General AnesthesiaNCT03073408
Design of a Closed-loop Controller Based on the Bispectral Index (BIS) Effectiveness of the Smith Predictor
A study testing Propofol in people with General Anesthesia, run by José Antonio Reboso Morales at 1 site in Spain.
Trial summary
The action of anesthetics such as propofol is not immediate after intravenous administration. Delay in pharmacodynamic effect of intravenous drugs is a commonly observed phenomenon in total intravenous anesthesia (TIVA). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- General Anesthesia
- What is being tested?
- Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 6 Mar 2017to 15 Sep 2017
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide informed consent
- 18 years of age or older
- Classification of the American Society of Anesthesiologists (ASA) as I or II
- Elective surgical procedures requiring general anesthesia with an estimated duration > 30 minutes
Who cannot join
- Pregnant women,
- Patients with neurological or psychiatric disorders
- Patients taking any medication known to influence the EEG and subsequently the BIS
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320
About this study
Official title: Design of a Closed-loop Controller for the Administration of Propofol Based on the Bispectral Index (BIS). Effectiveness of the Smith Predictor and Comparison With Manual Control
The action of anesthetics such as propofol is not immediate after intravenous administration. Delay in pharmacodynamic effect of intravenous drugs is a commonly observed phenomenon in total intravenous anesthesia (TIVA). On the other hand, the measure of the clinical effect of propofol by EEG processed monitors like the bispectral index (BIS) also requires some processing time for the analysis of the recorded signal. Thus, the resulting BIS value provided by the monitor is affected by a delay. When a BIS based controller is used, the propofol infusion rates are defined using information of the BIS signal available. The delay in the BIS signal is an important issue as it can affect the performance of the controller. There are scarce contributions to address the delay in automatic administration of anesthesia.
Our proposal to deal with the dead time in the control action of the hypnotic component of anesthesia is a proportional-integral (PI) algorithm with a Smith predictor. The aim of this study is to evaluate and compare the feasibility and effectiveness of a closed-loop control using the Smith predictor versus manual control for propofol administration guided by the bispectral index (BIS) in adults patients. The objective is to show that a closed loop control can be a useful tool to provide safe and effective intravenous anesthesia and that the use of specific controller for delay rejection is a reliable strategy.
Read the detailed description
Modern medicine is focused on individualized treatment, including a personalized anesthesia administration. This implies to maintain the patient hypnotic state as closer as possible to a set target. TIVA with propofol and remifentanil has increased in popularity in recent years. Automatic systems can free the anesthesiologist of repetitive tasks. So, closed loop administration has been proposed to adjust propofol infusion rate without anesthesiologist intervention apart from supervising the procedure. A desired target of BIS is chosen by the clinician and feedback from the BIS monitor is used to adjust the rate of drug delivery continuously.
Closed loop control offers the opportunity of adjust the administration of anesthetics in an individualized way. It is also expected to overcome the individual pharmacokinetic and pharmacodynamic variability and to show a better adaptation to different levels of surgical stimulation. Closed loop control of propofol administration provides a greater stability in the level of hypnosis with a lower total dose of drug administered. Therefore, the recovery after anesthesia can be shorter. This can promote a better quality anesthetic care.
Previous studies with a PI controller showed in some patients a tendency to oscillate around a target value. This can be originated by the delay present in the system. One of the most known strategies in engineering to face the delay in closed loop is the Smith predictor. The purpose of this study is to evaluate and compare the feasibility and efficacy of a closed-loop control with a PI plus a Smith predictor algorithm versus manual control for propofol administration guided by the bispectral index (BIS) in adults patients.
Two groups of 25 adult patients scheduled for gynecological, urologic or abdominal surgery with an estimated duration > 30 minutes will be enrolled and randomized to one of the 2 groups. In the Manual control group (MC), the propofol infusion rate will be adjusted at the discretion of the anesthesiologist. In the PI+Smith group, propofol will be administered automatically by the closed-loop anesthesia system. The controller calculated automatically the error (target BIS - actual BIS) every 5 s and governed the infusion pump adapting the rate of propofol. The goal in both groups is to maintain BIS between 40 and 60 during maintenance phase of anesthesia. This is the recommended range of BIS for an adequate level of hypnosis during general anesthesia. Remifentanil will be infused for analgesia with the objective of to avoid an inadequate level of analgesia that could affect the stability of BIS signal.
- Conditions
- General Anesthesia
- Being tested
- Propofol
- Keywords
- Propofol, Bispectral index (BIS), Closed loop
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Closed loop control for propofol administration guided by the BIS.
PropofolDrug
Manual control group: Propofol administration adjusted manually.
| Study group | Role | What they receive |
|---|---|---|
| 1: Manual control group | Active comparator | The propofol infusion rate is adjusted manually in a pump by the investigator to maintain BIS between 40 and 60. For this titration it is necessary continuous monitoring, clinical experience, and pharmacokinetic/pharmacodynamic knowledge. Receives: Drug: Propofol |
| 2: PI +Smith group | Experimental | The closed loop control automatically adjust propofol infusion rate guided by the feedback of the real value of BIS. The automatic system has to achieve a target BIS of 50 and maintain it between 40 and 60. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the performance of the 2 groups with the global score (GS).
Global score is a calculated parameter which gives an idea of the overall performance of a closed-loop system. It is calculated as the sum of MDAPE and wobble divided by the fraction of time BIS was within ±10 of the target. The target BIS chosen will be 50. The GS is calculated according the formula:
GS = (MDAPE + wobble)/ % of time with BIS between 40 and 60
Measured: During anesthesia maintenance, approximately 9 hours
Secondary outcomes (7)
The percentage of time with BIS values within +/10 % of target BIS.
Adequate depth of anaesthesia during surgical interventions
Measured: During anesthesia maintenance, approximately 9 hours
MDPE (median performance error)
The difference between the observed and target value of BIS.
Measured: During anesthesia maintenance, approximately 9 hours
MDAPE (median absolute performance error):
The median of the absolute values of performance errors.
Measured: During anesthesia maintenance, approximately 9 hours
Wobble
The median of the difference between individual PE and the MDPE for each participant, it measures the intra-individual variability of PE.
Measured: During anesthesia maintenance, approximately 9 hours
Time to eyes opening
Time from discontinuation of the propofol and remifentanil infusions until the patient is able to open his eyes on command.
Measured: 30 minutes after the end of the anesthesia
Time to tracheal extubation:
Time from discontinuation of propofol infusion until endotracheal tube removal.
Measured: 30 minutes after the end of the anesthesia
Total consumption of propofol and remifentanil during anesthesia maintenance
Propofol administered
Measured: During anesthesia maintenance, approximately 9 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2017
- Study start6 Mar 2017 (estimated)
- Primary completion15 Sep 2017 (estimated)
- Study completion15 Sep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for General 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- José Antonio Reboso Morales
- Sponsor type
- University, hospital or other
- Collaborators
- University of La Laguna
- Responsible party
- Sponsor-investigator, José Antonio Reboso Morales, Hospital Universitario de Canarias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03073408
- Sponsor's protocol ID
- 2017
- Status last verified
- Mar 2017
- First submitted
- 24 Feb 2017
- Last updated
- 8 Mar 2017
- 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 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Design of a Closed-loop Controller for the Administration of Propofol Based on the Bispectral Index (BIS). Effectiveness of the Smith Predictor and Comparison With Manual Control
- ClinicalTrials.gov ID
- NCT03073408
- Acronym / sponsor ID
- 2017
- Conditions
- General Anesthesia
- Keywords
- Propofol, Bispectral index (BIS), Closed loop
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- José Antonio Reboso MoralesUniversity, hospital or other
- Collaborators
- University of La Laguna
- Study start
- 6 Mar 2017 (estimated)
- Primary completion
- 15 Sep 2017 (estimated)
- Study completion
- 15 Sep 2017 (estimated)
- First posted
- 8 Mar 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.
The action of anesthetics such as propofol is not immediate after intravenous administration. Delay in pharmacodynamic effect of intravenous drugs is a commonly observed phenomenon in total intravenous anesthesia (TIVA). On the other hand, the measure of the clinical effect of propofol by EEG processed monitors like the bispectral index (BIS) also requires some processing time for the analysis of the recorded signal. Thus, the resulting BIS value provided by the monitor is affected by a delay. When a BIS based controller is used, the propofol infusion rates are defined using information of the BIS signal available. The delay in the BIS signal is an important issue as it can affect the performance of the controller. There are scarce contributions to address the delay in automatic administration of anesthesia.
Our proposal to deal with the dead time in the control action of the hypnotic component of anesthesia is a proportional-integral (PI) algorithm with a Smith predictor. The aim of this study is to evaluate and compare the feasibility and effectiveness of a closed-loop control using the Smith predictor versus manual control for propofol administration guided by the bispectral index (BIS) in adults patients. The objective is to show that a closed loop control can be a useful tool to provide safe and effective intravenous anesthesia and that the use of specific controller for delay rejection is a reliable strategy.
Detailed description
Modern medicine is focused on individualized treatment, including a personalized anesthesia administration. This implies to maintain the patient hypnotic state as closer as possible to a set target. TIVA with propofol and remifentanil has increased in popularity in recent years. Automatic systems can free the anesthesiologist of repetitive tasks. So, closed loop administration has been proposed to adjust propofol infusion rate without anesthesiologist intervention apart from supervising the procedure. A desired target of BIS is chosen by the clinician and feedback from the BIS monitor is used to adjust the rate of drug delivery continuously.
Closed loop control offers the opportunity of adjust the administration of anesthetics in an individualized way. It is also expected to overcome the individual pharmacokinetic and pharmacodynamic variability and to show a better adaptation to different levels of surgical stimulation. Closed loop control of propofol administration provides a greater stability in the level of hypnosis with a lower total dose of drug administered. Therefore, the recovery after anesthesia can be shorter. This can promote a better quality anesthetic care.
Previous studies with a PI controller showed in some patients a tendency to oscillate around a target value. This can be originated by the delay present in the system. One of the most known strategies in engineering to face the delay in closed loop is the Smith predictor. The purpose of this study is to evaluate and compare the feasibility and efficacy of a closed-loop control with a PI plus a Smith predictor algorithm versus manual control for propofol administration guided by the bispectral index (BIS) in adults patients.
Two groups of 25 adult patients scheduled for gynecological, urologic or abdominal surgery with an estimated duration > 30 minutes will be enrolled and randomized to one of the 2 groups. In the Manual control group (MC), the propofol infusion rate will be adjusted at the discretion of the anesthesiologist. In the PI+Smith group, propofol will be administered automatically by the closed-loop anesthesia system. The controller calculated automatically the error (target BIS - actual BIS) every 5 s and governed the infusion pump adapting the rate of propofol. The goal in both groups is to maintain BIS between 40 and 60 during maintenance phase of anesthesia. This is the recommended range of BIS for an adequate level of hypnosis during general anesthesia. Remifentanil will be infused for analgesia with the objective of to avoid an inadequate level of analgesia that could affect the stability of BIS signal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| 1: Manual control group | Active comparator | Drug: PropofolThe propofol infusion rate is adjusted manually in a pump by the investigator to maintain BIS between 40 and 60. For this titration it is necessary continuous monitoring, clinical experience, and pharmacokinetic/pharmacodynamic knowledge. |
| 2: PI +Smith group | Experimental | Drug: PropofolThe closed loop control automatically adjust propofol infusion rate guided by the feedback of the real value of BIS. The automatic system has to achieve a target BIS of 50 and maintain it between 40 and 60. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Ability to provide informed consent
- 18 years of age or older
- Classification of the American Society of Anesthesiologists (ASA) as I or II
- Elective surgical procedures requiring general anesthesia with an estimated duration > 30 minutes
Key exclusion criteria (3 listed)
- Pregnant women,
- Patients with neurological or psychiatric disorders
- Patients taking any medication known to influence the EEG and subsequently the BIS
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 |
|---|---|---|
| PropofolClosed loop control for propofol administration guided by the BIS. | Drug | 2: PI +Smith group |
| PropofolManual control group: Propofol administration adjusted manually. | Drug | 1: Manual control group |
Primary outcome
Evaluation of the performance of the 2 groups with the global score (GS).
Time frame: During anesthesia maintenance, approximately 9 hours
Global score is a calculated parameter which gives an idea of the overall performance of a closed-loop system. It is calculated as the sum of MDAPE and wobble divided by the fraction of time BIS was within ±10 of the target. The target BIS chosen will be 50. The GS is calculated according the formula: GS = (MDAPE + wobble)/ % of time with BIS between 40 and 60
7 secondary outcomes
The percentage of time with BIS values within +/10 % of target BIS.
Time frame: During anesthesia maintenance, approximately 9 hours
MDPE (median performance error)
Time frame: During anesthesia maintenance, approximately 9 hours
MDAPE (median absolute performance error):
Time frame: During anesthesia maintenance, approximately 9 hours
Wobble
Time frame: During anesthesia maintenance, approximately 9 hours
Time to eyes opening
Time frame: 30 minutes after the end of the anesthesia
Time to tracheal extubation:
Time frame: 30 minutes after the end of the anesthesia
Total consumption of propofol and remifentanil during anesthesia maintenance
Time frame: During anesthesia maintenance, approximately 9 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2017.
- 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 study testing Propofol in people with General Anesthesia, run by José Antonio Reboso Morales at 1 site in Spain.
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 3 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 8 Mar 2017. 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 Spain. 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?
Results are not available in the source record.
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?
Evaluation of the performance of the 2 groups with the global score (GS). (time frame: During anesthesia maintenance, approximately 9 hours). 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 8 Mar 2017.