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Opioid Use, UnspecifiedPhase 4ESMONOLNCT06291363

Impact of Administration of Esmolol on Nociception Level-guided Control of Nociception.

A Phase 4 study testing Esmolol Hydrochloride and Saline in people with Opioid Use, Unspecified and Anesthesia, run by Ciusss de L'Est de l'Île de Montréal at 1 site in Canada.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study aims to evaluate esmolol's perfusion impact during induction and maintenance of general anesthesia, using Nociception-Level-guided control of nociception, in adult patients undergoing laparoscopic and lower abdominal surgery, on intraoperative remifentanil consumption and postoperative pain in the… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Esmolol Hydrochloride and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
1 siteCanada
Study dates
16 Apr 2024to 4 Mar 2025
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Fully consented, American Society of Anesthesiologists Classification Score 1-3 patients from 18yo to 65yo
  • Undergoing laparoscopic surgery associated with sub umbilical mini-laparotomy. Eligible surgeries will be hysterectomy (excluding vaginal approach) and left hemicolectomy, of duration time expected under 180 minutes, under general anesthesia
  • No allergy to one of the medications used in this study

Who cannot join

  • Contraindication to the use of the study drug (esmolol) is an exclusion criterion :
  • Hypotension
  • Sinus bradycardia
  • Sick sinus syndrome
  • Second and third degree A-V block
  • Pulmonary hypertension
Show all 22Show fewer
  • Right ventricular failure secondary to pulmonary hypertension
  • Decompensated heart failure
  • Cardiogenic shock
  • Nontreated pheochromocytoma
  • Known hypersensitivity to esmolol or any of the inactive ingredients of the product
  • Allergy to esmolol or other beta blockers (cross-sensitivity is possible)
  • Renal dysfunction
  • Airway disease such as asthma or chronic obstructive pulmonary disease
  • Thyrotoxicosis
  • Myasthenia gravis
  • Raynaud's disease or peripheral circulatory disorder
  • Other situations leading to exclusion :
  • Severe mental impairment
  • Chronic use of opioids, β-adrenergic receptors antagonists
  • High risk of conversion to laparotomy according to the surgical team (>25%)
  • Patients will automatically be excluded after recruitment if they withdraw their consent, or if laparoscopy is converted to laparotomy.

Trial locations and contacts

1 site in 1 country.

Pascal Laferrière-Langlois contact

+1-819-432-5847

pascal.laferriere-langlois@umontreal.ca

Nadia Godin contact

514-252-3400 ext. 3193

ngodin.hmr@ssss.gouv.qc.ca

Canada1 site, 1 recruiting

  • Maisonneuve-Rosemont Hospital - CIUSSS de l'Est de l'Île de Montréal

    Montreal East, Quebec, H1T2M4

    Pascal Laferrière-Langois, MD FRQS, +1-819-432-5847, pascal.laferriere-langlois@umontreal.ca

    Pascal Laferrière-Langois, MD FRQS

    Recruiting

Other trials in Canada

About this study

Official title: Impact of Continuous Intraoperative Administration of Esmolol on Nociception Level-guided Control of Nociception. The EsmoNOL Randomized Controlled Trial

This study aims to evaluate esmolol's perfusion impact during induction and maintenance of general anesthesia, using Nociception-Level-guided control of nociception, in adult patients undergoing laparoscopic and lower abdominal surgery, on intraoperative remifentanil consumption and postoperative pain in the Post-Anesthesia Care Unit.

Read the detailed description

Opioids are currently the gold standard for perioperative pain control and allow for proper intraoperative hemodynamic stability. However, their use presents several major challenges, as demonstrated by the opioid crisis intensifying over the years in North America and increasingly in Europe. Besides commonly described adverse effects such as postoperative nausea, vomiting, respiratory depression, ileus, or pruritus, opioids are associated with induced hyperalgesia. In this context, several opioid-sparing strategies have been explored. The use of esmolol, a short-acting beta-blocker, can reduce sympathetic stimulation induced by perioperative nociceptive stimuli. Integrated into a multimodal strategy, it reduces the need for intraoperative opioid administration and postoperative analgesic consumption. Concurrently, multiparametric monitoring of nociception via the Nociception-Level Index (NOL index) also allows for a reduction in intraoperative opioids and decreased pain scores in the post anesthesia care unit (PACU).

The aim of this trial will be to explore the combination of these two strategies and assess the impact of continuous esmolol infusion on Nociception-Level-guided intraoperative remifentanil administration in patients under general anesthesia undergoing gynecological or general surgery via laparoscopy or lower abdominal laparotomy.

This single center randomized controlled trial will be conducted in a Canadian academic hospital. Participants aged between 18 and 65 years undergoing gynecological or general surgery by laparoscopy or lower abdominal laparotomy will be included in this study. Induction of general anesthesia will be achieved with propofol in combination with target-controlled infusion (TCI) remifentanil at 3 ng.ml-1 for intubation, then guided by the NOL Index during the procedure. Hypnosis will be maintained by the administration of sevoflurane with a target minimum alveolar concentration (MAC) between 0.7 and 1.2 to sustain a bispectral Index (BIS)between 40 and 60. Intervention group participants will receive esmolol as follows: an initial bolus of 0.5 mg.kg-1 at induction of anesthesia followed by a continuous infusion of 20mcg.kg-1.min-1 until the end of the intervention. A saline solution infusion will be administered to control group participants under the same conditions. The primary outcome will be the amount of remifentanil administered intraoperatively in mcg.kg-1.h-1. Secondary outcomes will include variations in the NOL Index during nociceptive stimuli, average heart rate and blood pressure, the intraoperative doses and time weighted average of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg), the total time and time weighted average of hypotension and or bradycardia during surgery, the time to first analgesic requirement, amount of morphine equivalent consumption for postoperative pain relief in PACU, intensity of pain at rest and under stress, using a verbal rating scale (VRS), from arrival to discharge from PACU.

The main objective of the study is to evaluate the impact of continuous intraoperative infusion of esmolol on intraoperative remifentanil administration in patients undergoing general anesthesia with NOL-guided nociception management.

Secondary objectives are listed below.

Based on a recent unpublished trial recently held at Maisonneuve-Rosemont Hospital focusing on colorectal surgeries, the investigators assumed a mean intraoperative remifentanil consumption of 5.59 mcg.kg-1.h-1 and 7.98, respectively in the intervention and control group, with a combined standard deviation of ± 3.24. This data is aligned with recently published international data. With an alpha risk of 5%, a power of 80.0%, a two-tailed test, and an estimated dropout ratio of 10.0%, it was calculated that 32 participants would be required in each group, to detect a 30% reduction in intraoperative remifentanil administration.

Study duration: 12 months

Study Center: Maisonneuve-Rosemont Hospital, Integrated University Health and Social Services Centre (CIUSSS) de l'Est de l'Ile de Montreal (CEMTL), University of Montreal, Montreal, Quebec, Canada.

Adverse Events: there is very little risk involved with participation in this study, side effects that may be associated with the use of esmolol includes bradycardia and/or hypotension

Being tested
Esmolol Hydrochloride, Saline
Keywords
opioid sparing anesthesia, beta blockers, nociception monitoring, general anesthesia
Medical subject headings
Nociceptive Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esmolol HydrochlorideDrug

    Also called Brevibloc

    Patients in the experimental group will receive esmolol during general anesthesia

  • SalineDrug

    Also called saline serum

    Patients in the standard of care group will receive saline as placebo during general anesthesia

Study groups in NCT06291363
Study groupRoleWhat they receive
EsmololExperimentalIn the Esmolol group, intravenous esmolol will be given as a bolus (0.5mg.kg-1) over 5 minutes, and will be started simultaneously to the remifentanil initiation. Once the bolus of esmolol is over, a perfusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
Receives: Drug: Esmolol Hydrochloride
Standard of carePlacebo comparatorIn the standard of care group, intravenous saline bolus, equivalent to an esmolol bolus (0.5mg.kg-1) will be given over 5 minutes, and will be started simultaneously to the remifentanil initiation. Once the bolus of saline is over, a saline perfusion equivalent to an esmolol infusion of 20 mcg.kg-1.min-1 will be programmed and maintained until the end of the surgery and completion of skin sutures
Receives: Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intra operative remifentanil administration

    Quantity of remifentanil in mcg.kg-1.h-1, administered between the first surgical incision and its discontinuation at wound dressing

    Measured: intraoperative (from T0 = incision until Tend = end of dressing)

Secondary outcomes (10)

  1. The NOL Index variation before and after orotracheal intubation and first surgical incision

    The NOL Index variation before and after orotracheal intubation and first surgical incision

    Measured: intraoperative (from T0 = nociceptive stimulation Tend = 3 minutes post stimulation)

  2. The mean intraoperative blood pressure and heart rate

    The mean intraoperative blood pressure and heart rate during surgery

    Measured: intraoperative (from T0 = incision until Tend = end of dressing)

  3. doses and time weighted of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg)

    doses and time weighted average of norepinephrine (mg); ephedrine (mg), glycopyrrolate (mg) and atropine (mg)

    Measured: intraoperative (from T0 = incision until Tend = end of dressing)

  4. Total time with NOL value above > 25

    Total time and time weighted average with NOL value above > 25

    Measured: intraoperative (from T0 = incision until Tend = end of dressing)

  5. The total time and time weighted average of hypotension and/or bradycardia

    The total time and time weighted average of hypotension (< 20% of the baseline values of the pre-anesthesia mean arterial pressure (MAP) and/or bradycardia (HR < 60 beats/min, or HR < 50 beats/min for a profound bradycardia)) during surgery

    Measured: intraoperative (from T0 = incision until Tend = end of dressing)

  6. The time to first analgesic requirement in PACU

    The time to first analgesic requirement in PACU

    Measured: postoperative (from T0 = PACU arrival until Tend = PACU discharge)

  7. The amount of morphine equivalent consumption

    The amount of morphine equivalent consumption for postoperative pain relief in the post anesthesia care unit (PACU) in both groups

    Measured: postoperative (from T0 = PACU arrival until Tend = PACU discharge)

  8. The intensity of pain at rest and under stress

    The intensity of pain at rest and under stress, using a verbal rating scale from 0 to 10 : 0 being no pain, and 10 the worst pain imaginable. I'll be assessed every 30 minutes from arrival to discharge from PACU

    Measured: postoperative (from T0 = PACU arrival until Tend = PACU discharge)

  9. Postoperative nausea and vomiting (PONV) and antiemetics use

    Postoperative outcomes such as postoperative nausea and vomiting (PONV) and amount of antiemetics used in PACU

    Measured: postoperative (from T0 = PACU arrival until Tend = PACU discharge)

  10. The time spent in PACU

    time spent in PACU (in minutes)

    Measured: postoperative (from T0 = PACU arrival until Tend = PACU discharge)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2024
  2. Study start16 Apr 2024
  3. Primary completion3 Mar 2025 (estimated)
  4. Study completion4 Mar 2025 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Two groups of patients randomized into Group "ESMOLOL" for esmolol and group "Standard of Care" for a total of 64 participants.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
64 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06291363
Sponsor's protocol ID
2024-3612
Acronym
ESMONOL
Status last verified
Jul 2024
First submitted
26 Feb 2024
Last updated
16 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.

    PubMed 16508405

  • Asouhidou I, Trikoupi A. Esmolol reduces anesthetic requirements thereby facilitating early extubation; a prospective controlled study in patients undergoing intracranial surgery. BMC Anesthesiol. 2015 Nov 28;15:172. doi: 10.1186/s12871-015-0154-1.

    PubMed 26615516

  • Bergeron C, Brulotte V, Pelen F, Clairoux A, Belanger ME, Issa R, Urbanowicz R, Tanoubi I, Drolet P, Fortier LP, Verdonck O, Fortier A, Espitalier F, Richebe P. Impact of chronic treatment by beta1-adrenergic antagonists on Nociceptive-Level (NOL) index variation after a standardized noxious stimulus under general anesthesia: a cohort study. J Clin Monit Comput. 2022 Feb;36(1):109-120. doi: 10.1007/s10877-020-00626-4. Epub 2021 Jan 4.

    PubMed 33398545

  • Bohringer C, Astorga C, Liu H. The Benefits of Opioid Free Anesthesia and the Precautions Necessary When Employing It. Transl Perioper Pain Med. 2020;7(1):152-157.

    PubMed 31712783

  • Celebi N, Cizmeci EA, Canbay O. [Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial]. Rev Bras Anestesiol. 2014 Sep-Oct;64(5):343-9. doi: 10.1016/j.bjan.2013.10.013. Epub 2014 Jun 21. Portuguese.

    PubMed 25168439

  • Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet. 2019 Apr 13;393(10180):1558-1568. doi: 10.1016/S0140-6736(19)30430-1.

    PubMed 30983591

  • Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.

    PubMed 24829420

  • Gelineau AM, King MR, Ladha KS, Burns SM, Houle T, Anderson TA. Intraoperative Esmolol as an Adjunct for Perioperative Opioid and Postoperative Pain Reduction: A Systematic Review, Meta-analysis, and Meta-regression. Anesth Analg. 2018 Mar;126(3):1035-1049. doi: 10.1213/ANE.0000000000002469.

    PubMed 29028742

  • Martini CH, Boon M, Broens SJ, Hekkelman EF, Oudhoff LA, Buddeke AW, Dahan A. Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia. Anesthesiology. 2015 Sep;123(3):524-34. doi: 10.1097/ALN.0000000000000757.

    PubMed 26154185

  • Paloheimo MP, Sahanne S, Uutela KH. Autonomic nervous system state: the effect of general anaesthesia and bilateral tonsillectomy after unilateral infiltration of lidocaine. Br J Anaesth. 2010 May;104(5):587-95. doi: 10.1093/bja/aeq065. Epub 2010 Mar 30.

    PubMed 20354006

  • Renaud-Roy E, Stockle PA, Maximos S, Brulotte V, Sideris L, Dube P, Drolet P, Tanoubi I, Issa R, Verdonck O, Fortier LP, Richebe P. Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli. Can J Anaesth. 2019 Sep;66(9):1049-1061. doi: 10.1007/s12630-019-01372-1. Epub 2019 Apr 17.

    PubMed 30997633

  • Richebe P, Capdevila X, Rivat C. Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations. Anesthesiology. 2018 Sep;129(3):590-607. doi: 10.1097/ALN.0000000000002238.

    PubMed 29738328

  • Sabourdin N, Burey J, Tuffet S, Thomin A, Rousseau A, Al-Hawari M, Taconet C, Louvet N, Constant I. Analgesia Nociception Index-Guided Remifentanil versus Standard Care during Propofol Anesthesia: A Randomized Controlled Trial. J Clin Med. 2022 Jan 11;11(2):333. doi: 10.3390/jcm11020333.

    PubMed 35054027

  • Shahiri TS, Richebe P, Richard-Lalonde M, Gelinas C. Description of the validity of the Analgesia Nociception Index (ANI) and Nociception Level Index (NOL) for nociception assessment in anesthetized patients undergoing surgery: a systematized review. J Clin Monit Comput. 2022 Jun;36(3):623-635. doi: 10.1007/s10877-021-00772-3. Epub 2021 Nov 16.

    PubMed 34783941

  • Shanthanna H, Ladha KS, Kehlet H, Joshi GP. Perioperative Opioid Administration. Anesthesiology. 2021 Apr 1;134(4):645-659. doi: 10.1097/ALN.0000000000003572.

    PubMed 32991672

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esmolol Hydrochloride and Saline in people with Opioid Use, Unspecified 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 3 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 16 Jul 2024. 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. Some participants in this study may receive a placebo. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Pascal Laferrière-Langlois (+1-819-432-5847, pascal.laferriere-langlois@umontreal.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intra operative remifentanil administration (time frame: intraoperative (from T0 = incision until Tend = end of dressing)). 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 NCT06291363, which also lists 15 linked publications.

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 16 Jul 2024.

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