AnesthesiaHUAPQNCT03704285
Development of pk/pd Model of Propofol in Patients With Severe Burns
An observational study of Anesthesia and Burned, run by Victor Contreras, MSN at 1 site in Chile.
Trial summary
Burn injuries are a prevalent problem. Actually, in Chile the Ministry of Health has recorded 6435 hospital burns and has reported 569 deaths from this cause. The specific mortality rate for burning in Chile was 4.5 per 100,000 inhabitants per year. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anesthesia, Burned, Operative Wound
- What is being tested?
- Propofol and BIS
- Type of treatment
- Injection or infusion, Medical device
- How many people
- 15 participants
- Where
- 1 siteChile
- Study dates
- 29 Sep 2018to 30 Dec 2021
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults with Major burns
Who may be able to join
- Severe burns with life risk that require treatment in Burn Units and / or Critical Patient Units.
- In spontaneous ventilation
- SAS 4
Who cannot join
- Electric burns
- ASA IV o V
- Inability to install BIS
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Development of Pharmacokinetic / Pharmacodynamic (pk/pd) Model of Propofol in Patients With Severe Burns
Burn injuries are a prevalent problem. Actually, in Chile the Ministry of Health has recorded 6435 hospital burns and has reported 569 deaths from this cause. The specific mortality rate for burning in Chile was 4.5 per 100,000 inhabitants per year. Survival in extensive burns has progressively improved, thanks to advances in understanding the pathophysiology of the burn and its more aggressive treatment. This requires effective prehospital treatment, transportation, resuscitation, support of vital functions and repair of the skin cover.
Much of the procedures performed in large burns require general anesthesia. Being Total Intravenous Anesthesia (TIVA) with propofol an alternative that would have advantages over inhalational anesthesia, as a decrease in postoperative nausea and vomiting and produce less environmental pollution 3 and the antihyperalgesic effect of propofol. Within TIVA - Target Control Infusion (TCI) - uses infusion systems that incorporate PK-PD models for predict the dose of drug required to reach a certain concentration in the target organ.
Read more
The formulation of a PK model that considers the variables of this group of patients, such as: degree of injury, inflammatory state and compromised body surface; associated with general variables such as: age, weight and nutrition, it would allow to reduce the predictive error in this population, thus improving the dosing of these patients when using TCI.
Given the lack evidence on the PK-PD of propofol is this group of patients burned, has led to raise the development of this study that seeks to develop a PK-PD model that fits them.
Read the detailed description
Patients will be invited to participate before surgery, the inclusion criteria will be revised and the informed consent will be signed.
In the operating room will be recorded demographic data and relevant background such as: Age, Weight, Size, BMI, Lean Mass, Fat Mass and Total body water among others.
Afterwards, in the operating room, the patient will be monitored regularly: ECG (DII) if feasible and pulse oximetry. An arterial catheter will be installed for monitoring and taking blood samples during the intraoperative period.
In addition, the EEG will be monitored through a frontal electroencephalographic monitoring (BIS) system; that will be recorded throughout the surgery.
The anesthetic induction will be with propofol and remifentanil. The propofol will be administered using an initial bolus of 1-2 mg / kg according to the criteria of the anesthetist and then a continuous infusion of 10 mg / kg / hr that will be adjusted adjusted to maintain a BIS between 40 and 60.
Plasma samples of propofol: arterial samples of 3-4 ml will be taken at 2, 5, 10, 30, 60 and/or 120 min after beginning the administration of propofol. Subsequently samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping the infusion of propofol. The samples will be centrifuged and stored at -20 ° C until analysis by HPLC.
- Conditions
- Anesthesia, Burned, Operative Wound
- Being tested
- Propofol, BIS
- Keywords
- anesthesia, burned, TIVA, propofol
- Medical subject headings
- Burns, Surgical Wound
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called Propofol Intravenous dose
Patients undergoing general anesthesia using target controlled infusion of propofol. Initial bolus of 1-2 mg/kg and then a continuous infusion of 10 mg/kg/hr that will be adjusted adjusted to maintain a BIS between 40 and 60.
BISDevice
Also called General anesthetic
GeneralAnesthesia maintenance with propofol+remifentanil guided by BIS monitoring.
| Study group | Role | What they receive |
|---|---|---|
| Propofol | Severe burn adult under general anesthesia with propofol + remifentanil evaluation of propofol effect using BIS Receives: Drug: Propofol; Device: BIS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Propofol plasmatic levels Measured by high pressure liquid chromatography
Propofol total dose. 2, 5, 10, 30, 60 and 120 min after induction with propofol. Subsequently, samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping infusion of propofol.
Measured: From start of propofol infusion to 12 hrs after stopped infusion of propofol.
Secondary outcomes (4)
Hemodynamics
Arterial pressure (mmHg)
Measured: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Heart Rate
Heart rate (bpm)
Measured: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Pulse oximetry
% oximetry saturation
Measured: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
BIS
Depth of anesthesia will be recorded with BIS monitor. From 60 - 40
Measured: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2018
- Study start29 Sep 2018
- Primary completion30 Dec 2021
- Study completion30 Dec 2021
Why it stopped: Outbreak COVID 19
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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Victor Contreras, MSN
- Sponsor type
- University, hospital or other
- Collaborators
- Pontificia Universidad Catolica de Chile
- Responsible party
- Sponsor-investigator, Victor Contreras, MSN, Pontificia Universidad Catolica de Chile
- Investigators
- Luis I Cortinez, MD, Study director, Pontificia Universidad Catolica de Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03704285
- Sponsor's protocol ID
- 171215006
- Acronym
- HUAPQ
- Status last verified
- Mar 2022
- First submitted
- 3 Oct 2018
- Last updated
- 8 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Shin SW, Cho AR, Lee HJ, Kim HJ, Byeon GJ, Yoon JW, Kim KH, Kwon JY. Maintenance anaesthetics during remifentanil-based anaesthesia might affect postoperative pain control after breast cancer surgery. Br J Anaesth. 2010 Nov;105(5):661-7. doi: 10.1093/bja/aeq257. Epub 2010 Sep 28.
PubMed 20876698Cortinez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sepulveda P, Ibacache M, Solari S. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth Analg. 2014 Aug;119(2):302-310. doi: 10.1213/ANE.0000000000000317.
PubMed 24977639Cortinez LI, Anderson BJ, Penna A, Olivares L, Munoz HR, Holford NH, Struys MM, Sepulveda P. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth. 2010 Oct;105(4):448-56. doi: 10.1093/bja/aeq195. Epub 2010 Aug 14.
PubMed 20710020Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12.
PubMed 29661412Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramirez C, Oliveros AM, Ibacache M. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018 May;120(5):969-977. doi: 10.1016/j.bja.2018.01.040. Epub 2018 Mar 28.
PubMed 29661414
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Pharmacokinetic / Pharmacodynamic (pk/pd) Model of Propofol in Patients With Severe Burns
- ClinicalTrials.gov ID
- NCT03704285
- Acronym / sponsor ID
- HUAPQ / 171215006
- Conditions
- Anesthesia, Burned, Operative Wound
- Keywords
- anesthesia, burned, TIVA, propofol
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Outbreak COVID 19
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Victor Contreras, MSNUniversity, hospital or other
- Collaborators
- Pontificia Universidad Catolica de Chile
- Study start
- 29 Sep 2018 (actual)
- Primary completion
- 30 Dec 2021 (actual)
- Study completion
- 30 Dec 2021 (actual)
- First posted
- 12 Oct 2018 (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.
Burn injuries are a prevalent problem. Actually, in Chile the Ministry of Health has recorded 6435 hospital burns and has reported 569 deaths from this cause. The specific mortality rate for burning in Chile was 4.5 per 100,000 inhabitants per year. Survival in extensive burns has progressively improved, thanks to advances in understanding the pathophysiology of the burn and its more aggressive treatment. This requires effective prehospital treatment, transportation, resuscitation, support of vital functions and repair of the skin cover.
Much of the procedures performed in large burns require general anesthesia. Being Total Intravenous Anesthesia (TIVA) with propofol an alternative that would have advantages over inhalational anesthesia, as a decrease in postoperative nausea and vomiting and produce less environmental pollution 3 and the antihyperalgesic effect of propofol. Within TIVA - Target Control Infusion (TCI) - uses infusion systems that incorporate PK-PD models for predict the dose of drug required to reach a certain concentration in the target organ.
The formulation of a PK model that considers the variables of this group of patients, such as: degree of injury, inflammatory state and compromised body surface; associated with general variables such as: age, weight and nutrition, it would allow to reduce the predictive error in this population, thus improving the dosing of these patients when using TCI.
Given the lack evidence on the PK-PD of propofol is this group of patients burned, has led to raise the development of this study that seeks to develop a PK-PD model that fits them.
Detailed description
Patients will be invited to participate before surgery, the inclusion criteria will be revised and the informed consent will be signed.
In the operating room will be recorded demographic data and relevant background such as: Age, Weight, Size, BMI, Lean Mass, Fat Mass and Total body water among others.
Afterwards, in the operating room, the patient will be monitored regularly: ECG (DII) if feasible and pulse oximetry. An arterial catheter will be installed for monitoring and taking blood samples during the intraoperative period.
In addition, the EEG will be monitored through a frontal electroencephalographic monitoring (BIS) system; that will be recorded throughout the surgery.
The anesthetic induction will be with propofol and remifentanil. The propofol will be administered using an initial bolus of 1-2 mg / kg according to the criteria of the anesthetist and then a continuous infusion of 10 mg / kg / hr that will be adjusted adjusted to maintain a BIS between 40 and 60.
Plasma samples of propofol: arterial samples of 3-4 ml will be taken at 2, 5, 10, 30, 60 and/or 120 min after beginning the administration of propofol. Subsequently samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping the infusion of propofol. The samples will be centrifuged and stored at -20 ° C until analysis by HPLC.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Propofol | – | Drug: Propofol, Device: BISSevere burn adult under general anesthesia with propofol + remifentanil evaluation of propofol effect using BIS |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with Major burns
Key inclusion criteria (3 listed)
- Severe burns with life risk that require treatment in Burn Units and / or Critical Patient Units.
- In spontaneous ventilation
- SAS 4
Key exclusion criteria (3 listed)
- Electric burns
- ASA IV o V
- Inability to install 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 |
|---|---|---|
| PropofolAlso: Propofol Intravenous dosePatients undergoing general anesthesia using target controlled infusion of propofol. Initial bolus of 1-2 mg/kg and then a continuous infusion of 10 mg/kg/hr that will be adjusted adjusted to maintain a BIS between 40 and 60. | Drug | Propofol |
| BISAlso: General anestheticGeneralAnesthesia maintenance with propofol+remifentanil guided by BIS monitoring. | Device | Propofol |
Primary outcome
Propofol plasmatic levels Measured by high pressure liquid chromatography
Time frame: From start of propofol infusion to 12 hrs after stopped infusion of propofol.
Propofol total dose. 2, 5, 10, 30, 60 and 120 min after induction with propofol. Subsequently, samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping infusion of propofol.
4 secondary outcomes
Hemodynamics
Time frame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Heart Rate
Time frame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Pulse oximetry
Time frame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
BIS
Time frame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Results and safety
The study was stopped early (reason given: Outbreak COVID 19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2022.
- Background: PubMed 20876698Shin SW, Cho AR, Lee HJ, Kim HJ, Byeon GJ, Yoon JW, Kim KH, Kwon JY. Maintenance anaesthetics during remifentanil-based anaesthesia might affect postoperative pain control after breast cancer surgery. Br J Anaesth. 2010 Nov;105(5):661-7. doi: 10.1093/bja/aeq257. Epub 2010 Sep 28.
- Background: PubMed 24977639Cortinez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sepulveda P, Ibacache M, Solari S. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth Analg. 2014 Aug;119(2):302-310. doi: 10.1213/ANE.0000000000000317.
- Background: PubMed 20710020Cortinez LI, Anderson BJ, Penna A, Olivares L, Munoz HR, Holford NH, Struys MM, Sepulveda P. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth. 2010 Oct;105(4):448-56. doi: 10.1093/bja/aeq195. Epub 2010 Aug 14.
- Background: PubMed 29661412Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12.
- Background: PubMed 29661414Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramirez C, Oliveros AM, Ibacache M. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018 May;120(5):969-977. doi: 10.1016/j.bja.2018.01.040. Epub 2018 Mar 28.
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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.
Luis I Cortinez, MD study director
Pontificia Universidad Catolica de Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anesthesia and Burned, run by Victor Contreras, MSN at 1 site in Chile.
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 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: stopped early, as of the sponsor's last update on 8 Mar 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 Chile. 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 was stopped early (reason given: Outbreak COVID 19). 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?
Propofol plasmatic levels Measured by high pressure liquid chromatography (time frame: From start of propofol infusion to 12 hrs after stopped infusion of propofol.). 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 NCT03704285, 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 8 Mar 2022.