Postoperative DeliriumPhase 4PAPOD-ESNCT07235995
Acetaminophen-Mannitol Injection and Postoperative Delirium
A Phase 4 study testing Acetaminophen group and Sufentanil group in people with Postoperative Delirium, run by Xiangya Hospital of Central South University at 1 site in China.
Trial summary
The aim of this multicenter randomized controlled study is to evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Postoperative Delirium
- What is being tested?
- Acetaminophen group and Sufentanil group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,092 participants
- Where
- 1 siteChina
- Study dates
- 2 Feb 2026to 30 Apr 2027
- Phase
- Phase 4
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 60 years;
- Admitted to ICU after a noncardiac surgical procedure
- Signed informed consent form
Who cannot join
- Patients who meet any of the following criteria will be excluded.
- Preoperative medical history: schizophrenia, epilepsy, Parkinson's disease, end stage renal disease, or end stage liver disease.
- Inability to communicate preoperatively due to coma, severe dementia, or language disorder.
- Patients with traumatic brain injury or undergoing neurosurgical procedures.
- Positive screening result for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methamphetamine, methadone, or methylenedioxymethamphetamine).
- Participation in another clinical study within 30 days prior to surgery, or planned concurrent participation in another clinical study.
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- Positive preoperative CAM-ICU assessment indicating delirium.
- Occurrence of intraoperative or postoperative complications before randomization, and the investigator deems the subject unsuitable for study participation.
- Hepatic dysfunction at screening, defined as ALT or AST >3× the local laboratory upper limit of normal (ULN).
- Intolerance or contraindication to acetaminophen or the protocol analgesics.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xiangya hospital
Changsha, Hunan, 410000
Milin Peng, Dr., 86+15211040348, pengmilin@csu.edu.cn
About this study
Official title: Effect of Analgesia With Acetaminophen-Mannitol Injection on Postoperative Delirium in Older Patients Undergoing Non-cardiac Surgery: Protocol for an Open-label Randomized Controlled Trial
The aim of this multicenter randomized controlled study is to evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy.
Read the detailed description
Delirium is a common complication after surgery. It is associated with increased morbidity and mortality, longer intensive care unit (ICU) and hospital stay, prolonged mechanical ventilation, higher risk of institutionalization, and higher healthcare cost. Depending on patient population and screening method, the incidence of delirium in elderly patients admitted to ICU can be as high as 58-76%. The choice of analgesics and the adequacy of pain control are among the modifiable precipitating factors for postoperative delirium (POD). Whether the use of intravenous acetaminophen decreases the occurrence of POD in older noncardiac surgical patients admitted to ICU remains inadequately studied.
Objectives: To evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy, in older noncardiac surgical patients admitted to ICU.
Study design: A randomized controlled trial. Setting: 34 ICUs from different regions across China. Patients: 1092 older patients (≥ 60 years), having noncardiac surgery and admitted to ICU after surgery, are eligible.
Intervention: Patients are randomly assigned to intravenous acetaminophen or sufentanil groups. Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group. Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group (control).
Outcomes: The primary endpoint is the incidence of delirium within the first 5 days after surgery. Delirium is assessed using the confusion assessment method for the intensive care unit (CAM-ICU).The secondary outcomes include the duration of delirium occurring within postoperative days 1-5 ;analgesic effect within postoperative days 1-5; cumulative opioid exposure during the 48-hour intervention will be reported as drug-specific cumulative doses, including scheduled sufentanil and all rescue opioids; sleep quality within postoperative days 1-5; length of postoperative ICU stay and hospital stay; incidence of non delirium complications within 30 days after surgery; in hospital and 30 day postoperative all cause mortality, and quality of life and cognitive function in 30 day postoperative survivors. Exploratory outcomes include delirium related biomarkers and neurological function tests measured on postoperative day 1.Safety outcomes include the Hepatic adverse events ,adverse event and Serious adverse event .
Predicted duration of the study: 24 months.
- Conditions
- Postoperative Delirium
- Being tested
- Acetaminophen group, Sufentanil group
- Keywords
- Postoperative delirium, Intravenous acetaminophen, Elderly, Noncardiac surgical patients
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetaminophen groupDrug
The pain in this group is controlled using acetaminophen-mannitol (Paracetamol and Maninitol Injection, Yichang Renfu Medicine Co., Ltd., China), 500 mg, intravenous bolus, every 6 hours for the first 48 hours after randomization. The severity of pain is assessed using NRS/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.
Sufentanil groupDrug
The pain in this group is controlled using sufentanil (Yichang Renfu Medicine Co., Ltd., China) intravenous infusion with a rate of 0.05 μg/kg/h. The severity of pain is assessed using NRS/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen group | Experimental | Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group Receives: Drug: Acetaminophen group |
| Sufentanil group | Active comparator | Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group Receives: Drug: Sufentanil group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of delirium
Delirium assessed using CAM-ICU every 12 hours (8am, 8 pm) during postoperative days 1-5 and RASS transform at any time
Measured: postoperative 1- 5 days
Secondary outcomes (10)
Duration of delirium
Duration of delirium, defined as the number of postoperative days/hours during which delirium is present.Delirium assessed using CAM-ICU every 12 hours (8am, 8 pm) during postoperative days 1-5 and RASS transform at any time.
Measured: postoperative 1- 5 days
Severity of pain
Severity of pain assessed using numeric rating scale (NRS)/the Critical-Care Pain Observation Tool (CPOT) , 8am and 8pm, twice a day, for 5 day.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients.The NRS scale consists of 11 points from 0 to 10, where 0 indicates "no pain" and 10 indicates "severe pain". Patients select the corresponding number based on their pain level. <4 points indicate mild pain (no impact on sleep), 4-6 points indicate moderate pain, and ≥7 points indicate severe pain (pain prevents sleep or causes waking).The CPOT (Critical-Care Pain Observation Tool): Total score range 0-8, where 0 indicates no pain and 8 indicates the worst pain.
Measured: postoperative days 1-5
opioid exposure
Cumulative opioid exposure during the 48-hour intervention will be reported as drug-specific cumulative doses, including scheduled sufentanil and all rescue opioids.
Measured: 48-hour after drug infusion
Sleep quality
Subjective quality of sleep assessed using NRS (an 11-point scale where 0 = the best sleep and 10 = the worst sleep) once daily (8:00-10:00 am) during postoperative days 1-5
Measured: postoperative days 1-5
All-cause mortality
30-days outcome (survival or death) after surgery; Patients will be assessed via phone call if they are discharged before day 30 after surgery
Measured: 30-day after surgery
Length of ICU stay
Postoperative length of ICU stay, defined as the number of days (or hours) from ICU admission to ICU discharge.
Measured: From postoperative ICU admission until ICU discharge, assessed for up to 12 months.
Length of hospital stay
Postoperative length of hospital stay, defined as the number of days/hours from surgery to hospital discharge.
Measured: From the day of surgery until hospital discharge, assessed for up to 12 months.
Incidence of non-delirium-related complications
Complications unrelated to delirium occurring within 30 days postoperatively (e.g., cardiovascular events, cerebrovascular events, renal impairment, GI complications, infections, etc.) are defined as any newly developed complications that may affect patient recovery and require therapeutic intervention (including hospital admission).
Measured: 30 days after surgery
Quality of life of 30-day survivors
Patients will be assessed with World Health Organization Quality of Life Assessment Instrument Short Form (WHOQOL-BREF) via phone call if they are discharged before day 30 after surgery The scale contains 26 items covering four domains: physiological, psychological, social relations, and environmental. It uses a 1-5-point Likert scale for scoring, and the original scores are converted into a standard score of 0-100. The higher the score, the better the quality of life.
Measured: day 30 after surgery
Cognitive function of 30-day survivors
Patients will be assessed with TICS-m via phone call if they are discharged before day 30 after surgery
Measured: day 30 after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2025
- Study start2 Feb 2026
- Primary completion31 Jan 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative DeliriumStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,092 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiangya Hospital of Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lina Zhang, MD, PhD, Xiangya Hospital of Central South University
- Investigators
- Yixiong Li, Study chair, Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07235995
- Sponsor's protocol ID
- 202510115
- Other IDs
- 202510115
- Acronym
- PAPOD-ES
- Status last verified
- Oct 2026
- First submitted
- 13 Nov 2025
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Analgesia With Acetaminophen-Mannitol Injection on Postoperative Delirium in Older Patients Undergoing Non-cardiac Surgery: Protocol for an Open-label Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07235995
- Acronym / sponsor ID
- PAPOD-ES / 202510115
- Conditions
- Postoperative Delirium
- Keywords
- Postoperative delirium, Intravenous acetaminophen, Elderly, Noncardiac surgical patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,092 participants (estimated)
- Lead sponsor
- Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 19 Nov 2025 (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.
The aim of this multicenter randomized controlled study is to evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy.
Detailed description
Delirium is a common complication after surgery. It is associated with increased morbidity and mortality, longer intensive care unit (ICU) and hospital stay, prolonged mechanical ventilation, higher risk of institutionalization, and higher healthcare cost. Depending on patient population and screening method, the incidence of delirium in elderly patients admitted to ICU can be as high as 58-76%. The choice of analgesics and the adequacy of pain control are among the modifiable precipitating factors for postoperative delirium (POD). Whether the use of intravenous acetaminophen decreases the occurrence of POD in older noncardiac surgical patients admitted to ICU remains inadequately studied.
Objectives: To evaluate the effect of an intravenous acetaminophen-mannitol opioid-sparing analgesic strategy on the cumulative incidence of POD, compared with an intravenous sufentanil-based opioid analgesic strategy, in older noncardiac surgical patients admitted to ICU.
Study design: A randomized controlled trial. Setting: 34 ICUs from different regions across China. Patients: 1092 older patients (≥ 60 years), having noncardiac surgery and admitted to ICU after surgery, are eligible.
Intervention: Patients are randomly assigned to intravenous acetaminophen or sufentanil groups. Intravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group. Intravenous sufentanil is the analgesic of choice for patients in the sufentanil group (control).
Outcomes: The primary endpoint is the incidence of delirium within the first 5 days after surgery. Delirium is assessed using the confusion assessment method for the intensive care unit (CAM-ICU).The secondary outcomes include the duration of delirium occurring within postoperative days 1-5 ;analgesic effect within postoperative days 1-5; cumulative opioid exposure during the 48-hour intervention will be reported as drug-specific cumulative doses, including scheduled sufentanil and all rescue opioids; sleep quality within postoperative days 1-5; length of postoperative ICU stay and hospital stay; incidence of non delirium complications within 30 days after surgery; in hospital and 30 day postoperative all cause mortality, and quality of life and cognitive function in 30 day postoperative survivors. Exploratory outcomes include delirium related biomarkers and neurological function tests measured on postoperative day 1.Safety outcomes include the Hepatic adverse events ,adverse event and Serious adverse event .
Predicted duration of the study: 24 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen group | Experimental | Drug: Acetaminophen groupIntravenous acetaminophen is the analgesic of choice for patients in the acetaminophen group |
| Sufentanil group | Active comparator | Drug: Sufentanil groupIntravenous sufentanil is the analgesic of choice for patients in the sufentanil group |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 60 years;
- Admitted to ICU after a noncardiac surgical procedure
- Signed informed consent form
Key exclusion criteria (10 listed)
- Patients who meet any of the following criteria will be excluded.
- Preoperative medical history: schizophrenia, epilepsy, Parkinson's disease, end stage renal disease, or end stage liver disease.
- Inability to communicate preoperatively due to coma, severe dementia, or language disorder.
- Patients with traumatic brain injury or undergoing neurosurgical procedures.
- Positive screening result for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methamphetamine, methadone, or methylenedioxymethamphetamine).
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 |
|---|---|---|
| Acetaminophen groupThe pain in this group is controlled using acetaminophen-mannitol (Paracetamol and Maninitol Injection, Yichang Renfu Medicine Co., Ltd., China), 500 mg, intravenous bolus, every 6 hours for the first 48 hours after randomization. The severity of pain is assessed using NRS/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients. | Drug | Acetaminophen group |
| Sufentanil groupThe pain in this group is controlled using sufentanil (Yichang Renfu Medicine Co., Ltd., China) intravenous infusion with a rate of 0.05 μg/kg/h. The severity of pain is assessed using NRS/CPOT every 15 minutes during the first hour after randomization with study drug infusion and then once every 12 hours needed.The NRS will be used for awake patients, and the CPOT will be used for mechanically ventilated patients. | Drug | Sufentanil group |
Primary outcome
Incidence of delirium
Time frame: postoperative 1- 5 days
Delirium assessed using CAM-ICU every 12 hours (8am, 8 pm) during postoperative days 1-5 and RASS transform at any time
10 secondary outcomes
Duration of delirium
Time frame: postoperative 1- 5 days
Severity of pain
Time frame: postoperative days 1-5
opioid exposure
Time frame: 48-hour after drug infusion
Sleep quality
Time frame: postoperative days 1-5
All-cause mortality
Time frame: 30-day after surgery
Length of ICU stay
Time frame: From postoperative ICU admission until ICU discharge, assessed for up to 12 months.
Length of hospital stay
Time frame: From the day of surgery until hospital discharge, assessed for up to 12 months.
Incidence of non-delirium-related complications
Time frame: 30 days after surgery
Quality of life of 30-day survivors
Time frame: day 30 after surgery
Cognitive function of 30-day survivors
Time frame: day 30 after surgery
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 29 Oct 2026.
- Individual participant dataSharing planned: No
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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.
Yixiong Li study chair
Central South University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetaminophen group and Sufentanil group in people with Postoperative Delirium, run by Xiangya Hospital of Central South University at 1 site in China.
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 3 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Lina Zhang, Dr. (86+15874875763, zln7095@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of delirium (time frame: postoperative 1- 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Oct 2026.