Intravenous Acetaminophen After Cardiac Surgery - Definitive Study (IVACS)

Intravenous Acetaminophen After Cardiac Surgery

Double blind, double dummy trial of the use of IV acetaminophen versus oral acetaminophen for the prevention of delirium after cardiac surgery. The underlying hypothesis is that better pain control and less use of narcotics will lead to a lower incidence of delirium from day 1 to 7 following cardiac surgery. Other important secondary outcomes are the total use of narcotics, ICU and hospital stay, improved cognitive function at 6 months and 1 year post surgery, NSAID use at each centre and associated NSAID complications.

Study Overview

• Status: Recruiting
• Conditions: Post Operative Pain; Post-Op Complication; Post-cardiac Surgery; Post Operative Delirium
• Intervention / Treatment: Drug: acetaminophen

Detailed Description

Patients > or equal to 18 years of going for elective cardiac surgery will be randomized to receive IV either IV acetaminophen and an oral placebo acetaminophen or an IV placebo acetaminophen (saline) and oral acetaminophen every 6 hours for 48 hours after cardiac surgery. the study will be performed at 8 large Canadian cardiac surgery centres. All other therapy will be as per standard procedures (pragmatic) at the institutions including including use of their standard opioid protocol. The primary end-point is the development of delirium as assessed by Confusion Assessment Method in the Intensive Care unit (CAMICU) and the CAM on the regular floor unit for up to 7 days after surgery or discharge if it is sooner. Other measures are change from pre-operative cognitive function as assessed by the Montreal Cognitive Assessment score (MoCA) at 6 months and 1 year, numeric pain score, total opioid use, hospital and ICU length of stay. Use of opioids and pain score at 1 year also will be assessed. Patients will be stratified by site and sex.

We also will assess use of NSAID, specifically ketorolac, and any NSAID associated events.

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: SHELDON magder, MD; Phone Number: 5149475918; Email: sheldon.magder@mcgill.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z4
      • Active, not recruiting
      • University of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3T2N2
      • Recruiting
      • University of Manitoba
      • Contact: Rakesh Arora, MD PhD; Phone Number: 2165082112; Email: rakesh.arora@uhhospitals.org
  • Ontario
    • Mississagua, Ontario, Canada, L5B2V2
      • Not yet recruiting
      • Trillium Health Centre
      • Contact: Bill Wong, MD; Phone Number: 905-848-7178; Email: bill.wong@thp.ca
    • Ottawa, Ontario, Canada, K1N6N5
      • Not yet recruiting
      • University of Ottawa
      • Contact: Bernard McDonald, MD MSc; Phone Number: 613-612-5412; Email: Bbmcdonald@ottawaheart.ca
    • Toronto, Ontario, Canada, M4N3M5
      • Not yet recruiting
      • Sunnybroook Health Centre
      • Contact: Neill Adhikari, MD MSc; Phone Number: 416-480-4522; Email: neill.adhikari@sunnybrook.ca
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill Universtiy Health Centre
      • Contact: SHELDON magder, MD; Phone Number: 5149475918; Email: sheldon.magder@mcgill.ca
      • Contact: Rayhaneh Rahgoshai, BA; Phone Number: 5149341934
    • Montreal, Quebec, Canada, R3T2N2
      • Recruiting
      • Universite Montreal
      • Contact: Yoan Lamarche, MD, PhD; Phone Number: 514 991-3845; Email: yoanlamarche@gmail.com
    • Quebec City, Quebec, Canada, G1V0A6
      • Recruiting
      • University of Laval
      • Contact: Siamak Mohammadi, MD; Phone Number: 1 418-656-4717; Email: siamak.mohammadi@fmed.ulaval.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

greater or equal to 18

• elective cardiac surgery
• stable pre-operative
• aorto-coronary bypass with or without 1 valve replacement.

Exclusion Criteria:

Refusal by surgeon Requested late extubation by surgeon or anesthesia Intra-aortic balloon pump Mechanical cardiac support Sensitivity to acetaminophen Psychiatric history with current active treatment Alzheimer's disease Seizure in previous 6 months Recent history of alcohol misuse Cognitive impairment

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Placebo; Subject receives active intravenous acetaminophen and oral placebo acetaminophen	Drug: acetaminophen; Patient receive IV acetaminophen (and oral placebo) or placebo IV acetaminophen and oral acetaminophen. All drugs are blinded; Other Names: placebo
Placebo Comparator: Oral Acetaminophen; Subject receives placebo IV fluid (saline) and active oral acetaminophen	Drug: acetaminophen; Patient receive IV acetaminophen (and oral placebo) or placebo IV acetaminophen and oral acetaminophen. All drugs are blinded; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
post operative delirium	measured with CAMICU or CAM	up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total use of opioids	measured for 7 days or until hospital discharge	up to 7 days
Cognitive function at 6 months and 1 year	Measured with Montreal Cognitive assessment score.	6 months and 1 year
Time in intensive care unit	measured in hours	up to 7 days
time in hospital	measured in days	up to 7 days
time to extubation	measured in hours	up to 7 days

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Sunnybrook Health Sciences Centre; University of British Columbia; University of Ottawa; Laval University; Université de Montréal; St. Boniface Hospital; Trillium Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; pain; acetaminophen; narcotic; post-operative care
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Pain; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pain, Postoperative; Emergence Delirium; Postoperative Complications; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: MUHC-ACETAMINOPHEN FULL STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If the investigators of PANDORA complete their study we would request to combine our studies in a meta-analysis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No