AnesthesiaiControl-RPNCT01771263
Closed-loop Control of Anesthesia: Controlled Delivery of Remifentanil and Propofol
A study of Anesthesia, run by Fraser Health at 1 site in Canada.
Trial summary
In closed-loop controlled anesthesia, feedback from a measure of the clinical effect is used to continuously adjust drug infusion rates. Anesthetic drugs are delivered at a variable rate that is personalized to the individual patient. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Anesthesia
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2013to Dec 2015
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 19 years of age or older
- ASA I-III
- Elective surgical procedures performed in the operating room at Royal Columbian Hospital requiring TIVA
- Ability to provide informed consent
Who cannot join
- Contra-indications to the administration of propofol and/or remifentanil:
- propofol is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products; remifentanil is contraindicated in patients with known hypersensitivity to fentanyl analogs.
- Known or suspected neurological disease
- Known abnormality in any previous EEG examination
- Chronic opioid analgesic (more than 10 doses in previous one month) or other sedative drug therapy
- Body Mass Index (BMI) < 15 or BMI > 45
- Premedication other than metoclopramide and/or ranitidine required
- Currently enrolled in another drug or device clinical trial
Trial locations and contacts
1 site in 1 country.
Canada1 site
Royal Columbian Hospital
New Westminster, British Columbia, V3L 3W7
About this study
In closed-loop controlled anesthesia, feedback from a measure of the clinical effect is used to continuously adjust drug infusion rates. Anesthetic drugs are delivered at a variable rate that is personalized to the individual patient. The aim is to provide greater hemodynamic and respiratory stability, more stable depth of anesthesia, the ability to predict recovery and to administer a lower total dose of drug. Previous work in closed-loop control of intravenous anesthesia has focused on the titration of propofol in response to a depth of hypnosis (DOH) measure derived from the electroencephalogram (EEG).
The purpose of this pilot study is to evaluate iControl-RP, a system, which performs controlled delivery of both remifentanil and propofol infusions. iControl-RP allows either drug to be operated in any of 3 modes: closed-loop control based on feedback from an EEG measure supplied by NeuroSENSE (1); target-controlled infusion (TCI), based on previously-described pharmacokinetic (PK) and pharmacodynamic (PD) models; and conventional manual infusion, which require a weight-based dose setting.
Read more
A pilot two-phase study will be undertaken in a group of adult patients under the direct and immediate supervision of an experienced anesthesiologist. In Phase 1 (involving 50 study subjects), propofol will be administered in closed-loop mode and a remifentanil infusion will be administered based on a TCI. The data collected in this phase will be used to tune the controller parameters, which are initially based on previously published PKPD data. The controller performance will then be evaluated in phase 2 (involving 100 study subjects), in which both propofol and remifentanil will be administered in closed loop mode. In both phases, cases will be selected from those receiving propofol and remifentanil as anesthetic agents for routine surgical procedures.
The investigators aim to demonstrate that closed-loop control of anesthesia and analgesia based on EEG feedback is clinically feasible. This pilot study will help us take a significant step towards a controlled trial in which the clinical benefit of this method of closed-loop control of anesthesia can be assessed.
Read the detailed description
Purpose:
The purpose of this pilot study is to demonstrate that controlled delivery of remifentanil and propofol is clinically feasible and to collect a sample of clinical data to optimise the control functions. That is,
to demonstrate that the iControl remifentanil-propofol control system (iControl-RP) can be used to provide safe and effective administration of anesthesia (while maintaining the requirement for intervention by the anaesthesiologist when necessary) to collect a sample of clinical data that will allow the ECEM engineers to optimise the parameters of the iControl-RP control system
Justification:
Closed-loop control provides an opportunity to deliver anesthetic drugs at variable rate that is personalized to the individual patient. This suggests that it may provide greater hemodynamic and respiratory stability, more stable depth of anesthesia, the ability to predict recovery and to administer a lower total dose of drug.
Much development work is still required to mesh closed-loop control technology with anesthetic practice. The results of this initial study will feed into a subsequent larger study wherein the clinical, operational and economic benefits of closed-loop control of anesthesia will be submitted to a controlled trial.
Objectives:
The primary objective of this pilot study is to demonstrate the feasibility of closed-loop control of the delivery of both propofol and remifentanil using DOH feedback from the NeuroSENSE and show that it is a safe and effective mechanism for the administration of anesthesia and analgesia in adult patients undergoing routine elective surgical procedures. The secondary objective of this pilot study is to collect a sample of clinical data to optimise the tuning parameters for this system.
Research Method:
A pilot two-phase study will be undertaken in a group of adult patients under the direct and immediate supervision of an experienced anesthesiologist:
Phase 1: tuning controller parameters Propofol infusion will be closed-loop controlled; remifentanil will run as a target-controlled infusion (TCI); this system is comparable to the system evaluated in adult patients at the Hôpital Foch, Franc. The goal of this phase is to collect data to validate the mid-ranging controller design, which is based on population-based PKPD models.
Phase 2: evaluating controller performance The mid-ranging control system will be evaluated; both propofol and remifentanil infusion rates will be closed-loop controlled.
In both phases, cases will be selected from among patients who would be receiving propofol and remifentanil as the anesthetic agents for the planned procedure.
Research procedures will be similar in the two study phases. The anesthesiologist will closely monitor the patient as per routine practice and have the ability, at any time, to modify the anesthetic/analgesic drugs being administered. That is, he/she will be able to adjust the target DOH effect; adjust the target effect site concentration for remifentanil; immediately switch to manual control of either infusion; administer a bolus dose or immediately stop the infusion of either drug.
Investigational device iControl-RP has been developed for this study by the ECEM group at UBC headed by Prof. Dumont. iControl-RP is a control system developed for automatic closed-loop drug delivery in anesthesia. In this study remifentanil will be used as the fast actuator (control of analgesia) and propofol will be use as the slow actuator (control of hypnosis). Remifentanil is used to counteract disturbances in the measured DOH related to insufficient analgesia and propofol is used to maintain a stable baseline DOH. iControl-RP is connected to the NeuroSENSE, 2 infusion pumps for separately-controlled propofol and remifentanil administration, and the operating room (OR) patient monitor. It has a user interface, which displays the WAVCNS, infusion rates and effect site concentrations for both propofol and remifentanil. The user interface allows the anesthesiologist to set the target WAVCNS, to switch between modes of operation (manual, TCI, closed-loop) and set manual infusion rates or target effect-site concentrations for either drug, as required.
The system has been extensively tested in the laboratory for usability, reliability and repeatability. The vital signs collected from the OR patient monitor provide information for safety alerts.
Health Canada Investigational approval is being sought and will be received before commencement of study.
How the system works iControl-RP controls the infusion rates of a propofol infusion pump (Alaris TIVA) and a remifentanil infusion pump (Graseby 3400). The system allows either drug infusion to be operated in any of 3 modes: closed-loop control, which relies on WAVCNS feedback from the NeuroSENSE; TCI, which is based on PKPD models; and manual, which requires a weight-based dose setting (.e.g in mcg/kg/min).
- Conditions
- Anesthesia
- Being tested
- iControl-RP
- Keywords
- Anesthesia, Propofol, Remifentanil, NeuroSENSE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iControl-RPDevice
| Study group | Role | What they receive |
|---|---|---|
| iControl-RP | Other | iControl-RP is a system which performs controlled delivery of both remifentanil and propofol infusions. Receives: Device: iControl-RP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depth of Hypnosis (WAVcns)
Depth of hypnosis measurements will be used among other parameters to assess the feasibility of the system for delivery of propofol and remifentanil for anesthesia
Measured: Continually assessed throughout anesthesia
Secondary outcomes (1)
Time until induction complete (Tind)
Time interval between propofol infusion commencing and the depth of hypnosis remaining below 60 WAVcns units for more than 30 seconds
Measured: Beginning of anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2015
- Study completionDec 2015
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 AnesthesiaStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fraser Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Merchant, Principal investigator, Royal Columbian Hospital and University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01771263
- Sponsor's protocol ID
- FHREB 2012-056
- Acronym
- iControl-RP
- Status last verified
- Aug 2014
- First submitted
- 15 Jan 2013
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
West N, van Heusden K, Gorges M, Brodie S, Rollinson A, Petersen CL, Dumont GA, Ansermino JM, Merchant RN. Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System. Anesth Analg. 2018 Oct;127(4):883-894. doi: 10.1213/ANE.0000000000002663.
PubMed 29210791
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-loop Control of Anesthesia: Controlled Delivery of Remifentanil and Propofol
- ClinicalTrials.gov ID
- NCT01771263
- Acronym / sponsor ID
- iControl-RP / FHREB 2012-056
- Conditions
- Anesthesia
- Keywords
- Anesthesia, Propofol, Remifentanil, NeuroSENSE
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Fraser HealthUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 18 Jan 2013 (estimated)
- 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.
In closed-loop controlled anesthesia, feedback from a measure of the clinical effect is used to continuously adjust drug infusion rates. Anesthetic drugs are delivered at a variable rate that is personalized to the individual patient. The aim is to provide greater hemodynamic and respiratory stability, more stable depth of anesthesia, the ability to predict recovery and to administer a lower total dose of drug. Previous work in closed-loop control of intravenous anesthesia has focused on the titration of propofol in response to a depth of hypnosis (DOH) measure derived from the electroencephalogram (EEG).
The purpose of this pilot study is to evaluate iControl-RP, a system, which performs controlled delivery of both remifentanil and propofol infusions. iControl-RP allows either drug to be operated in any of 3 modes: closed-loop control based on feedback from an EEG measure supplied by NeuroSENSE (1); target-controlled infusion (TCI), based on previously-described pharmacokinetic (PK) and pharmacodynamic (PD) models; and conventional manual infusion, which require a weight-based dose setting.
A pilot two-phase study will be undertaken in a group of adult patients under the direct and immediate supervision of an experienced anesthesiologist. In Phase 1 (involving 50 study subjects), propofol will be administered in closed-loop mode and a remifentanil infusion will be administered based on a TCI. The data collected in this phase will be used to tune the controller parameters, which are initially based on previously published PKPD data. The controller performance will then be evaluated in phase 2 (involving 100 study subjects), in which both propofol and remifentanil will be administered in closed loop mode. In both phases, cases will be selected from those receiving propofol and remifentanil as anesthetic agents for routine surgical procedures.
The investigators aim to demonstrate that closed-loop control of anesthesia and analgesia based on EEG feedback is clinically feasible. This pilot study will help us take a significant step towards a controlled trial in which the clinical benefit of this method of closed-loop control of anesthesia can be assessed.
Detailed description
Purpose:
The purpose of this pilot study is to demonstrate that controlled delivery of remifentanil and propofol is clinically feasible and to collect a sample of clinical data to optimise the control functions. That is,
to demonstrate that the iControl remifentanil-propofol control system (iControl-RP) can be used to provide safe and effective administration of anesthesia (while maintaining the requirement for intervention by the anaesthesiologist when necessary) to collect a sample of clinical data that will allow the ECEM engineers to optimise the parameters of the iControl-RP control system
Justification:
Closed-loop control provides an opportunity to deliver anesthetic drugs at variable rate that is personalized to the individual patient. This suggests that it may provide greater hemodynamic and respiratory stability, more stable depth of anesthesia, the ability to predict recovery and to administer a lower total dose of drug.
Much development work is still required to mesh closed-loop control technology with anesthetic practice. The results of this initial study will feed into a subsequent larger study wherein the clinical, operational and economic benefits of closed-loop control of anesthesia will be submitted to a controlled trial.
Objectives:
The primary objective of this pilot study is to demonstrate the feasibility of closed-loop control of the delivery of both propofol and remifentanil using DOH feedback from the NeuroSENSE and show that it is a safe and effective mechanism for the administration of anesthesia and analgesia in adult patients undergoing routine elective surgical procedures. The secondary objective of this pilot study is to collect a sample of clinical data to optimise the tuning parameters for this system.
Research Method:
A pilot two-phase study will be undertaken in a group of adult patients under the direct and immediate supervision of an experienced anesthesiologist:
Phase 1: tuning controller parameters Propofol infusion will be closed-loop controlled; remifentanil will run as a target-controlled infusion (TCI); this system is comparable to the system evaluated in adult patients at the Hôpital Foch, Franc. The goal of this phase is to collect data to validate the mid-ranging controller design, which is based on population-based PKPD models.
Phase 2: evaluating controller performance The mid-ranging control system will be evaluated; both propofol and remifentanil infusion rates will be closed-loop controlled.
In both phases, cases will be selected from among patients who would be receiving propofol and remifentanil as the anesthetic agents for the planned procedure.
Research procedures will be similar in the two study phases. The anesthesiologist will closely monitor the patient as per routine practice and have the ability, at any time, to modify the anesthetic/analgesic drugs being administered. That is, he/she will be able to adjust the target DOH effect; adjust the target effect site concentration for remifentanil; immediately switch to manual control of either infusion; administer a bolus dose or immediately stop the infusion of either drug.
Investigational device iControl-RP has been developed for this study by the ECEM group at UBC headed by Prof. Dumont. iControl-RP is a control system developed for automatic closed-loop drug delivery in anesthesia. In this study remifentanil will be used as the fast actuator (control of analgesia) and propofol will be use as the slow actuator (control of hypnosis). Remifentanil is used to counteract disturbances in the measured DOH related to insufficient analgesia and propofol is used to maintain a stable baseline DOH. iControl-RP is connected to the NeuroSENSE, 2 infusion pumps for separately-controlled propofol and remifentanil administration, and the operating room (OR) patient monitor. It has a user interface, which displays the WAVCNS, infusion rates and effect site concentrations for both propofol and remifentanil. The user interface allows the anesthesiologist to set the target WAVCNS, to switch between modes of operation (manual, TCI, closed-loop) and set manual infusion rates or target effect-site concentrations for either drug, as required.
The system has been extensively tested in the laboratory for usability, reliability and repeatability. The vital signs collected from the OR patient monitor provide information for safety alerts.
Health Canada Investigational approval is being sought and will be received before commencement of study.
How the system works iControl-RP controls the infusion rates of a propofol infusion pump (Alaris TIVA) and a remifentanil infusion pump (Graseby 3400). The system allows either drug infusion to be operated in any of 3 modes: closed-loop control, which relies on WAVCNS feedback from the NeuroSENSE; TCI, which is based on PKPD models; and manual, which requires a weight-based dose setting (.e.g in mcg/kg/min).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| iControl-RP | Other | Device: iControl-RPiControl-RP is a system which performs controlled delivery of both remifentanil and propofol infusions. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 19 years of age or older
- ASA I-III
- Elective surgical procedures performed in the operating room at Royal Columbian Hospital requiring TIVA
- Ability to provide informed consent
Key exclusion criteria (8 listed)
- Contra-indications to the administration of propofol and/or remifentanil:
- propofol is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products; remifentanil is contraindicated in patients with known hypersensitivity to fentanyl analogs.
- Known or suspected neurological disease
- Known abnormality in any previous EEG examination
- Chronic opioid analgesic (more than 10 doses in previous one month) or other sedative drug therapy
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 |
|---|---|---|
| iControl-RP | Device | iControl-RP |
Primary outcome
Depth of Hypnosis (WAVcns)
Time frame: Continually assessed throughout anesthesia
Depth of hypnosis measurements will be used among other parameters to assess the feasibility of the system for delivery of propofol and remifentanil for anesthesia
1 secondary outcome
Time until induction complete (Tind)
Time frame: Beginning of anesthesia
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 24 Aug 2016.
- Derived from this study: PubMed 29210791West N, van Heusden K, Gorges M, Brodie S, Rollinson A, Petersen CL, Dumont GA, Ansermino JM, Merchant RN. Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System. Anesth Analg. 2018 Oct;127(4):883-894. doi: 10.1213/ANE.0000000000002663.
- UBC's Pediatric Anesthesia Research TeamLink provided by the sponsor.
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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.
Richard Merchant principal investigator
Royal Columbian Hospital and University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Anesthesia, run by Fraser Health 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 4 inclusion and 8 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 24 Aug 2016. 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.
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?
Depth of Hypnosis (WAVcns) (time frame: Continually assessed throughout anesthesia). 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 NCT01771263, 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 24 Aug 2016.