Prevention of Organ Dysfunction and Mortality by Monitoring the Administration of Opioids and Hypnotics in Patients at High Postoperative Risk (OPTI-TWO)

February 12, 2026 updated by: Centre Hospitalier Universitaire de Saint Etienne

Prevention of Organ Dysfunction and Mortality by Monitoring the Administration of Opioids and Hypnotics in Patients at High Postoperative Risk: the Opti-Two Study. A Multi-center Controlled Randomized Study.

Intraoperative hypotension is a common situation. It increases postoperative morbidity and mortality, especially in patients at high postoperative risk undergoing high-risk surgery. Intraoperative hypotension is partly related to anesthesia, and mainly to the combined, dose-dependent, synergistic effect of hypnotics and opioids. Monitoring sedation and monitoring analgesia reduce intraoperative consumption of each anesthetic agent. To date, the beneficial effect of combined sedation and analgesia monitoring on the reduction of intraoperative hypotension has only been found in one study, involving major abdominal surgery. Up to now, no study has been designed to demonstrate the benefit of monitoring the two components of anesthesia on postoperative organ dysfunction and mortality.

The study propose to evaluate the relevance of a combined optimization of hypnotic and opioid agents on the most frequently encountered dysfunctions related to intraoperative hypotension.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1132

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80090
        • Recruiting
        • Clinique Victor Pauchet
        • Principal Investigator:
          • Pierre HUETTE, MD
      • Amiens, France, 80054
        • Recruiting
        • CHU d'Amiens Picardie
        • Principal Investigator:
          • Hervé DUPONT, MD PhD
      • Besançon, France, 25030
        • Not yet recruiting
        • CHRU De Besancon
        • Principal Investigator:
          • Guillaume BESCH, MD PhD
      • Bordeaux, France, 33300
        • Recruiting
        • Polyclinique Bordeaux Nord Aquitaine
        • Principal Investigator:
          • Philippe RICHEBE, MD, PhD
      • Clermont-Ferrand, France, 63000
        • Not yet recruiting
        • CHU Clermont-Ferrand
        • Principal Investigator:
          • Bertille PAQUETTE, MD
      • Grenoble, France, 38700
        • Not yet recruiting
        • CHU de Grenoble
        • Principal Investigator:
          • Pierre BOUZAT, MD PhD
      • Lille, France, 59037
        • Recruiting
        • CHU de Lille
        • Principal Investigator:
          • Gilles LEBUFFE, MD PhD
      • Marseille, France, 13015
        • Not yet recruiting
        • APHM - Centre Hôpital Marseille Nord
        • Principal Investigator:
          • Marc LEONE, MD PhD
      • Nantes, France, 44093
        • Not yet recruiting
        • CHU de Nantes
        • Principal Investigator:
          • Raphaël CINOTTI, MD PhD
      • Nîmes, France, 30000
        • Recruiting
        • CHU de Nîmes
        • Sub-Investigator:
          • Yann GRICOURT, MD
        • Principal Investigator:
          • Philippe CUVILLON, MD PhD
      • Paris, France, 75018
        • Recruiting
        • Hopital Bichat Claude Bernard
        • Principal Investigator:
          • Aurélie GOUEL, MD
      • Pierre-Bénite, France, 69495
        • Recruiting
        • CHU Lyon Sud
        • Principal Investigator:
          • Arnaud FRIGGERI, MD, PhD
      • Poitiers, France, 86000
        • Recruiting
        • CHU de Poitiers
        • Principal Investigator:
          • Matthieu BOISSON, MD
      • Saint-Dié, France, 88100
        • Not yet recruiting
        • Hôpital Saint Charles
        • Principal Investigator:
          • Claude MEISTELMAN, MD, PhD
      • Saint-Etienne, France, 42100
        • Recruiting
        • Chu St-Etienne
        • Sub-Investigator:
          • Serge MOLLIEX, MD, PhD
        • Principal Investigator:
          • David CHARIER, MD, PhD
      • Toulouse, France, 31059
        • Recruiting
        • CHU de Toulouse
        • Principal Investigator:
          • Fabrice FERRE, MD PhD
      • Villejuif, France, 94800
        • Not yet recruiting
        • Institut Gustave Roussy
        • Principal Investigator:
          • Cyrus MOTAMED, MD
      • Villeurbanne, France, 69100
        • Recruiting
        • Médipole Lyon Villeurbanne
        • Principal Investigator:
          • Vincent COLLANGE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • patients affiliated to the French Social Security;
  • informed and signed consent to participating in the study;
  • planned postoperative hospitalization > 48 hours;

  • patients over 75 years of age with at least one of the following postoperative risk factors:

    • ischemic coronary disease;
    • history of compensated or prior heart failure;
    • stroke;
    • significant arrhythmias: fibrillation or auricular flutter with ventricular response > 100/minute, multiform QRS complex) or cardiac conduction abnormalities (trifascicular block, auriculoventricular block of the second or third degree);
    • peripheral vascular disease;
    • chronic obstructive pulmonary disease;
    • chronic respiratory failure;
    • renal insufficiency, defined by a creatinine > 175 µmol.l-1 (2 mg.dl-1);
    • insulin therapy for diabetes;
    • active cancer;
    • chronic alcohol abuse;
    • dementia.
  • elective or emergency high-risk surgery under general anesthesia with a combination of hypnotic and opioid, and intubation or placement of a supraglottic airway control device

Non inclusion criteria:

  • Patients who meet one or more of the preoperative following criteria will not be included:
  • acute heart failure or acute myocardial infarction;
  • complete arrhythmia due to atrial fibrillation;
  • acute respiratory failure or pneumonia;
  • septic shock;
  • acute stroke;
  • cardiac surgery;
  • open chest surgery;
  • opioid free anesthesia;
  • intraoperative ketamine at a dose > 0.25 mg.kg-1; > 0.25 mg/kg or or intravenous electric syringe
  • lidocaine or dexmedetomidine by continuous infusion;
  • refusal to participate in the study;
  • patient under guardianship, conservatorship, or unable to understand the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intervention Group
Procedure: anesthesia guided by sedation and analgesia monitoring

Anesthesia guided by sedation and analgesia monitoring The level of sedation will be monitored by

  • Monitoring System BIS™ : Bispectral index (BIS) between 45 and 60 AND Suppression Ratio (SR) at 0;
  • or SedLine® Sedation Monitor : Patient State Index (PSi) between 25 and 50;
  • or Entropy Sensor™: State entropy (SE) between 45 and 60 AND Burst Suppression Ratio (BSR) at 0;

and the level of nociception by :

  • Nociception monitor PMD-200® : Nociception Level (NoL) between 10 and 25.
Placebo Comparator: Control Group
Procedure: anesthesia performed according only to the clinical judgment of the anesthetist as usual practice
Administration of anesthesia will be performed according to the clinical judgment of the anesthetist as usual practice without sedation and analgesia monitoring

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
death
Time Frame: Day 30
Day 30
Postoperative acute kidney injury (PO-AKI)
Time Frame: Day 30
The PO-AKI will be defined as an increase to 1.5 times the reference level, or as more than 0.3 mg.dl-1 (i.e. 26.5 µmol.l-1) between the last preoperative value and the maximal value observed after surgery, or urine volume < 0.5 ml.kg-1.h-1 for 6 hours, according to the recommendations of the Acute Kidney Injury Network
Day 30
cardiovascular complication
Time Frame: Day 30
postoperative myocardial infarction, acute heart failure, acute/non pre-existing atrial fibrillation or flutter, cardiac arrest with successful resuscitation, coronary revascularisation
Day 30
neurological complication
Time Frame: Day 30
Stroke or transient ischemic attack
Day 30
Post-operative delirium (POD)
Time Frame: Day 30
Post-operative delirium (POD) will be evaluated using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM), appropriated and validated for the assessment of delirium in the postoperative period, or the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) for the intubated patients.
Day 30

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
doses of hypnotics administered
Time Frame: during surgery
during surgery
doses opioids administered;
Time Frame: during surgery
during surgery
number and duration of hypotensive periods
Time Frame: during surgery
an hypotensive event will be defined as a Mean Arterial Pressure (MAP) ≤ 65 mmHg.
during surgery
time spent within the desired range of sedation:
Time Frame: during surgery
Monitoring System BIS™ : Bispectral index (BIS) between 45 and 60 AND Suppression Ratio (SR) at 0 or SedLine® Sedation Monitor : Patient State Index (PSI) between 25 and 50 AND Suppression Ratio (SR) at 0 or Entropy Sensor™: State entropy (SE) between 45 and 60 AND Burst Suppression Ratio (BSR) at 0 The anesthetist will have access to the value of sedation monitoring in the "intervention" group; these data will be recorded but not available to the anesthetist in the "control" group: they will be analyzed at the end of the study to answer this point.
during surgery
time spent within the desired range of analgesia:
Time Frame: during surgery
Nociception monitor PMD-200® : Nociception Level (NOL) between 10 and 25. The anesthetist will have access to the value of sedation and analgesia monitoring in the "intervention" group; these data will be recorded but not available to the anesthetist in the "control" group: they will be analyzed at the end of the study to answer this point.
during surgery
doses of vasopressive amines (ephedrine or norepinephrine) administered;
Time Frame: during surgery
during surgery
pain ≥ 5 as assessed with the Visual Analogic Scale (VAS)
Time Frame: At 48 Hours after surgery
VAS 0 to 10 [0 corresponds to no pain - 10 corresponds to maximum pain]
At 48 Hours after surgery
dose of opioid administered;
Time Frame: At 48 Hours after surgery
At 48 Hours after surgery
incidence of awareness and recall during anesthesia (explicit memory).
Time Frame: At 48 Hours after surgery
At 48 Hours after surgery
acute respiratory failure or Acute Respiratory Distress Syndrome (ARDS)
Time Frame: Day 30
Day 30
duration of stay in Intensive Care Unit (ICU);
Time Frame: Day 30
Day 30
rate of unexpected ICU admission, or readmission
Time Frame: Day 30
Day 30
duration of hospital stay;
Time Frame: Day 30
Day 30
early hospital readmission rate
Time Frame: Day 30
Day 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire de Saint Etienne

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Direction Générale de l'Offre de Soins

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David CHARIER, MD, PhD, CHU de Saint-Etienne

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 7, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20PH283
  • ANSM (Other Identifier: 2025-A02337-42)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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