Ischemia Reperfusion InjuryNCT03772054
Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.
A study testing Sevoflurane and Propofol in people with Ischemia Reperfusion Injury, run by University of Chile at 1 site in Chile.
Trial summary
Endothelial damage has been reported after ischemia-reperfusion events. This can be characterized by measurements of glycocalyx and endothelial components that are released to blood after the insult. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Ischemia Reperfusion Injury
- What is being tested?
- Sevoflurane and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteChile
- Study dates
- 20 Dec 2018to 11 Dec 2019
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- American Society of Anesthesiologists Classification (ASA Class) I and II
- Elective knee ligament surgery
- Use of a femoral tourniquet
Who cannot join
- Allergies to egg or soya
- Previous history of critical events during surgery and perioperative period
- Patients at risk of hyperthermia malignant
- Patients with 3 or more predictor of difficult airway management
Trial locations and contacts
1 site in 1 country.
Chile1 site
Hospital Clínico de la Universidad de Chile
Independencia, Santiago Metropolitan, 8380456
About this study
Official title: Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled Trial
Endothelial damage has been reported after ischemia-reperfusion events. This can be characterized by measurements of glycocalyx and endothelial components that are released to blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state after the tourniquet is released. This research aims to compare the effect of sevoflurane and propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical scenario.
Read the detailed description
To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal anesthesia.
After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of the study. All patients will enter the operating room and after standard ASA monitorization and placement of an intravenous line (IV), a spinal anesthesia will be performed under midazolam sedation. After analgesia and motor block establishment, an intravenous or inhalation hypnosis induction will be performed (according to the study arm allocation). The airway will be secured by a laryngeal mask placement and the surgery will be started. A femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will be taken in five different moments to follow concentration changes before and after the IR insult. Fluid and drugs administration will be standardized.
Venous blood samples will be collected at the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured by a researcher blinded to patient allocation using commercial available Elisa kits. The concentration of each biomarker at each sample time will be compared.
A sample size calculation was performed based on a few clinical reports to detect a 25% reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of 0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a two-sides test analysis.
- Conditions
- Ischemia Reperfusion Injury
- Being tested
- Sevoflurane, Propofol
- Keywords
- Syndecan-1, Heparan sulfate, Thrombomodulin, Ischemia Reperfusion, Anesthesia
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevofluraneDrug
Inhalation anesthetic agent
PropofolDrug
Intravenous anesthetic agent
| Study group | Role | What they receive |
|---|---|---|
| Propofol | Active comparator | After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery. Receives: Drug: Propofol |
| Sevoflurane | Experimental | After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery. Receives: Drug: Sevoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Syndecan-1 levels
Differences in the concentration of syndecan-1 in blood serum during and after surgery
Measured: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Secondary outcomes (2)
Heparan sulfate levels
Differences in the concentration of heparan sulfate in blood serum during and after surgery
Measured: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Thrombomodulin
Differences in the concentration of thrombomodulin in blood serum during and after surgery
Measured: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2018
- Study start20 Dec 2018
- Primary completion11 Dec 2019
- Study completion11 Dec 2019
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 Ischemia Reperfusion InjuryStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felipe Andrés Maldonado Caniulao, University of Chile
- Investigators
- Felipe Maldonado, M.D., M.Sc., Principal investigator, Hospital Clìnico de la Universidad de Chile.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03772054
- Sponsor's protocol ID
- 903/17
- Status last verified
- Dec 2019
- First submitted
- 9 Dec 2018
- Last updated
- 12 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maldonado F, Morales D, Gutierrez R, Barahona M, Cerda O, Caceres M. Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery. BMC Anesthesiol. 2020 May 20;20(1):121. doi: 10.1186/s12871-020-01030-w.
PubMed 32434495
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03772054
- Acronym / sponsor ID
- 903/17
- Conditions
- Ischemia Reperfusion Injury
- Keywords
- Syndecan-1, Heparan sulfate, Thrombomodulin, Ischemia Reperfusion, Anesthesia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Study start
- 20 Dec 2018 (actual)
- Primary completion
- 11 Dec 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 11 Dec 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.
Endothelial damage has been reported after ischemia-reperfusion events. This can be characterized by measurements of glycocalyx and endothelial components that are released to blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state after the tourniquet is released. This research aims to compare the effect of sevoflurane and propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical scenario.
Detailed description
To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal anesthesia.
After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of the study. All patients will enter the operating room and after standard ASA monitorization and placement of an intravenous line (IV), a spinal anesthesia will be performed under midazolam sedation. After analgesia and motor block establishment, an intravenous or inhalation hypnosis induction will be performed (according to the study arm allocation). The airway will be secured by a laryngeal mask placement and the surgery will be started. A femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will be taken in five different moments to follow concentration changes before and after the IR insult. Fluid and drugs administration will be standardized.
Venous blood samples will be collected at the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured by a researcher blinded to patient allocation using commercial available Elisa kits. The concentration of each biomarker at each sample time will be compared.
A sample size calculation was performed based on a few clinical reports to detect a 25% reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of 0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a two-sides test analysis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propofol | Active comparator | Drug: PropofolAfter spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery. |
| Sevoflurane | Experimental | Drug: SevofluraneAfter spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- American Society of Anesthesiologists Classification (ASA Class) I and II
- Elective knee ligament surgery
- Use of a femoral tourniquet
Key exclusion criteria (4 listed)
- Allergies to egg or soya
- Previous history of critical events during surgery and perioperative period
- Patients at risk of hyperthermia malignant
- Patients with 3 or more predictor of difficult airway management
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 |
|---|---|---|
| SevofluraneInhalation anesthetic agent | Drug | Sevoflurane |
| PropofolIntravenous anesthetic agent | Drug | Propofol |
Primary outcome
Syndecan-1 levels
Time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Differences in the concentration of syndecan-1 in blood serum during and after surgery
2 secondary outcomes
Heparan sulfate levels
Time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Thrombomodulin
Time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
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 12 Dec 2019.
- Derived from this study: PubMed 32434495Maldonado F, Morales D, Gutierrez R, Barahona M, Cerda O, Caceres M. Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery. BMC Anesthesiol. 2020 May 20;20(1):121. doi: 10.1186/s12871-020-01030-w.
- 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.
Felipe Maldonado, M.D., M.Sc. principal investigator
Hospital Clìnico de la Universidad de Chile.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sevoflurane and Propofol in people with Ischemia Reperfusion Injury, run by University of Chile 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 4 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 12 Dec 2019. 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 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?
Syndecan-1 levels (time frame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR). 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 NCT03772054, 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 12 Dec 2019.