Hyperalgesia, Persistent Pain, and Fentanyl Dosing in On-Pump Coronary Artery Bypass Grafting

June 4, 2021 updated by: University Hospital, Ghent
Randomized, double-blinded, three arm study in adult patients undergoing first time coronary artery bypass grafting (CABG) surgery with median sternotomy. The investigators will examine the effects of three fentanyl dosing schemes (high-dose bolus, low-dose bolus, continuous dose) on the area of hyperalgesia and allodynia at 24 and 48h as well as on persisting pain at 3, 6, and 12 months. Additionally, the investigators will measure fentanyl concentrations throughout anesthesia.

Study Overview

Status

Status

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

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.

Detailed Description

A prospective, randomized, double-blinded (patient, anesthesiologist, assessor) clinical study. This study will examine three different clinically used application schemes of fentanyl, an opioid used as the standard of care in routine practice. Patients will be randomized to receive one of the following three treatment arms for anesthesia maintenance (pre-sternotomy):

  1. High-dose fentanyl bolus (20 µg/kg of body weight [BW]; e.g. 70kg 1400 µg or 1.4mg)
  2. Low-dose fentanyl bolus (3 µg/kg BW; e.g. 70kg 210 µg or 0.2mg)

  3. Continuous fentanyl application by Shibutani scheme

    This study will include data from 69 adult patients (23 per arm) undergoing first time, elective, on-pump CABG surgery with median sternotomy and central cannulation.

    Following randomization by the sealed envelope technique, fentanyl kits will be drawn up by an anesthesiologist not involved in patient care or outcome assessment. Patients with preexisting chronic pain, opioids in the last 30 days, a BMI>36kg/m2, sleep apnoea, renal failure (clearance <30ml/min), with neuraxial anesthesia, pregnant, with planned wound infiltration, known allergies/intolerance to opioids, and unable to understand pin-prick testing will be excluded.

    At induction, all patients will receive a standard 3 µg/kg bolus of fentanyl (not study medication, but rather standard of care). 5 minutes prior to sternotomy, the patient will receive analgesia maintenance (one of the three fentanyl study arms). Clinicians will at all times be able to administer a bolus of fentanyl on a perceived "as needed" basis (not study medication, but rather standard of care).

    The primary objective of this trial is to assess whether or not different intraoperative dosing schemes of fentanyl during on-pump CABG surgery influence the area of hyperalgesia as measured by sternal pin-prick testing on the first postoperative day. As the mechanisms causing opioid-induced analgesia are poorly understood but appear to be dosis-related, the investigators will examine 3 clinically used fentanyl application schemes in cardiac surgery: 1) a high-dose bolus group, 2) a low-dose bolus group, and 3) a low-dose continuous infusion group.

    [i.e. does fentanyl dosing influence the area of hyperalgesia?]

    The secondary objectives of this trial are 1) to explore the intraoperative concentrations of fentanyl in these various dosing schemes during and after extracorporeal circulation (ECC).

    [i.e. determine the time course of fentanyl with ECC and its association with hyperalgesia; explorative] 2) to explore a possible association between fentanyl dosing, hyperalgesia, and persisting pain 3, 6, and 12 months after surgery.

    [i.e. clinical implication on persistent/chronic pain; explorative]

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 (Actual)

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.
80

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.
  • Phase 4

Contacts and Locations

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

Study Locations

  • Belgium
    • Oost-Vlaanderen
      • Ghent, Oost-Vlaanderen, Belgium, 9000
        • University Hospital Ghent

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Consenting patients aged ≥18 years
  • Undergoing first-time, elective, on-pump CABG surgery with median sternotomy and central cannulation.

Exclusion Criteria:

  • Documentation of preexisting chronic pain as per electronic record
  • Use of opioids in the last 30 days or history/documentation of opioid abuse as per electronic record
  • BMI > 35kg/m2 or history of obstructive sleep apnea syndrome
  • Patients with renal failure (clearance < 30 ml/min)
  • Neuraxial anesthesia
  • Pregnancy
  • Planned wound infiltration with local anesthetics
  • Known drug allergies or intolerance to fentanyl or other opioids
  • Expected to be unable to understand pinprick/allodynia testing / follow-up questions

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: Single Group Assignment
  • Masking: Quadruple

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: High-Dose Bolus of Fentanyl

5 minutes prior to sternotomy, patients will receive a fentanyl bolus of 20 mcg/kg BW (verum) and a perfusion pump with sodium chloride (NaCl 0.9%; placebo) will be begun according to the Shibutani dosing scheme.

As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.
Drug: Fentanyl dosing schemes
We routinely use fentanyl as the opioid of choice in CABG surgery. However, how much and whether or not to apply it in boli or continuously remain uncertain. We will apply 3 routinely used fentanyl dosing schemes in our hospital. To blind care-givers and patients, in each of the arms a bolus and a continous injection will occur, as delineated in the treatment arms.
Experimental: Low-Dose Bolus of Fentanyl

5 minutes prior to sternotomy, patients will receive a fentanyl bolus of 3 mcg/kg BW (verum) and a perfusion pump with sodium chloride (NaCl 0.9%; placebo) will be begun according to the Shibutani dosing scheme.

As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.
Drug: Fentanyl dosing schemes
We routinely use fentanyl as the opioid of choice in CABG surgery. However, how much and whether or not to apply it in boli or continuously remain uncertain. We will apply 3 routinely used fentanyl dosing schemes in our hospital. To blind care-givers and patients, in each of the arms a bolus and a continous injection will occur, as delineated in the treatment arms.
Experimental: Continuous Dose of Fentanyl

5 minutes prior to sternotomy, patients will receive a NaCl 0.9% bolus (placebo) and a perfusion pump with fentanyl (verum) will be begun according to the Shibutani dosing scheme.

As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.
Drug: Fentanyl dosing schemes
We routinely use fentanyl as the opioid of choice in CABG surgery. However, how much and whether or not to apply it in boli or continuously remain uncertain. We will apply 3 routinely used fentanyl dosing schemes in our hospital. To blind care-givers and patients, in each of the arms a bolus and a continous injection will occur, as delineated in the treatment arms.

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
Area of hyperalgesia at 24h
Time Frame: 24 hours after surgery (+/- 3 hours)
Determination of secondary, wound hyperalgesia by pin prick (256mN von Frey filament)
24 hours after surgery (+/- 3 hours)

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
Area of hyperalgesia at 48h
Time Frame: 48 hours after surgery (+/- 3 hours)
Determination of secondary, wound hyperalgesia by pin prick (256mN von Frey filament)
48 hours after surgery (+/- 3 hours)
Area of allodynia at 24h
Time Frame: 24 hours after surgery (+/- 3 hours)
Determination of allodynia by cotton swab
24 hours after surgery (+/- 3 hours)
Area of allodynia at 48h
Time Frame: 48 hours after surgery (+/- 3 hours)
Determination of allodynia by cotton swab
48 hours after surgery (+/- 3 hours)
Persistent Pain at 3 months
Time Frame: 3 months after surgery (+/- 1 week)
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
3 months after surgery (+/- 1 week)
Persistent Pain at 6 months
Time Frame: 6 months after surgery (+/- 1 week)
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
6 months after surgery (+/- 1 week)
Persistent Pain at 12 months
Time Frame: 12 months after surgery (+/- 1 week)
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
12 months after surgery (+/- 1 week)
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 5 min. (+/- 1 min) prior to sternotomy, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run as specified by the time frame of this outcome and the following outcomes.
5 min. (+/- 1 min) prior to sternotomy, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 5 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Fentanyl will be measured from samples taken prior to, during, and after a pump run
5 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 30 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Fentanyl will be measured from samples taken prior to, during, and after a pump run
30 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: just prior (<1min) to start of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
just prior (<1min) to start of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 5 min. (+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
5 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 20 min. (+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
20 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 40 min.(+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
40 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 60 min.(+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
60 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 80 min. (+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
80 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 100 min. (+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
100 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 120 min.(+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
120 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 140 min.(+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
140 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 160 min.(+/- 1 min) after begin of pump run, a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
160 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: 5 min.(+/- 1 min) after end of pump run,a surgical step
Fentanyl will be measured from samples taken prior to, during, and after a pump run
5 min.(+/- 1 min) after end of pump run,a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Time Frame: end of surgery (+/- 5 min)
Fentanyl will be measured from samples taken prior to, during, and after a pump run
end of surgery (+/- 5 min)

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.
University Hospital, Ghent

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.
University Hospital, Basel, Switzerland

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.
May 14, 2018

Primary Completion (Actual)

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, 2020

Study Completion (Actual)

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.
January 9, 2021

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).
January 29, 2018

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.
February 28, 2018

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.
March 1, 2018

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.
June 7, 2021

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.
June 4, 2021

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.
December 1, 2018

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.
  • AGO/2017/005
  • 2017-003278-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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