the baseline, since patients will have a baseline liver function tests), history and exam suggestive of jaundice
• Known history of alcohol or drug abuse (\>10 drinks per week)
• Hypersensitivity to any of the study drug and percutaneous procedures
• Non-English speaking

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (13)

• Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B, Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009 Jan 20;119(2):229-36. doi: 10.1161/CIRCULATIONAHA.108.795260. Epub 2008 Dec 31.

  PMID: 19118253 BACKGROUND

• Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.

  PMID: 16540616 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

• Lin YY, He B, Chen J, Wang ZN. Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? a meta-analysis. Crit Care. 2012 Sep 27;16(5):R169. doi: 10.1186/cc11646.

  PMID: 23016926 BACKGROUND

• Corbett SM, Rebuck JA, Greene CM, Callas PW, Neale BW, Healey MA, Leavitt BJ. Dexmedetomidine does not improve patient satisfaction when compared with propofol during mechanical ventilation. Crit Care Med. 2005 May;33(5):940-5. doi: 10.1097/01.ccm.0000162565.18193.e5.

  PMID: 15891317 BACKGROUND

• Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009 Nov;111(5):1075-84. doi: 10.1097/ALN.0b013e3181b6a783.

  PMID: 19786862 BACKGROUND

• Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009 May-Jun;50(3):206-17. doi: 10.1176/appi.psy.50.3.206.

  PMID: 19567759 BACKGROUND

• Dasta JF, Jacobi J, Sesti AM, McLaughlin TP. Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis. Pharmacotherapy. 2006 Jun;26(6):798-805. doi: 10.1592/phco.26.6.798.

  PMID: 16716133 BACKGROUND

• Holmer Pettersson P, Jakobsson J, Owall A. Plasma concentrations following repeated rectal or intravenous administration of paracetamol after heart surgery. Acta Anaesthesiol Scand. 2006 Jul;50(6):673-7. doi: 10.1111/j.1399-6576.2006.01043.x.

  PMID: 16987360 BACKGROUND

• Wiredu K, Mueller A, McKay TB, Behera A, Shaefi S, Akeju O. Sex Differences in the Incidence of Postoperative Delirium after Cardiac Surgery: A Pooled Analyses of Clinical Trials. Anesthesiology. 2023 Oct 1;139(4):540-542. doi: 10.1097/ALN.0000000000004656. No abstract available.

  PMID: 37535937 DERIVED

• Goncalves M, Khera T, Otu HH, Narayanan S, Dillon ST, Shanker A, Gu X, Jung Y, Ngo LH, Marcantonio ER, Libermann TA, Subramaniam B. Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions. medRxiv [Preprint]. 2023 Oct 13:2023.05.30.23289741. doi: 10.1101/2023.05.30.23289741.

  PMID: 37333093 DERIVED

• 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.

  PMID: 30778597 DERIVED

• Shankar P, Mueller A, Packiasabapathy S, Gasangwa D, Patxot M, O'Gara B, Shaefi S, Marcantonio ER, Subramaniam B. Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. Trials. 2018 Jun 22;19(1):326. doi: 10.1186/s13063-018-2718-0.

  PMID: 29929533 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Acetaminophen; Propofol; Dexmedetomidine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This single center study with restrictive inclusion may place some limitations on generalizability.

Results Point of Contact

• Title: Dr. Balachundhar Subramaniam
• Organization: Beth Israel Deaconess Medical Center

bsubrama@bidmc.harvard.edu

6176320706

Study Officials

• Balachundhar Subramaniam, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anesthesiologist

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: September 11, 2015
• Study Start: October 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: July 1, 2019
• Last Updated: April 9, 2020
• Results First Posted: January 7, 2020

Record last verified: 2020-04

Locations

US (1)