Nociceptive PainPhase 4PROSEVNOLNCT04567160
NOL Index to Compare the Intraoperative Analgesic Effect of Propofol Versus Sevoflurane
A Phase 4 study testing Propofol and Sevoflurane in people with Nociceptive Pain and Anesthesia, run by Ciusss de L'Est de l'Île de Montréal at 1 site in Canada.
Trial summary
The purpose of this prospective randomized controlled study is to compare the analgesic properties of propofol and sevoflurane using variation of the NOL index and standard monitoring (Heart Rate and Mean Arterial Blood Pressure) when patients under general anaesthesia with either agents are subjected to a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nociceptive Pain, Anesthesia
- What is being tested?
- Propofol and Sevoflurane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- 1 Oct 2020to 17 Mar 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ASA status I, II or III
- Age 18 years or older
- Elective surgery under general anesthesia.
- Good understanding of English or French language
- Non-inclusion Criteria
- Ongoing Coronary artery disease
Show all 17Show fewer
- Patients with non-regular sinus cardiac rhythm, implanted pacemakers, prescribed antimuscarinic agents, α2-adrenergic agonists, β1-adrenergic antagonists and antiarrhythmic agents
- Emergent surgery
- Pregnancy/lactation
- Preoperative hemodynamic disturbance
- Central nervous system disorder (neurologic/head trauma/uncontrolled epileptic seizures)
- Patient refusal
- Drug or alcohol abuse within the last 6 months
- Chronic use of psychoactive drugs
- Pre-operative chronic opioid use or chronic pain, equivalent to oxycodone 20mg per oral, per day for more than 6 weeks
- History of psychiatric diseases or psychological problems
- Allergy or intolerance to any of the study drugs
Who cannot join
- Unexpected difficult airway requesting excessive, possibly painful airway manipulations.
- Intraoperative unexpected complications requiring strong hemodynamic support (transfusions, vasopressors, inotropes)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of the NOL Index to Compare the Intraoperative Analgesic Effect of Propofol Versus Sevoflurane After Standardized Stimulation in Patients Under General Anesthesia. The PROSEVNOL Study
The purpose of this prospective randomized controlled study is to compare the analgesic properties of propofol and sevoflurane using variation of the NOL index and standard monitoring (Heart Rate and Mean Arterial Blood Pressure) when patients under general anaesthesia with either agents are subjected to a standardized painful stimulus (a tetanic stimulation over the ulnar nerve at 70 mA, 100 Hz for 30 seconds).
Read the detailed description
This study proposes a research design that compare the analgesic properties of two commonly used agents for induction and maintenance of the hypnotic component of anesthesia: propofol versus sevoflurane. Using the NOL index to quantitatively monitor nociception, it is expected to see a difference in response to a standardized electrical and tetanic stimulus during general anesthesia maintained with either agents.
Hypothesis is that magnitude of the variation and/or the value of the NOL Index following a standardized nociceptive stimulus is lower when general anesthesia is based on propofol rather than on sevoflurane.
Induction of general anesthesia will differ depending in which group the patient belongs.
In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil.
In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane.
At this point, noxious stimulation will be delayed at least 10 minutes after TCI remifentanil is paused to allow for the remifentanil to be cleared out and to ensure brain-alveolar equilibration of sevoflurane (sevoflurane group).
Measurements of the NOL Index, BIS, HR and MAP start 1 minute before applying noxious stimulus (prestimulation period). Means of the data collected during that period will constitute the basal values for NOL and HR before stimulation. After this stand-by period, electric stimulation is applied. This will consist in a standardized tetanic stimulation to the ulnar nerve of the non-dominant forearm delivered by a routine nerve stimulator at a frequency of 100 Hz and a current of 70 mA for a duration of 30 seconds. Measurements of the NOL Index, BIS, HR and MAP will continue during 3 minutes after (poststimulation period). This window of recording has to be free of any other external stimulation as it could produce noise disturbance on recorded values.
After the stimulation, all the monitors will be used to guide intraoperative administration of hypnotic agents and analgesics. Total consumption of hypnotics and opioids will be recorded for the duration of surgery. Postoperative assessment of pain and opioid consumption will be done in post anesthesia care unit as exploratory outcomes.
- Conditions
- Nociceptive Pain, Anesthesia
- Being tested
- Propofol, Sevoflurane
- Keywords
- NOL index
- Medical subject headings
- Nociceptive Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil. Marsh pharmacokinetic model will be used to set the initial target predicted effect-site concentration of propofol at 3.0 mcg/ml in flash mode. Simultaneously, target-controlled infusion of remifentanil will be started to reach an initial target predicted effect-site concentration of 3 ng/mL using the Minto pharmacokinetic model.
After tracheal intubation, TCI of remifentanil is paused.
SevofluraneDrug
In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane. After tracheal intubation, TCI of remifentanil is paused.
| Study group | Role | What they receive |
|---|---|---|
| Propofol group | Active comparator | Induction and maintenance of general anesthesia using propofol Receives: Drug: Propofol |
| Sevoflurane group | Active comparator | Induction and maintenance of general anesthesia using sevoflurane Receives: Drug: Sevoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delta NOL (no unit for the NOL index)
To compare the variation of NOL (delta NOL) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Secondary outcomes (17)
Delta Heart Rate (beat per minute)
To compare the variation of heart rate after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Delta Mean Arterial Blood Pressure (unit: mmHg)
To compare the variation of mean arterial blood pressure (MABP) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Delta BIS (no unit for BIS index)
To compare the variation of bispectral index (BIS) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of NOL (no unit)
To compare the peak value of NOL after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of Heart Rate (unit: beat per minute)
To compare the peak value of heart rate after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of Mean Arterial Blood Pressure (unit: mmHg)
To compare the peak value of mean arterial blood pressure (MABP) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of BIS (no unit)
To compare the peak value of bispectral index (BIS) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
Measured: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for NOL for Propofol Versus Sevoflurane (no unit)
To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation
Measured: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for Heart Rate for Propofol Versus Sevoflurane (no unit)
To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation
Measured: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for Mean Arterial Blood Pressure for Propofol Versus Sevoflurane (no unit)
To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation
Measured: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for BIS for Propofol Versus Sevoflurane (no unit)
To compare the area under the curve between propofol and sevoflurane between the beginning of stimulation and 3 minutes after stimulation
Measured: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Total Dose of Remifentanil (unit: mcg)
Total dose of remifentanil in mcg from induction of anesthesia until tracheal extubation
Measured: Intraoperative
Total Dose of Propofol (unit: mg)
Total dose of propofol in mg from induction of anesthesia until tracheal extubation in Propofol group
Measured: Intraoperative
Total Dose of Sevoflurane (unit: mL)
Total dose of sevoflurane in mL from induction of anesthesia until tracheal extubation in Sevoflurane group
Measured: Intraoperative
Total Dose of Hydromorphone in post-anesthesia care unit (PACU) (unit: mg)
Total dose of hydromorphone in mg in post-anesthesia care unit
Measured: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
post-anesthesia care unit (PACU) Pain Scores at Rest (scale from 0 to 10)
Pain scores on a scale from 0 to 10 at rest in post-anesthesia care unit
Measured: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
post-anesthesia care unit (PACU) Pain Scores during Cough (scale from 0 to 10)
Pain scores on a scale from 0 to 10 during cough effort in post-anesthesia care unit
Measured: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start1 Oct 2020
- Primary completion17 Mar 2022
- Study completion17 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nociceptive PainStudies 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled parallel open label study
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ciusss de L'Est de l'Île de Montréal
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philippe Richebe, Ciusss de L'Est de l'Île de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04567160
- Sponsor's protocol ID
- 2021-2343
- Acronym
- PROSEVNOL
- Status last verified
- Dec 2023
- First submitted
- 21 Sep 2020
- Last updated
- 21 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- 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 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of the NOL Index to Compare the Intraoperative Analgesic Effect of Propofol Versus Sevoflurane After Standardized Stimulation in Patients Under General Anesthesia. The PROSEVNOL Study
- ClinicalTrials.gov ID
- NCT04567160
- Acronym / sponsor ID
- PROSEVNOL / 2021-2343
- Conditions
- Nociceptive Pain, Anesthesia
- Keywords
- NOL index
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ciusss de L'Est de l'Île de MontréalUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 17 Mar 2022 (actual)
- Study completion
- 17 Mar 2022 (actual)
- First posted
- 28 Sep 2020 (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 purpose of this prospective randomized controlled study is to compare the analgesic properties of propofol and sevoflurane using variation of the NOL index and standard monitoring (Heart Rate and Mean Arterial Blood Pressure) when patients under general anaesthesia with either agents are subjected to a standardized painful stimulus (a tetanic stimulation over the ulnar nerve at 70 mA, 100 Hz for 30 seconds).
Detailed description
This study proposes a research design that compare the analgesic properties of two commonly used agents for induction and maintenance of the hypnotic component of anesthesia: propofol versus sevoflurane. Using the NOL index to quantitatively monitor nociception, it is expected to see a difference in response to a standardized electrical and tetanic stimulus during general anesthesia maintained with either agents.
Hypothesis is that magnitude of the variation and/or the value of the NOL Index following a standardized nociceptive stimulus is lower when general anesthesia is based on propofol rather than on sevoflurane.
Induction of general anesthesia will differ depending in which group the patient belongs.
In the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil.
In the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane.
At this point, noxious stimulation will be delayed at least 10 minutes after TCI remifentanil is paused to allow for the remifentanil to be cleared out and to ensure brain-alveolar equilibration of sevoflurane (sevoflurane group).
Measurements of the NOL Index, BIS, HR and MAP start 1 minute before applying noxious stimulus (prestimulation period). Means of the data collected during that period will constitute the basal values for NOL and HR before stimulation. After this stand-by period, electric stimulation is applied. This will consist in a standardized tetanic stimulation to the ulnar nerve of the non-dominant forearm delivered by a routine nerve stimulator at a frequency of 100 Hz and a current of 70 mA for a duration of 30 seconds. Measurements of the NOL Index, BIS, HR and MAP will continue during 3 minutes after (poststimulation period). This window of recording has to be free of any other external stimulation as it could produce noise disturbance on recorded values.
After the stimulation, all the monitors will be used to guide intraoperative administration of hypnotic agents and analgesics. Total consumption of hypnotics and opioids will be recorded for the duration of surgery. Postoperative assessment of pain and opioid consumption will be done in post anesthesia care unit as exploratory outcomes.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized controlled parallel open label study
| Arm | Type | Receives |
|---|---|---|
| Propofol group | Active comparator | Drug: PropofolInduction and maintenance of general anesthesia using propofol |
| Sevoflurane group | Active comparator | Drug: SevofluraneInduction and maintenance of general anesthesia using sevoflurane |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- ASA status I, II or III
- Age 18 years or older
- Elective surgery under general anesthesia.
- Good understanding of English or French language
- Non-inclusion Criteria
Key exclusion criteria (2 listed)
- Unexpected difficult airway requesting excessive, possibly painful airway manipulations.
- Intraoperative unexpected complications requiring strong hemodynamic support (transfusions, vasopressors, inotropes)
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 |
|---|---|---|
| PropofolIn the propofol group, general anesthesia will be induced using target-controlled infusion (TCI) of propofol and remifentanil. Marsh pharmacokinetic model will be used to set the initial target predicted effect-site concentration of propofol at 3.0 mcg/ml in flash mode. Simultaneously, target-controlled infusion of remifentanil will be started to reach an initial target predicted effect-site concentration of 3 ng/mL using the Minto pharmacokinetic model. After tracheal intubation, TCI of remifentanil is paused. | Drug | Propofol group |
| SevofluraneIn the sevoflurane group, induction of general anesthesia will be carried out by spontaneous breathing through a mask while progressively opening up the dial of the sevoflurane vaporizer up to 8%. Like in the propofol group, target-controlled infusion of remifentanil is simultaneously started to reach an initial target predicted effect-site concentration of 3 ng/mL. Vaporizer is adjusted when gas equilibration reaches the patient-specific concentration 1.0 MAC of sevoflurane. After tracheal intubation, TCI of remifentanil is paused. | Drug | Sevoflurane group |
Primary outcome
Delta NOL (no unit for the NOL index)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
To compare the variation of NOL (delta NOL) after tetanic stimulation under general anesthesia based on propofol versus sevoflurane
17 secondary outcomes
Delta Heart Rate (beat per minute)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Delta Mean Arterial Blood Pressure (unit: mmHg)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Delta BIS (no unit for BIS index)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of NOL (no unit)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of Heart Rate (unit: beat per minute)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of Mean Arterial Blood Pressure (unit: mmHg)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Peak value of BIS (no unit)
Time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for NOL for Propofol Versus Sevoflurane (no unit)
Time frame: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for Heart Rate for Propofol Versus Sevoflurane (no unit)
Time frame: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for Mean Arterial Blood Pressure for Propofol Versus Sevoflurane (no unit)
Time frame: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Area Under the Curve for BIS for Propofol Versus Sevoflurane (no unit)
Time frame: From T0 (start stimulation) to 3 minutes after tetanic stimulation for each patient
Total Dose of Remifentanil (unit: mcg)
Time frame: Intraoperative
Total Dose of Propofol (unit: mg)
Time frame: Intraoperative
Total Dose of Sevoflurane (unit: mL)
Time frame: Intraoperative
Total Dose of Hydromorphone in post-anesthesia care unit (PACU) (unit: mg)
Time frame: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
post-anesthesia care unit (PACU) Pain Scores at Rest (scale from 0 to 10)
Time frame: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
post-anesthesia care unit (PACU) Pain Scores during Cough (scale from 0 to 10)
Time frame: From entrance in post-anesthesia care unit until post-anesthesia care unit discharge, an average of 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Propofol and Sevoflurane in people with Nociceptive Pain and Anesthesia, run by Ciusss de L'Est de l'Île de Montréal at 1 site in Canada.
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 17 inclusion and 2 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: finished, as of the sponsor's last update on 21 Dec 2023. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delta NOL (no unit for the NOL index) (time frame: From 1 minute before to 3 minutes after tetanic stimulation for each patient). 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 21 Dec 2023.