AnesthesiaNCT06980688
The PROTECT Trial: PROpofol Titration to Enhance haemodynamiC sTability
A study testing Propofol titration and Conventional propofol induction in people with Anesthesia, run by University Hospital, Basel, Switzerland at 4 sites in Switzerland.
Trial summary
The aim of this multicentre, single-blinded, expertise-based randomised controlled trial is evaluate whether slowly increasing the dose of the anaesthetic drug propofol based on a patient's needs leads to more stable blood pressure compared to giving a standard starting dose in patients aged 55 and older undergoing… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Anesthesia
- What is being tested?
- Propofol titration and Conventional propofol induction
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 4 sitesSwitzerland
- Study dates
- 2 Sep 2025to Sep 2027
- Phase
- Interventional
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 55 years old
- Patients undergoing any of the following planned surgery under general anaesthesia with intubation: Ear, nose and throat, gynaecological, maxillofacial, orthopedic, plastic and reconstructive, spine, urologic, vascular (varicose vein surgery, femoral endarterectomy, peripheral bypass surgery) and visceral surgery
- Standard procedure for anaesthesia with propofol Target-Controlled Infusion (TCI) using the Schnider model and remifentanil TCI using the Minto model
- American Society of Anesthesiologists Physical Status Classification system (ASA PS) I-IV
- Body mass index (BMI) ≥18.5 or <35 kg/m2
- Signed written informed consent
Who cannot join
- Special forms of anaesthesia induction, specifically awake tracheal intubation and rapid sequence induction
- Combined anaesthesia procedures (general and regional anaesthesia combined)
- Special forms of general anaesthesia (opioid-free anaesthesia or any opioid-sparring modifications with lidocaine, magnesium, ketamine, clonidine or dexmedetomidine)
- Surgery in the prone position within the first 30 minutes
- Patients with known difficult airway
- Daily consumption of alcohol (> one unit/day) or > seven units/week
Show all 12Show fewer
- Any regular recreational drug abuse
- Chronic use of benzodiazepines or opioids
- Allergy to propofol
- Patients with known brain pathologies, specifically seizure disorders, stroke within the past 9 months or dementia
- History of awareness
- Inability to follow procedures or insufficient knowledge in German
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland4 sites, 4 recruiting
- Not yet recruiting
Kantonsspital Baden
Baden, 5404
Andrea Kopp Lugl, PD Dr. med., +41 56 486 13 60, andrea.kopplugli@ksb.ch
Andrea Kopp Lugl, PD Dr. med.
- Recruiting
University Hospital Basel
Basel, 4031
Martin Lohri, Dr. med., +41 61 556 52 27, martindominik.lohri@usb.ch
Salome Dell-Kuster, Prof. Dr. med
- Not yet recruiting
Cantonal Hospital Graubünden
Chur, 7000
Martin Schläpfer, Prof. Dr. med., +41 81 256 65 05, martin.schlaepfer@ksgr.ch
Martin Schläpfer, Prof. Dr. med.
- Not yet recruiting
Kantonsspital Olten, soH
Olten, 4600
Kristian Mnich, Dr. med., +41 56 486 13 60, kristian.mnich@spital.so.ch
Kristian Mnich, Dr. med.
About this study
Official title: Multicentre Single-blinded, Expertise-based RCT Comparing Haemodynamic Parameters Between Titration and Conventional Induction of General Anaesthesia With Target-controlled Infusion System in Patients Undergoing Non-cardiac Surgery
The aim of this multicentre, single-blinded, expertise-based randomised controlled trial is evaluate whether slowly increasing the dose of the anaesthetic drug propofol based on a patient's needs leads to more stable blood pressure compared to giving a standard starting dose in patients aged 55 and older undergoing non-cardiac surgery.
Read the detailed description
Propofol is a widely used anaesthetic drug known to lower blood pressure (hypotension) by relaxing blood vessels. The extent of hypotension depends on the dose and speed of propofol administration. A significant drop in blood pressure after anaesthesia is started, known as post-induction hypotension (PIH), can damage organs like the heart and kidneys, especially in older and multimorbid patients.
Target-controlled infusion (TCI) systems are commonly used to deliver anaesthetic drugs like propofol and remifentanil in a controlled way. The standard approach for starting anaesthesia (induction) is to begin with a high dose to quickly make the patient unconscious and suppress the body's response to intubation. Titration is a potentially safer alternative, where the dose is slowly increased until the patient becomes unconscious.
However, current evidence comparing the two methods is limited, especially in older patients. A small retrospective study suggested that titration improves blood pressure stability, and a survey of Swiss anaesthetists showed strong interest in this approach.
This multicentre, single-blinded, expertise-based randomised controlled trial investigates whether titration using TCI systems improves blood pressure stability in patients aged 55 and older undergoing non-cardiac surgery. The results of this trial will help to evaluate the clinical applicability and economic impact of the titration method in routine anaesthesia care and may support its future implementation into standard practice.
- Conditions
- Anesthesia
- Being tested
- Propofol titration, Conventional propofol induction
- Keywords
- Target-controlled infusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propofol titrationProcedure or surgery
Induction starts with propofol target-controlled Infusion (TCI) (Schnider model) at target effect-site drug concentration (Cet) 0.5-1.0 µg/mL and remifentanil TCI (Minto model) at Cet 0.5 ng/mL. If loss of consciousness (LOC) is not reached, propofol Cet is increased in 0.5-1.0 µg/mL steps. For intubation, remifentanil Cet increases up to 6.0 ng/mL.
Conventional propofol inductionProcedure or surgery
Induction starts with propofol TCI at Cet 4-8 µg/mL and remifentanil TCI at Cet 2.5-3.5 ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| Titration group | Experimental | Patients in the titration group undergo anaesthesia induction using a stepwise approach, where the target effect-site concentration (Cet) of propofol is incrementally increased until loss of consciousness (LOC) is achieved. Once LOC is reached, the remifentanil target concentration is elevated to mitigate the laryngeal stimulus to intubation. Receives: Procedure: Propofol titration |
| Conventional group | Other | Patients in the conventional group receive anaesthesia induction using a predefined high Cet of propofol, set above the typical level required to achieve loss of consciousness (LOC), aiming for rapid induction. After induction, the remifentanil target concentration is adjusted to mitigate the laryngeal stimulus of intubation. Receives: Procedure: Conventional propofol induction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the mean arterial pressure threshold (AUT)
The area under the mean arterial pressure (MAP)-time curve below each patient's individual baseline MAP (AUT) is measured during the first 30 minutes after the start of anaesthesia induction.
Measured: 30 min after start of induction
Secondary outcomes (15)
Maximum Deviance (maxDev)
The maximum deviation between baseline MAP and the lowest recorded MAP (maxDev) is measured during the first 30 minutes after the start of anaesthesia induction.
Measured: 30 min after start of induction
Use of vasoactive drugs
The administration of vasoactive drugs during the first 30 minutes following the start of anaesthesia induction is documented.
Measured: Up to 30 min after start of induction
Use of Trendelenburg/ lithotomy positioning
The application of Trendelenburg/lithotomy positioning, where the patient is laid flat with the legs elevated above the head during the first 30 minutes following the start of anaesthesia induction is documented. If applied, the duration of this positioning is recorded.
Measured: Up to 30 min after start of induction
Total propofol consumption
Total propofol consumption in mg/kg is assessed at loss of consciousness (LOC), during the first 30 minutes after the start of anaesthesia induction, and at skin incision.
Measured: At LOC, up to 30 min after start of induction, and at skin incision
Neurocognitive test
To assess changes in neurocognitive performance, the validated, computerised Creyos task battery is used. Changes from baseline are used to evaluate the short-term impact of anaesthesia induction method on postoperative cognition.
Measured: before surgery, 1 and 3-5 hours after recovery of consciousness (ROC)
Brice Interview
To evaluate the occurrence of intraoperative awareness, the the structured and validated Brice interview is conducted postoperatively.
Measured: 3-5 hours after ROC
Time from induction start to LOC
The time from the start of anaesthesia induction to the onset of LOC is measured. LOC is defined by the absence of response to verbal and tactile stimuli, loss of the eyelash reflex, and no reaction to a jaw thrust manoeuvre. The time to LOC will be recorded to assess the speed of induction between different anaesthesia techniques.
Measured: From induction start to LOC
Total remifentanil consumption
Total remifentanil consumption in ug/kg is assessed at LOC, during the first 30 minutes after the start of anaesthesia induction, and at skin incision.
Measured: At LOC, up to 30 min after start of induction, and at skin incision
Time from induction start to intubation
The time from the start of anaesthesia induction to successful intubation is measured.
Measured: From induction start to intubation
Signs of reaction to intubation
The occurrence of signs of reaction to intubation are recorded as yes/no. If a reaction is noted, the specific signs will be documented in free text, including but not limited to tachycardia, cough reflex, limb movement, or eye opening. This outcome will help evaluate the anaesthesia technique's ability to suppress intubation responses.
Measured: During intubation
Effect-site concentration of propofol
The effect-site concentration (Ce) of propofol is measured at LOC and ROC.
Measured: At LOC and ROC
Effect-site concentration (Ce) of remifentanil
The effect-site concentration (Ce) of remifentanil is measured at LOC and ROC.
Measured: At LOC and ROC
Duration of MAP below threshold
The time that the MAP remains below 70 mmHg and 60 mmHg during the first 30 minutes following the start of anaesthesia induction is recorded.
Measured: Up to 30 min after start of induction
Bispectral Index at skin incision
The Bispectral Index (BIS) value at the time of skin incision as a measure of the patient's level of consciousness is recorded.
Measured: At skin incision
Total opioid consumption
The total opioid consumption during the post-anaesthesia care unit (PACU) stay is recorded.
Measured: During PACU stay
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2025
- Study start2 Sep 2025
- Primary completionSep 2027 (estimated)
- Study completionSep 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 AnesthesiaStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- University of Basel, University of Zurich
- Responsible party
- Sponsor
- Investigators
- Salome Dell-Kuster, Prof. Dr. med, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06980688
- Sponsor's protocol ID
- am24DellKuster
- Status last verified
- Sep 2025
- First submitted
- 8 May 2025
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised data upon reasonable request
Publications
Funk S, Lohri MD, Kopp Lugli A, Schindler C, Wiencierz A, Mnich K, Schlapfer M, Gaberdiel AP, Puhan MA, Steiner LA, Gomes NV, Dell-Kuster S. The PROTECT trial: Effect of titrated versus conventional induction of general anaesthesia using a target-controlled infusion system on haemodynamics in patients undergoing non-cardiac surgery - protocol for a multicentre, expertise-based randomised controlled trial. BMJ Open. 2026 Jan 28;16(1):e110452. doi: 10.1136/bmjopen-2025-110452.
PubMed 41605589
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre Single-blinded, Expertise-based RCT Comparing Haemodynamic Parameters Between Titration and Conventional Induction of General Anaesthesia With Target-controlled Infusion System in Patients Undergoing Non-cardiac Surgery
- ClinicalTrials.gov ID
- NCT06980688
- Acronym / sponsor ID
- am24DellKuster
- Conditions
- Anesthesia
- Keywords
- Target-controlled infusion
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- University of Basel, University of Zurich
- Study start
- 2 Sep 2025 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 20 May 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 multicentre, single-blinded, expertise-based randomised controlled trial is evaluate whether slowly increasing the dose of the anaesthetic drug propofol based on a patient's needs leads to more stable blood pressure compared to giving a standard starting dose in patients aged 55 and older undergoing non-cardiac surgery.
Detailed description
Propofol is a widely used anaesthetic drug known to lower blood pressure (hypotension) by relaxing blood vessels. The extent of hypotension depends on the dose and speed of propofol administration. A significant drop in blood pressure after anaesthesia is started, known as post-induction hypotension (PIH), can damage organs like the heart and kidneys, especially in older and multimorbid patients.
Target-controlled infusion (TCI) systems are commonly used to deliver anaesthetic drugs like propofol and remifentanil in a controlled way. The standard approach for starting anaesthesia (induction) is to begin with a high dose to quickly make the patient unconscious and suppress the body's response to intubation. Titration is a potentially safer alternative, where the dose is slowly increased until the patient becomes unconscious.
However, current evidence comparing the two methods is limited, especially in older patients. A small retrospective study suggested that titration improves blood pressure stability, and a survey of Swiss anaesthetists showed strong interest in this approach.
This multicentre, single-blinded, expertise-based randomised controlled trial investigates whether titration using TCI systems improves blood pressure stability in patients aged 55 and older undergoing non-cardiac surgery. The results of this trial will help to evaluate the clinical applicability and economic impact of the titration method in routine anaesthesia care and may support its future implementation into standard practice.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Titration group | Experimental | Procedure: Propofol titrationPatients in the titration group undergo anaesthesia induction using a stepwise approach, where the target effect-site concentration (Cet) of propofol is incrementally increased until loss of consciousness (LOC) is achieved. Once LOC is reached, the remifentanil target concentration is elevated to mitigate the laryngeal stimulus to intubation. |
| Conventional group | Other | Procedure: Conventional propofol inductionPatients in the conventional group receive anaesthesia induction using a predefined high Cet of propofol, set above the typical level required to achieve loss of consciousness (LOC), aiming for rapid induction. After induction, the remifentanil target concentration is adjusted to mitigate the laryngeal stimulus of intubation. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults ≥ 55 years old
- Patients undergoing any of the following planned surgery under general anaesthesia with intubation: Ear, nose and throat, gynaecological, maxillofacial, orthopedic, plastic and reconstructive, spine, urologic, vascular (varicose vein surgery, femoral endarterectomy, peripheral bypass surgery) and visceral surgery
- Standard procedure for anaesthesia with propofol Target-Controlled Infusion (TCI) using the Schnider model and remifentanil TCI using the Minto model
- American Society of Anesthesiologists Physical Status Classification system (ASA PS) I-IV
- Body mass index (BMI) ≥18.5 or <35 kg/m2
Key exclusion criteria (12 listed)
- Special forms of anaesthesia induction, specifically awake tracheal intubation and rapid sequence induction
- Combined anaesthesia procedures (general and regional anaesthesia combined)
- Special forms of general anaesthesia (opioid-free anaesthesia or any opioid-sparring modifications with lidocaine, magnesium, ketamine, clonidine or dexmedetomidine)
- Surgery in the prone position within the first 30 minutes
- Patients with known difficult airway
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 |
|---|---|---|
| Propofol titrationInduction starts with propofol target-controlled Infusion (TCI) (Schnider model) at target effect-site drug concentration (Cet) 0.5-1.0 µg/mL and remifentanil TCI (Minto model) at Cet 0.5 ng/mL. If loss of consciousness (LOC) is not reached, propofol Cet is increased in 0.5-1.0 µg/mL steps. For intubation, remifentanil Cet increases up to 6.0 ng/mL. | Procedure or surgery | Titration group |
| Conventional propofol inductionInduction starts with propofol TCI at Cet 4-8 µg/mL and remifentanil TCI at Cet 2.5-3.5 ng/mL. | Procedure or surgery | Conventional group |
Primary outcome
Area under the mean arterial pressure threshold (AUT)
Time frame: 30 min after start of induction
The area under the mean arterial pressure (MAP)-time curve below each patient's individual baseline MAP (AUT) is measured during the first 30 minutes after the start of anaesthesia induction.
15 secondary outcomes
Maximum Deviance (maxDev)
Time frame: 30 min after start of induction
Use of vasoactive drugs
Time frame: Up to 30 min after start of induction
Use of Trendelenburg/ lithotomy positioning
Time frame: Up to 30 min after start of induction
Total propofol consumption
Time frame: At LOC, up to 30 min after start of induction, and at skin incision
Neurocognitive test
Time frame: before surgery, 1 and 3-5 hours after recovery of consciousness (ROC)
Brice Interview
Time frame: 3-5 hours after ROC
Time from induction start to LOC
Time frame: From induction start to LOC
Total remifentanil consumption
Time frame: At LOC, up to 30 min after start of induction, and at skin incision
Time from induction start to intubation
Time frame: From induction start to intubation
Signs of reaction to intubation
Time frame: During intubation
Effect-site concentration of propofol
Time frame: At LOC and ROC
Effect-site concentration (Ce) of remifentanil
Time frame: At LOC and ROC
Duration of MAP below threshold
Time frame: Up to 30 min after start of induction
Bispectral Index at skin incision
Time frame: At skin incision
Total opioid consumption
Time frame: During PACU stay
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 19 Sep 2025.
- Derived from this study: PubMed 41605589Funk S, Lohri MD, Kopp Lugli A, Schindler C, Wiencierz A, Mnich K, Schlapfer M, Gaberdiel AP, Puhan MA, Steiner LA, Gomes NV, Dell-Kuster S. The PROTECT trial: Effect of titrated versus conventional induction of general anaesthesia using a target-controlled infusion system on haemodynamics in patients undergoing non-cardiac surgery - protocol for a multicentre, expertise-based randomised controlled trial. BMJ Open. 2026 Jan 28;16(1):e110452. doi: 10.1136/bmjopen-2025-110452.
- Individual participant dataSharing planned: Yes. Anonymised data 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.
Salome Dell-Kuster, Prof. Dr. med principal investigator
University Hospital, Basel, Switzerland
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Propofol titration and Conventional propofol induction in people with Anesthesia, run by University Hospital, Basel, Switzerland at 4 sites in Switzerland.
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 6 inclusion and 12 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 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. 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.
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 Martin Lohri, Dr. med. (+41 61 556 52 27, martindominik.lohri@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the mean arterial pressure threshold (AUT) (time frame: 30 min after start of induction). 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 NCT06980688, 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 19 Sep 2025.