PainNCT03324269
Evaluating the Predictive Value of the Nociception Level Index NOL
A study testing NOL in people with Pain and Anesthesia, run by Université Libre de Bruxelles at 1 site in Belgium.
Trial summary
Opioids remain the cornerstone for perioperative analgesia, albeit frequently associated with side effects. Most of these side-effects are dose-dependent. Thus intra-operative monitors are necessary to measure the balance between Nociception and Anti-Nociception (NAN balance) by an adequate opioid administration. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pain, Anesthesia
- What is being tested?
- NOL
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Oct 2017to 28 Feb 2019
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing non-cardiac surgery
- Patients undergoing cardiac surgery (coronary artery bypass graft)
- Knowledge of French, English or Dutch is required.
Who cannot join
- Pregnancy
- Allergy or contraindications to one of the study drugs
- BMI >30
- History of drug and alcohol abuse,
- preoperative analgesic drug use
- Heart rhythm disturbances (Atrial fibrillation, atrial flutter).
- the use of Alpha-2 adrenergic agonists
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Predictive Value of the Nociception Level Index NOL: a Pilot Study
Opioids remain the cornerstone for perioperative analgesia, albeit frequently associated with side effects. Most of these side-effects are dose-dependent.
Thus intra-operative monitors are necessary to measure the balance between Nociception and Anti-Nociception (NAN balance) by an adequate opioid administration.
Read more
Recently the NOL monitor was released.The NoL index ranges from 0 to 100 and is based on a nonlinear combination of nociception-related physiologic variables, specifically heart rate (HR), heart rate variability at the 0.15- to 0.4-Hz band power, photoplethysmograph wave amplitude (PPGA), skin conductance level, number of skin conductance fluctuations, and their time derivatives. The NoL index estimates the nociceptive/antinociceptive state from these component measures using random forest regression.
In our department, a combination of TCI propofol (Schnider model) and remifentanil (Minto model) is used to for most of the anaesthetic procedures, including cardiac anaesthesia. Remifentanil is titrated to prevent an increase in blood pressure and hearth rhythm at noxious stimuli, such as surgical incision, and adapted following hemodynamic trend during surgery.
The hypothesis of this study is to develop a calibration test using the NOL index variation to define the individual most appropriate NAN balance using remifentanil TCI before the start of surgery and before a very strong noxious surgical stimulus such as surgical incision in non-cardiac and cardiac surgery.
Before the start of surgery, the investigators want to titrate in each patient the remifentanil Ce required to abolish the NOL index response to a calibrated noxious tetanic stimulus (Tetanus 60 mamp, 100 Hz, 30 seconds). Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision. NOL and hemodynamic responses will be recorded during the entire duration of surgery.
Study protocol amendment: validation of the calibration study: Data from the calibration phase will be used to derive a formula to predict individualised anti-nociception for incision.
- Conditions
- Pain, Anesthesia
- Being tested
- NOL
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NOLDevice
After tracheal intubation, a Tetanus test (60 mAmp,100 Hz) is done during 30 sec at remifentanil level Ce of 4 ng/ml (with starting NOL value <10). According to the NOL response: increment of 1 ng/ml of RemiCe if NOL gradient ≥ 20 / decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. During the testing period propofol Ce is fixed at the concentration associated with BIS levels between 45-60 during the first calibration.
Upon the incision and 2 minutes after skin incision, Propofol TCI (Schnider model) is adjusted to BIS between 45-60 and remifentanil Ce at which the variation of NOL index variation is less than10 units at a NOL starting value <10. MAP (mean arterial pressure), HR (heart rhythm) and NIBP (non-invasive blood pressure) will be measured.
The formula derived from the calibration phase will be tested during a single tetanic stimulation at remifentanil Ce of 4 ng/ml during the validation phase.
| Study group | Role | What they receive |
|---|---|---|
| NOL | Other | After tracheal intubation and before surgical incision, a calibration Tetanus test of 100Hz, 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done (starting NOL below 10).
According to the NOL response, there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 20 or decrement of 1 ng/ml if NOL gradient < 10. Ideal remifentanil Ce is the remifentanil Ce at which the variation of NOL index will be less than 10 units at a NOL starting value below 10. Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision. NOL and hemodynamic responses will be recorded during the entire duration of surgery. Receives: Device: NOL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Predictive value of NOL
A calibration Tetanus test of 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done when starting NOL is below 10. According to the NOL response: there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 10 or a decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. The optimal individual remifentanil level is defined as the level at which the variation of NOL index will be less than 10 units starting at a NOL value below 10. So surgical incision will be done at 'optimal individual remifentanil level' and MAP (mean artrial pressure), HR (heart rhythm), NIBP (non-invasive blood pressure) will be measured (every 3 minutes).
Measured: intra-operative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start1 Oct 2017
- Primary completion28 Feb 2019
- Study completion28 Feb 2019
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 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients undergoing non-cardiac and cardiac surgery have NOL monitoring
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université Libre de Bruxelles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sarah Saxena, Université Libre de Bruxelles
- Investigators
- Luc Barvais, Principal investigator, Université Libre de Bruxelles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03324269
- Sponsor's protocol ID
- NOL
- Status last verified
- Feb 2021
- First submitted
- 16 Oct 2017
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Perrin L, Bisdorff M, Saxena S, Tabolcea I, Huybrechts I, Van Obbergh L, Engelman E, Barvais L, Coeckelenbergh S. Predicting personalised remifentanil effect site concentration for surgical incision using the nociception level index: A prospective calibration and validation study. Eur J Anaesthesiol. 2022 Dec 1;39(12):918-927. doi: 10.1097/EJA.0000000000001751. Epub 2022 Sep 21.
PubMed 36125017
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Predictive Value of the Nociception Level Index NOL: a Pilot Study
- ClinicalTrials.gov ID
- NCT03324269
- Acronym / sponsor ID
- NOL
- Conditions
- Pain, Anesthesia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Université Libre de BruxellesUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 27 Oct 2017 (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.
Opioids remain the cornerstone for perioperative analgesia, albeit frequently associated with side effects. Most of these side-effects are dose-dependent.
Thus intra-operative monitors are necessary to measure the balance between Nociception and Anti-Nociception (NAN balance) by an adequate opioid administration.
Recently the NOL monitor was released.The NoL index ranges from 0 to 100 and is based on a nonlinear combination of nociception-related physiologic variables, specifically heart rate (HR), heart rate variability at the 0.15- to 0.4-Hz band power, photoplethysmograph wave amplitude (PPGA), skin conductance level, number of skin conductance fluctuations, and their time derivatives. The NoL index estimates the nociceptive/antinociceptive state from these component measures using random forest regression.
In our department, a combination of TCI propofol (Schnider model) and remifentanil (Minto model) is used to for most of the anaesthetic procedures, including cardiac anaesthesia. Remifentanil is titrated to prevent an increase in blood pressure and hearth rhythm at noxious stimuli, such as surgical incision, and adapted following hemodynamic trend during surgery.
The hypothesis of this study is to develop a calibration test using the NOL index variation to define the individual most appropriate NAN balance using remifentanil TCI before the start of surgery and before a very strong noxious surgical stimulus such as surgical incision in non-cardiac and cardiac surgery.
Before the start of surgery, the investigators want to titrate in each patient the remifentanil Ce required to abolish the NOL index response to a calibrated noxious tetanic stimulus (Tetanus 60 mamp, 100 Hz, 30 seconds). Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision. NOL and hemodynamic responses will be recorded during the entire duration of surgery.
Study protocol amendment: validation of the calibration study: Data from the calibration phase will be used to derive a formula to predict individualised anti-nociception for incision.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients undergoing non-cardiac and cardiac surgery have NOL monitoring
| Arm | Type | Receives |
|---|---|---|
| NOL | Other | Device: NOLAfter tracheal intubation and before surgical incision, a calibration Tetanus test of 100Hz, 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done (starting NOL below 10). According to the NOL response, there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 20 or decrement of 1 ng/ml if NOL gradient < 10. Ideal remifentanil Ce is the remifentanil Ce at which the variation of NOL index will be less than 10 units at a NOL starting value below 10. Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision. NOL and hemodynamic responses will be recorded during the entire duration of surgery. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients undergoing non-cardiac surgery
- Patients undergoing cardiac surgery (coronary artery bypass graft)
- Knowledge of French, English or Dutch is required.
Key exclusion criteria (7 listed)
- Pregnancy
- Allergy or contraindications to one of the study drugs
- BMI >30
- History of drug and alcohol abuse,
- preoperative analgesic drug use
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 |
|---|---|---|
| NOLAfter tracheal intubation, a Tetanus test (60 mAmp,100 Hz) is done during 30 sec at remifentanil level Ce of 4 ng/ml (with starting NOL value <10). According to the NOL response: increment of 1 ng/ml of RemiCe if NOL gradient ≥ 20 / decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. During the testing period propofol Ce is fixed at the concentration associated with BIS levels between 45-60 during the first calibration. Upon the incision and 2 minutes after skin incision, Propofol TCI (Schnider model) is adjusted to BIS between 45-60 and remifentanil Ce at which the variation of NOL index variation is less than10 units at a NOL starting value <10. MAP (mean arterial pressure), HR (heart rhythm) and NIBP (non-invasive blood pressure) will be measured. The formula derived from the calibration phase will be tested during a single tetanic stimulation at remifentanil Ce of 4 ng/ml during the validation phase. | Device | NOL |
Primary outcome
Predictive value of NOL
Time frame: intra-operative
A calibration Tetanus test of 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done when starting NOL is below 10. According to the NOL response: there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 10 or a decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. The optimal individual remifentanil level is defined as the level at which the variation of NOL index will be less than 10 units starting at a NOL value below 10. So surgical incision will be done at 'optimal individual remifentanil level' and MAP (mean artrial pressure), HR (heart rhythm), NIBP (non-invasive blood pressure) will be measured (every 3 minutes).
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 9 Feb 2021.
- Derived from this study: PubMed 36125017Perrin L, Bisdorff M, Saxena S, Tabolcea I, Huybrechts I, Van Obbergh L, Engelman E, Barvais L, Coeckelenbergh S. Predicting personalised remifentanil effect site concentration for surgical incision using the nociception level index: A prospective calibration and validation study. Eur J Anaesthesiol. 2022 Dec 1;39(12):918-927. doi: 10.1097/EJA.0000000000001751. Epub 2022 Sep 21.
- 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.
Luc Barvais principal investigator
Université Libre de Bruxelles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NOL in people with Pain and Anesthesia, run by Université Libre de Bruxelles at 1 site in Belgium.
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 7 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 9 Feb 2021. 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 Belgium. 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?
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?
Predictive value of NOL (time frame: intra-operative). 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 NCT03324269, 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 9 Feb 2021.