AnesthesiaTIVAlyNCT05199883
The TI.VA Algorithm: A First-in-Humans Test.
A study testing TI.VA algorithm: decision support system in people with Anesthesia, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation. TI.VA is a multiple inputs/multiple outputs algorithm. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anesthesia
- What is being tested?
- TI.VA algorithm: decision support system
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteItaly
- Study dates
- 1 Dec 2020to 31 Jan 2021
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
The inclusion criteria were: :
- age 18-65 years at the time of recruitment.
- candidates for curative surgery for breast cancer.
- American Society of Anaesthesiologists (ASA) status I/II.
The exclusion criteria were:
- ASA status > II.
- counter-indications for use of the drugs employed in this protocol.
- pregnancy or lactation.
- incapacity to understand the study explanation and sign the informed consent form.
These criteria were selected according to the risk mitigation strategy described in the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The TI.VA Algorithm: Vector Analysis Applied to a Decision-Making Matrix to Model the Reactive Control Strategy During General Anesthesia: a First-in-Humans Test.
The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.
TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix. The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the PAZ, the algorithm proposes an intervention on the hypnotic and/or opioid levels (algorithm outputs).
A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm.
Read the detailed description
The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.
TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix (DMM). The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the OAZ, the algorithm quantifies the inadequacy of anesthesia level through a vector connecting the patient's current position on the DMM to the central point identified by the coordinates BIS= 50 and MAP = 75mmHg. Thereafter, the analysis of the vector main components allows the generation of two coefficients that are used to set out a balanced intervention on the hypnotic and opioid levels (algorithm outputs).
A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm This is a prospective study involving a single cohort of patients without major comorbidity and candidate for minor superficial surgery. All patients received Propofol and Remifentanil administered by TCI systems as part of Total Intravenous Anaesthesia.
The algorithm was tested during maintenance of anesthesia defined as the period between skin incision and completion of surgical resection. In this step of the procedure, the titration strategy for anesthetic drug concentrations was suggested by TI.VA algorithm.
Data was collected automatically using dedicated software.
- Conditions
- Anesthesia
- Being tested
- TI.VA algorithm: decision support system
- Keywords
- open feedback control system, Balanced Anaesthesia, Total Intravenous Anaesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TI.VA algorithm: decision support systemOther
TI.VA algorithm uses BIS and MAP values as control variables to suggest the intervention on propofol and remifentanil levels.
| Study group | Role | What they receive |
|---|---|---|
| TI.VA group | Experimental | The titration of Propofol and Remifentanil levels will be guided by TI.VA algorithm in the time between skin incision and completion of surgical resection. Receives: Other: TI.VA algorithm: decision support system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
An adverse event is defined as any untoward medical occurrence in the study period. Intra-operative adverse events were reported using the institutional incident reporting system. Data was collected in the time between skin incision and the completion of surgical resection.
Measured: during the surgical procedure intervention
Secondary outcomes (2)
Stability of the Control Variables
To characterize the patient's repose to surgery, the TI.VA algorithm uses a Decision-Making Matrix drawn by crossing BIS (Min-max: 0-100, optimal range 40-60 ) and Mean Arterial Pressure (Min-max: 0-150mmHg. Optimal range 65-75mmHg). The Optimal anesthesia zone is defined as the area of the Decision-Making Matrix identify by the optimal range for the two control variables (BIS and MAP).
The stability of the control variables during anesthesia was quantified by the percentage of monitoring points registered in the Optimal Anaesthesia Zone during anesthesia.
A monitoring point is understood as a value of BIS and MAP recorded at the same time. The system records a monitoring point every 5 seconds.
Data was collected in the time between skin incision and the completion of surgical resection.
Measured: during the surgical procedure intervention
Performance Error analysis
The performance of the algorithm was assessed using the performance error (PE), median PE (MDPE), median absolute PE (MDAPE), and wobble according to the method of Performance Error.
Data was collected in the time between skin incision and the completion of surgical resection.
Measured: during the surgical procedure intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start1 Dec 2020
- Primary completion31 Jan 2021
- Study completion31 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective study involving a series of consecutive patients.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emiliano Tognoli, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Investigators
- Emiliano Tognoli, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199883
- Sponsor's protocol ID
- INT150/20
- Acronym
- TIVAly
- Status last verified
- Jan 2022
- First submitted
- 21 Oct 2021
- Last updated
- 3 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Publications
Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.
PubMed 21190458A.R. Absalom, MMRF Struys. Overview on Target Controlled Infusion and Total Intravenous Anaesthesia. 2Ed. Gent, Academia Press 2019.
Absalom AR, De Keyser R, Struys MM. Closed loop anesthesia: are we getting close to finding the holy grail? Anesth Analg. 2011 Mar;112(3):516-8. doi: 10.1213/ANE.0b013e318203f5ad. No abstract available.
PubMed 21350226Varvel JR, Donoho DL, Shafer SL. Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm. 1992 Feb;20(1):63-94. doi: 10.1007/BF01143186.
PubMed 1588504Tognoli E, Luigi M. Using the TI.VA algorithm to titrate the depth of general anaesthesia: a first-in-humans study. BJA Open. 2023 Jun 16;7:100203. doi: 10.1016/j.bjao.2023.100203. eCollection 2023 Sep.
PubMed 37638086
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The TI.VA Algorithm: Vector Analysis Applied to a Decision-Making Matrix to Model the Reactive Control Strategy During General Anesthesia: a First-in-Humans Test.
- ClinicalTrials.gov ID
- NCT05199883
- Acronym / sponsor ID
- TIVAly / INT150/20
- Conditions
- Anesthesia
- Keywords
- open feedback control system, Balanced Anaesthesia, Total Intravenous Anaesthesia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 31 Jan 2021 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 20 Jan 2022 (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 TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.
TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix. The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the PAZ, the algorithm proposes an intervention on the hypnotic and/or opioid levels (algorithm outputs).
A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm.
Detailed description
The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.
TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix (DMM). The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the OAZ, the algorithm quantifies the inadequacy of anesthesia level through a vector connecting the patient's current position on the DMM to the central point identified by the coordinates BIS= 50 and MAP = 75mmHg. Thereafter, the analysis of the vector main components allows the generation of two coefficients that are used to set out a balanced intervention on the hypnotic and opioid levels (algorithm outputs).
A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm This is a prospective study involving a single cohort of patients without major comorbidity and candidate for minor superficial surgery. All patients received Propofol and Remifentanil administered by TCI systems as part of Total Intravenous Anaesthesia.
The algorithm was tested during maintenance of anesthesia defined as the period between skin incision and completion of surgical resection. In this step of the procedure, the titration strategy for anesthetic drug concentrations was suggested by TI.VA algorithm.
Data was collected automatically using dedicated software.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective study involving a series of consecutive patients.
| Arm | Type | Receives |
|---|---|---|
| TI.VA group | Experimental | Other: TI.VA algorithm: decision support systemThe titration of Propofol and Remifentanil levels will be guided by TI.VA algorithm in the time between skin incision and completion of surgical resection. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| TI.VA algorithm: decision support systemTI.VA algorithm uses BIS and MAP values as control variables to suggest the intervention on propofol and remifentanil levels. | Other | TI.VA group |
Primary outcome
Adverse Events
Time frame: during the surgical procedure intervention
An adverse event is defined as any untoward medical occurrence in the study period. Intra-operative adverse events were reported using the institutional incident reporting system. Data was collected in the time between skin incision and the completion of surgical resection.
2 secondary outcomes
Stability of the Control Variables
Time frame: during the surgical procedure intervention
Performance Error analysis
Time frame: during the surgical procedure intervention
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 3 Feb 2022.
- Background: PubMed 21190458Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.
- BackgroundA.R. Absalom, MMRF Struys. Overview on Target Controlled Infusion and Total Intravenous Anaesthesia. 2Ed. Gent, Academia Press 2019.
- Background: PubMed 21350226Absalom AR, De Keyser R, Struys MM. Closed loop anesthesia: are we getting close to finding the holy grail? Anesth Analg. 2011 Mar;112(3):516-8. doi: 10.1213/ANE.0b013e318203f5ad. No abstract available.
- Background: PubMed 1588504Varvel JR, Donoho DL, Shafer SL. Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm. 1992 Feb;20(1):63-94. doi: 10.1007/BF01143186.
- Derived from this study: PubMed 37638086Tognoli E, Luigi M. Using the TI.VA algorithm to titrate the depth of general anaesthesia: a first-in-humans study. BJA Open. 2023 Jun 16;7:100203. doi: 10.1016/j.bjao.2023.100203. eCollection 2023 Sep.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
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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.
Emiliano Tognoli, MD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TI.VA algorithm: decision support system in people with Anesthesia, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 3 Feb 2022. 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 Italy. 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?
Adverse Events (time frame: during the surgical procedure intervention). 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 NCT05199883, which also lists 5 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 3 Feb 2022.