Postoperative DeliriumPhase 4RAPID-IINCT05990790
The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium
A Phase 4 study testing Desflurane, Sevoflurane and Propofol in people with Postoperative Delirium and Major Noncardiac Surgery, run by Medical University of Vienna at 2 sites in Austria.
Trial summary
Patients over the age of 65 years are at increased risk for developing delirium after noncardiac surgeries, resulting in increased morbidity and mortality. The prevention of postoperative delirium has been classified as a public health priority. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Postoperative Delirium, Major Noncardiac Surgery, Postoperative Cognitive Dysfunction
- What is being tested?
- Desflurane, Sevoflurane and Propofol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,332 participants
- Where
- 2 sitesAustria
- Study dates
- 3 Sep 2023to 31 Dec 2028
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Provide written informed consent
- ≥65 years of age
- Scheduled for elective major noncardiac surgery with estimated time of surgery ≥ 2 hours
Who cannot join
- Patients undergoing emergency surgery
- BMI > 45 kg/m^2
- History of diagnosed dementia
- Language, vision, or hearing impairments that may compromise cognitive assessments
- History of malignant hyperthermia
- History of structural muscle disease
Show all 9Show fewer
- History of organ transplantation (kidney, liver, lung, heart)
- Patients undergoing hyperthermic intraperitoneal chemotherapy
- ICU patients undergoing surgery
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Austria2 sites, 2 recruiting
- Recruiting
Medical University of Innsbruck
Innsbruck, 6020
Barbara Sinner, Prof., 004351250428503, barbara.sinner@i-med.ac.at
- Recruiting
Medical University of Vienna
Vienna, 1090
Christian Reiterer, MD, 0043 1 40400 ext. 20760, christian.reiterer@meduniwien.ac.at
About this study
Official title: The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium in Elderly Patients Undergoing Moderate- to High-risk Major Noncardiac Surgery - a Prospective, Observer-blinded, Randomized, Clinical Trial
Patients over the age of 65 years are at increased risk for developing delirium after noncardiac surgeries, resulting in increased morbidity and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.
Read the detailed description
Background: Postoperative delirium occurs in approximately 25% of patients over the age of 60 years undergoing major noncardiac surgery and is significantly associated with an increase in postoperative neurocognitive decline, morbidity, and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Previous small studies compared the effect of administration of sevoflurane versus propofol for maintenance of anesthesia on postoperative delirium and found beneficial effects of volatile anesthesia for the prevention of postoperative delirium. Furthermore, in small studies the administration of desflurane led to significantly shorter recovery periods after noncardiac surgery as compared to sevoflurane. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.
Methods: We will include 1332 patients ≥ 65 years of age undergoing moderate- to high-risk major noncardiac surgery lasting at least two hours in this prospective observer-blinded randomized controlled clinical trial. After induction of anesthesia patients will be randomly assigned to receive desflurane, sevoflurane or propofol for maintenance of anesthesia. Our primary outcome will be the incidence of postoperative delirium in the first five postoperative days. Postoperative delirium will be diagnosed using the 3D-CAM or 3D-CAM-ICU in the morning and evening of the first five postoperative days as appropriate assessed by blinded study personnel. Two-interim analyses after 1/3 and 2/3 of recruitment are pre-planned.
Statistics: The primary outcome, the incidence of postoperative delirium in the first five postoperative days, will be compared between the groups using a Chi-Square-test as well as a logistic regression model for the incidence of postoperative delirium will be performed accounting for randomized group, age and other possible confounding factors.
Level of originality: Data regarding possible intraoperative interventions for the prevention of postoperative delirium are scarce. In detail, the effects of commonly used anesthetics on the incidence of postoperative delirium and neurocognitive dysfunction have only been studied in retrospective analyses or small prospective studies, which showed inconsistent results. Nevertheless, delirium is a major event after surgery and is associated with postoperative complications, worse neurocognitive recovery and increased mortality, especially in elderly patients. Thus, the results of this trial will help to choose the right anesthetic according to individual patients' requirements to reduce the risk for postoperative delirium in future.
- Being tested
- Desflurane, Sevoflurane, Propofol
- Keywords
- Propofol, Sevoflurane, Desflurane
- Medical subject headings
- Emergence Delirium, Postoperative Cognitive Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DesfluraneDrug
After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10.
SevofluraneDrug
After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10.
PropofolDrug
After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10.
| Study group | Role | What they receive |
|---|---|---|
| Desflurane Group | Experimental | After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10. Receives: Drug: Desflurane |
| Sevoflurane Group | Active comparator | After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10. Receives: Drug: Sevoflurane |
| Propofol Group | Active comparator | After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10. Receives: Drug: Propofol |
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 via 3D-cognitive assessment method (3D-CAM) test as early in the morning as practical and in the early evening for the initial five postoperative days while the patients remain hospitalized according to current recommendations. In patients in the intensive care unit (ICU), we will perform the 3D-CAM-ICU. Any positive CAM test will be considered evidence of delirium, which will be analyzed dichotomously.
Measured: First five postoperative days
Secondary outcomes (8)
Digit Symbol-Substitution-Test for the incidence of postoperative cognitive dysfunction (POCD)
POCD will be assessed using the Digit-Symbol-Substitution-Test (DSST). The occurrence of POCD will be defined when a patient has a Z score on two or all tests or the combined Z score is below -1.96 standard deviation (SD).
Measured: First five postoperative days
Trail Making Test (TMT) for the incidence of postoperative cognitive dysfunction (POCD)
POCD will be assessed using the Trail Making Test (TMT). The occurrence of POCD will be defined when a patient has a Z score on two or all tests or the combined Z score is below -1.96 standard deviation (SD).
Measured: First five postoperative days
Postoperative need of supplemental oxygen
We will record postoperative need for administration of supplemental oxygen to maintain a SpO2 of 93% during PACU or ICU stay.
Measured: During PACU/ICU stay after surgery (max. of first 24 hours after surgery)
Length of stay in ICU
Length of stay in ICU after surgery.
Measured: First 30 days after surgery
Incidence of Postoperative nausea and vomiting in the early postoperative period
Episode of nausea and/or vomiting within the first two hours after surgery
Measured: First two hours after surgery
Incidence of Postoperative nausea and vomiting in the late postoperative period
Episode of nausea and/or vomiting from two hours after surgery until the fifth postoperative day.
Measured: First five postoperative days
Intraoperative hypotension
Intraoperative duration of mean arterial pressure <65mmHg and overall amount of intraoperatively administered catecholamines (including phenylephrine, norepinephrine, epinephrine, etilefrine, ephedrine).
Measured: During surgery
Death within 5 days after surgery
Mortality in the first five postoperative days.
Measured: First five postoperative days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start3 Sep 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (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 Postoperative DeliriumStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 1,332 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University Innsbruck
- Responsible party
- Principal investigator, Christian Reiterer, Medical University of Vienna
- Investigators
- Christian Reiterer, Prof. MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05990790
- Sponsor's protocol ID
- RAPIDII_01
- Acronym
- RAPID-II
- Status last verified
- Apr 2025
- First submitted
- 17 Jul 2023
- Last updated
- 30 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Taschner A, Fleischmann E, Kabon B, Sinner B, Eckhardt C, Horvath K, Adamowitsch N, Hantakova N, Hochreiter B, Zotti O, Fraunschiel M, Graf A, Reiterer C; RAPID II Trial investigators. Effect of desflurane, sevoflurane or propofol on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery: study protocol for a prospective, randomised, observer-blinded, clinical trial (RAPID-II trial). BMJ Open. 2024 Nov 27;14(11):e092611. doi: 10.1136/bmjopen-2024-092611.
PubMed 39609026
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium in Elderly Patients Undergoing Moderate- to High-risk Major Noncardiac Surgery - a Prospective, Observer-blinded, Randomized, Clinical Trial
- ClinicalTrials.gov ID
- NCT05990790
- Acronym / sponsor ID
- RAPID-II / RAPIDII_01
- Keywords
- Propofol, Sevoflurane, Desflurane
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,332 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Medical University Innsbruck
- Study start
- 3 Sep 2023 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 14 Aug 2023 (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.
Patients over the age of 65 years are at increased risk for developing delirium after noncardiac surgeries, resulting in increased morbidity and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.
Detailed description
Background: Postoperative delirium occurs in approximately 25% of patients over the age of 60 years undergoing major noncardiac surgery and is significantly associated with an increase in postoperative neurocognitive decline, morbidity, and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Previous small studies compared the effect of administration of sevoflurane versus propofol for maintenance of anesthesia on postoperative delirium and found beneficial effects of volatile anesthesia for the prevention of postoperative delirium. Furthermore, in small studies the administration of desflurane led to significantly shorter recovery periods after noncardiac surgery as compared to sevoflurane. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.
Methods: We will include 1332 patients ≥ 65 years of age undergoing moderate- to high-risk major noncardiac surgery lasting at least two hours in this prospective observer-blinded randomized controlled clinical trial. After induction of anesthesia patients will be randomly assigned to receive desflurane, sevoflurane or propofol for maintenance of anesthesia. Our primary outcome will be the incidence of postoperative delirium in the first five postoperative days. Postoperative delirium will be diagnosed using the 3D-CAM or 3D-CAM-ICU in the morning and evening of the first five postoperative days as appropriate assessed by blinded study personnel. Two-interim analyses after 1/3 and 2/3 of recruitment are pre-planned.
Statistics: The primary outcome, the incidence of postoperative delirium in the first five postoperative days, will be compared between the groups using a Chi-Square-test as well as a logistic regression model for the incidence of postoperative delirium will be performed accounting for randomized group, age and other possible confounding factors.
Level of originality: Data regarding possible intraoperative interventions for the prevention of postoperative delirium are scarce. In detail, the effects of commonly used anesthetics on the incidence of postoperative delirium and neurocognitive dysfunction have only been studied in retrospective analyses or small prospective studies, which showed inconsistent results. Nevertheless, delirium is a major event after surgery and is associated with postoperative complications, worse neurocognitive recovery and increased mortality, especially in elderly patients. Thus, the results of this trial will help to choose the right anesthetic according to individual patients' requirements to reduce the risk for postoperative delirium in future.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Desflurane Group | Experimental | Drug: DesfluraneAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10. |
| Sevoflurane Group | Active comparator | Drug: SevofluraneAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10. |
| Propofol Group | Active comparator | Drug: PropofolAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Provide written informed consent
- ≥65 years of age
- Scheduled for elective major noncardiac surgery with estimated time of surgery ≥ 2 hours
Key exclusion criteria (9 listed)
- Patients undergoing emergency surgery
- BMI > 45 kg/m^2
- History of diagnosed dementia
- Language, vision, or hearing impairments that may compromise cognitive assessments
- History of malignant hyperthermia
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 |
|---|---|---|
| DesfluraneAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10. | Drug | Desflurane Group |
| SevofluraneAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10. | Drug | Sevoflurane Group |
| PropofolAfter induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10. | Drug | Propofol Group |
Primary outcome
Incidence of postoperative delirium
Time frame: First five postoperative days
Delirium will be assessed via 3D-cognitive assessment method (3D-CAM) test as early in the morning as practical and in the early evening for the initial five postoperative days while the patients remain hospitalized according to current recommendations. In patients in the intensive care unit (ICU), we will perform the 3D-CAM-ICU. Any positive CAM test will be considered evidence of delirium, which will be analyzed dichotomously.
8 secondary outcomes
Digit Symbol-Substitution-Test for the incidence of postoperative cognitive dysfunction (POCD)
Time frame: First five postoperative days
Trail Making Test (TMT) for the incidence of postoperative cognitive dysfunction (POCD)
Time frame: First five postoperative days
Postoperative need of supplemental oxygen
Time frame: During PACU/ICU stay after surgery (max. of first 24 hours after surgery)
Length of stay in ICU
Time frame: First 30 days after surgery
Incidence of Postoperative nausea and vomiting in the early postoperative period
Time frame: First two hours after surgery
Incidence of Postoperative nausea and vomiting in the late postoperative period
Time frame: First five postoperative days
Intraoperative hypotension
Time frame: During surgery
Death within 5 days after surgery
Time frame: First five 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 30 Apr 2025.
- Derived from this study: PubMed 39609026Taschner A, Fleischmann E, Kabon B, Sinner B, Eckhardt C, Horvath K, Adamowitsch N, Hantakova N, Hochreiter B, Zotti O, Fraunschiel M, Graf A, Reiterer C; RAPID II Trial investigators. Effect of desflurane, sevoflurane or propofol on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery: study protocol for a prospective, randomised, observer-blinded, clinical trial (RAPID-II trial). BMJ Open. 2024 Nov 27;14(11):e092611. doi: 10.1136/bmjopen-2024-092611.
- 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.
Christian Reiterer, Prof. MD principal investigator
Medical University of Vienna
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Desflurane, Sevoflurane and Propofol in people with Postoperative Delirium and Major Noncardiac Surgery, run by Medical University of Vienna at 2 sites in Austria.
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 9 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 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria. 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 Alexander Taschner, MD (0043 1 40400 ext. 20760, alexander.taschner@meduniwien.ac.at), 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: First five 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 NCT05990790, 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 30 Apr 2025.