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

NCT ID: NCT06653465

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 1930 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2027-07-31

Brief Summary

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.

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.

Conditions

Delirium in Old Age

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Saline, a kind of crystalloid widely used in clinical treatment.

Interventions

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.

Intervention Type: DRUG

Saline

Saline, a kind of crystalloid widely used in clinical treatment.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

LIQUN YANG, MD

Role: PRINCIPAL_INVESTIGATOR

Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai, China

Central Contacts

LIQUN YANG, MD

Role: CONTACT

lqyang72721@126.com

15921969001

References

Zheng M, Wang B, Mao M, Wu Y, Wang Z, Yang L. Intravenous acetaminophen for postoperative delirium in older patients recovering from major non-cardiac surgery: a randomised-controlled study protocol. BMJ Open. 2025 May 15;15(5):e097079. doi: 10.1136/bmjopen-2024-097079.

Reference Type: DERIVED

PMID: 40379334 (View on PubMed)

Other Identifiers

LY-2023-239

Identifier Type: -

Identifier Source: org_study_id