Delirium in Old AgePhase 2/3NCT06653465
Intravenous Acetaminophen for Postoperative Delirium in Older Patients Recovering From Major Noncardiac Surgery
A Phase 2/3 study testing Acetaminophen and Saline in people with Delirium in Old Age, run by RenJi Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Delirium in Old Age
- What is being tested?
- Acetaminophen and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,930 participants
- Where
- No sites listed yet
- Study dates
- Jun 2025to Jul 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Age ≥ 65 years.
- Scheduled for non-cardiac major surgery with general anesthesia that is expected to last more than 2h.
- ASA Physical Status I-III.
- Weight >50 kg.
- Written informed consent.
Who cannot join
- Pre-existing neuropsychiatric diseases (Alzheimer's disease, Schizophrenia, Parkinson's Disease, Seizures, etc.).
- Pre-existing cognitive impairment (MMSE<18).
- Preoperative delirium.
- Severe circulatory instability (preoperative left ventricular ejection fraction less than 30%, unstable angina, severe coronary artery disease, sick sinus syndrome, etc.).
- Contraindication to the acetaminophen use, including serum creatinine > 177µmol/L or aminotransferses > 3 times the upper limit of normal.
- Alcohol or drug abuse within a year before surgery.
- Inability to communicate because of severe visual/auditory dysfunction or language barrier.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
Read the 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
- Being tested
- Acetaminophen, Saline
- Keywords
- postoperative delirium, acetaminophen, elderly patient
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
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.
SalineDrug
Saline, a kind of crystalloid widely used in clinical treatment.
| Study group | Role | What they receive |
|---|---|---|
| intravenous aceteminophen group | Experimental | 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. Receives: Drug: Acetaminophen |
| saline placebo group | Placebo comparator | 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. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of postoperative delirium
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.
Measured: Participants will be followed up during the first 5 postoperative days.
Secondary outcomes (5)
Delirium type
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).
Measured: Participants will be followed up during the first 5 postoperative days.
Delirium severity
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).
Measured: Participants will be followed up during the first 5 postoperative days.
Pain scores
Pain scores will be assessed using numerical rating scale (NRS) once daily, with 0 meaning "no pain" and 10 meaning "the worst pain imaginable".
Measured: Participants will be followed up during the first 5 postoperative days.
Total opioid consumption
Amount of intravenous and/or oral opioid consumption for analgesia will be recorded.
Measured: Participants will be followed up during the first 5 postoperative days.
Delirium duration
Time to onset of delirium.
Measured: Participants will be followed up during the first 5 postoperative days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study startJun 2025 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Delirium in Old AgeStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,930 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- LIQUN YANG, MD, Principal investigator, Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06653465
- Sponsor's protocol ID
- LY-2023-239
- Status last verified
- Apr 2025
- First submitted
- 20 Oct 2024
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40379334
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Acetaminophen for Postoperative Delirium in Older Patients Recovering From Major Noncardiac Surgery: a Randomised Controlled Study
- ClinicalTrials.gov ID
- NCT06653465
- Acronym / sponsor ID
- LY-2023-239
- Conditions
- Delirium in Old Age
- Keywords
- postoperative delirium, acetaminophen, elderly patient
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,930 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- Jun 2025 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 22 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intravenous aceteminophen group | Experimental | Drug: Acetaminophen50 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. |
| saline placebo group | Placebo comparator | Drug: Saline50 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- Age ≥ 65 years.
- Scheduled for non-cardiac major surgery with general anesthesia that is expected to last more than 2h.
- ASA Physical Status I-III.
- Weight >50 kg.
- Written informed consent.
Key exclusion criteria (7 listed)
- Pre-existing neuropsychiatric diseases (Alzheimer's disease, Schizophrenia, Parkinson's Disease, Seizures, etc.).
- Pre-existing cognitive impairment (MMSE<18).
- Preoperative delirium.
- Severe circulatory instability (preoperative left ventricular ejection fraction less than 30%, unstable angina, severe coronary artery disease, sick sinus syndrome, etc.).
- Contraindication to the acetaminophen use, including serum creatinine > 177µmol/L or aminotransferses > 3 times the upper limit of normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetaminophenAcetaminophen, 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. | Drug | intravenous aceteminophen group |
| SalineSaline, a kind of crystalloid widely used in clinical treatment. | Drug | saline placebo group |
Primary outcome
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.
5 secondary outcomes
Delirium type
Time frame: 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.
Pain scores
Time frame: 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.
Delirium duration
Time frame: Participants will be followed up during the first 5 postoperative days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Derived from this study: PubMed 40379334Zheng 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
LIQUN YANG, MD principal investigator
Anesthesiology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai, China
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Acetaminophen and Saline in people with Delirium in Old Age, run by RenJi Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact LIQUN YANG, MD (15921969001, lqyang72721@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative delirium (time frame: Participants will be followed up during the first 5 postoperative days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06653465, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025.