The PROTECT Trial: PROpofol Titration to Enhance haemodynamiC sTability

NCT ID: NCT06980688

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-02
• Study Completion Date: 2027-09-30

Brief 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 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.

Conditions

Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Titration group

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.

Group Type: EXPERIMENTAL

Propofol titration

Intervention Type: PROCEDURE

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 group

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.

Group Type: OTHER

Conventional propofol induction

Intervention Type: PROCEDURE

Induction starts with propofol TCI at Cet 4-8 µg/mL and remifentanil TCI at Cet 2.5-3.5 ng/mL.

Interventions

Propofol titration

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.

Intervention Type: PROCEDURE

Conventional propofol induction

Induction starts with propofol TCI at Cet 4-8 µg/mL and remifentanil TCI at Cet 2.5-3.5 ng/mL.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Basel

OTHER

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Salome Dell-Kuster, Prof. Dr. med

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

Kantonsspital Baden

Baden, , Switzerland

Site Status: NOT_YET_RECRUITING

University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Cantonal Hospital Graubünden

Chur, , Switzerland

Site Status: NOT_YET_RECRUITING

Kantonsspital Olten, soH

Olten, , Switzerland

Site Status: NOT_YET_RECRUITING

Countries

Switzerland

Central Contacts

Martin Lohri, Dr. med.

Role: CONTACT

martindominik.lohri@usb.ch

+41 61 556 52 27

Facility Contacts

Andrea Kopp Lugl, PD Dr. med.

Role: primary

andrea.kopplugli@ksb.ch

+41 56 486 13 60

Martin Lohri, Dr. med.

Role: primary

martindominik.lohri@usb.ch

+41 61 556 52 27

Martin Schläpfer, Prof. Dr. med.

Role: primary

martin.schlaepfer@ksgr.ch

+41 81 256 65 05

Kristian Mnich, Dr. med.

Role: primary

kristian.mnich@spital.so.ch

+41 56 486 13 60

Other Identifiers

am24DellKuster

Identifier Type: -

Identifier Source: org_study_id