Intravenous Acetaminophen for Postoperative Delirium in Older Patients Recovering From Major Noncardiac Surgery

April 1, 2025 updated by: RenJi Hospital

Intravenous Acetaminophen for Postoperative Delirium in Older Patients Recovering From Major Noncardiac Surgery: a Randomised Controlled Study

Investigators propose this multi-center randomised controlled study to test the preventive effect of intravenouse acetaminophen in delirium over 5 postoperative days among older patients recovering from major non-cardiac surgery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Delirium is a common complication in elderly patients after major surgeries and can lead to poor outcomes such as neurocognitive decline. Acetaminophen is a widely used adjuvant for perioperative multimodal analgesia. It can effectively alleviate postoperative pain, promote opioid-sparing and exert anti-neuroinflammatory response, showing strong potential for preventing postoperative delirium. There is evidence that intravenous acetaminophen reduces delirium in older patients following cardiac surgery, but its effectiveness is inconclusive among non-cardiac surgical patients. Investigators propose this multi-center, randomized, placebo-controlled, parallel-group trial in patients aged >65 years old scheduled for non-cardiac major surgery with general anesthesia expected to last at least 2 h. A total of 1930 elderly patients will be enrolled and randomized at 1:1 ratio to acetaminophen or saline placebo groups, stratified by age, education level, and trial site with random-sized blocking. Acetaminophen or saline will be given when the surgical suture begin at the end of surgery and thereafter a total of 7 doses within 48h after surgery. The primary outcome will be the incidence of delirium, assessed twice daily, through the five postoperative days. Secondary outcomes will include pain scores with movement, opioid use within the first 48 postoperative hours, severity of delirium, ICU and hospital lengths of stay.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1930

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 65 years.
  2. Scheduled for non-cardiac major surgery with general anesthesia that is expected to last more than 2h.
  3. ASA Physical Status I-III.
  4. Weight >50 kg.
  5. Written informed consent.

Exclusion Criteria:

  1. Pre-existing neuropsychiatric diseases (Alzheimer's disease, Schizophrenia, Parkinson's Disease, Seizures, etc.).
  2. Pre-existing cognitive impairment (MMSE<18).
  3. Preoperative delirium.
  4. Severe circulatory instability (preoperative left ventricular ejection fraction less than 30%, unstable angina, severe coronary artery disease, sick sinus syndrome, etc.).
  5. Contraindication to the acetaminophen use, including serum creatinine > 177µmol/L or aminotransferses > 3 times the upper limit of normal.
  6. Alcohol or drug abuse within a year before surgery.
  7. Inability to communicate because of severe visual/auditory dysfunction or language barrier.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: intravenous aceteminophen group
50 ml contains 500 mg of acetaminophen will be administered for the first dose when the surgical suture begin at the end of surgery and thereafter repeated every 6 hours for the following 7 doses using automatic intravenous pump (4g acetaminophen diluted with 0.9% saline to 400 ml), and every bolus of 50 ml will be finished within 10 minutes.
Drug: Acetaminophen
Acetaminophen, which has similarly effects with NSAIDs in terms of inhibition of cyclooxygenase COX1, COX2 and COX3, is widely used as adjuvant for perioperative multimodal analgesia.
Placebo Comparator: saline placebo group
50 ml 0.9% saline will be administered for the first dose placebo when the surgical suture begin at the end of surgery and thereafter repeated every 6 hours for the following 7 doses using automatic intravenous pump (400ml 0.9% saline without acetaminophen), and every bolus of 50 ml will be finished within 10 minutes.
Drug: Saline
Saline, a kind of crystalloid widely used in clinical treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of postoperative delirium
Time Frame: Participants will be followed up during the first 5 postoperative days.
Delirium will be assessed by the trained investigators twice daily, from 8-10 AM and from 5-7 PM, starting from postoperative day 1 using 3-minute Confusion Assessment Method (3D-CAM) or CAM-ICU for intubated patients. Immediately before assessing delirium, sedation or agitation was assessed using Richmond Agitation-Sedation Scale (RASS). If the patient was too deeply sedated or unarousable (RASS -4 or -5), delirium assessment was aborted and the patient was recorded as comatose.
Participants will be followed up during the first 5 postoperative days.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pain scores
Time Frame: Participants will be followed up during the first 5 postoperative days.
Pain scores will be assessed using numerical rating scale (NRS) once daily, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable".
Participants will be followed up during the first 5 postoperative days.
Total opioid consumption
Time Frame: Participants will be followed up during the first 5 postoperative days.
Amount of intravenous and/or oral opioid consumption for analgesia will be recorded.
Participants will be followed up during the first 5 postoperative days.
Delirium duration
Time Frame: Participants will be followed up during the first 5 postoperative days.
Time to onset of delirium.
Participants will be followed up during the first 5 postoperative days.
Delirium type
Time Frame: Participants will be followed up during the first 5 postoperative days.
Patients with delirium were classified into three motoric subtypes. Hyperactive delirium was defined when RASS was consistently positive (+1 to +4); hypoactive delirium was defined when RASS was consistently neutral or negative (-3 to 0); and mixed delirium was defined when some RASS scores were positive (+1 to +4) and some RASS scores were neutral or negative (-3 to 0).
Participants will be followed up during the first 5 postoperative days.
Delirium severity
Time Frame: Participants will be followed up during the first 5 postoperative days.
Delirium rating scale 98 revised (DRS-R-98) will be used to evaluate severity of delirium. DRS-R-98 consists of 16 items, including 13 items to assess severity of delirium and 3 diagnostic items. The total severity score range from zero (best) to 39 (worst).
Participants will be followed up during the first 5 postoperative days.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Length of days in ICU and hospital after surgery
Time Frame: one month
Length of stay in ICU and hospital after surgery will be collected from electronic medical records.
one month
All cause mortality
Time Frame: one month
one month
Cognitive function
Time Frame: Cognitive function will be evaluated on the fifth day after operation.
Cognitive function will be evaluated with Mini-Mental State Examination (MMSE) score that ranges from zero (worst) to 30 (best).
Cognitive function will be evaluated on the fifth day after operation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RenJi Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: LIQUN YANG, MD, Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 20, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LY-2023-239

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol and statistical analysis plan will be shared in peer-reviewed academic journals. Other IPD will be made available from the principal investigator upon reasonable request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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