Brain InjuryPhase 3IMLPBIAVRNCT02697786
Neuromonitoring in Patients During Aortic Valve Replacement
A Phase 3 study testing Transcranial doppler in people with Brain Injury, run by Marija Bozhinovska at 1 site in Slovenia.
Trial summary
Postoperative brain damage and neuropsychological disorders have been observed in 30 - 80 % of patients after heart surgery with the use of cardiopulmonary bypass (CPB).They can persist up to a year after cardiac surgery and are associated with increased hospital mortality and prolonged intrahospital stay. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Brain Injury
- What is being tested?
- Transcranial doppler
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSlovenia
- Study dates
- Jan 2016to Apr 2018
- Phase
- Phase 3
- 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
- Isolated aortic valve stenosis as well as asymptomatic patients with depressed systolic function
- Symptomatic patients with normal or depressed left ventricular function
- Patients with American Society of Anesthesiologist (ASA) physical status classification 2 or 3
Who cannot join
- History of brain stroke
- EF less than 20%
- History of alcohol abuse
- Epilepsy of history of psychiatric illness and antipsychotic drugs
- Patients with stenosis on carotid arteries
- Patients with preformed surgery or already stented carotid arteries
- Patients with poor or absent acoustic temporal window
- Diagnosed dementia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Impact of Intraoperative Microemboli Load on Postoperative Brain Injury in Patients Undergoing Aortic Valve Replacement Preformed With Two Different Surgical Approaches
Postoperative brain damage and neuropsychological disorders have been observed in 30 - 80 % of patients after heart surgery with the use of cardiopulmonary bypass (CPB).They can persist up to a year after cardiac surgery and are associated with increased hospital mortality and prolonged intrahospital stay.
Hypoperfusion,hyperthermia,atrial fibrillation,genetic predisposition and systemic inflammatory response associated with CPB have been identified as pathophysiological mechanisms.However, some authors consider cerebral embolisation to be the prevalent mechanism of intraoperative brain injury after cardiac surgery,as gaseous or solid cerebral emboli can cause ischemia, inflammation and edema,consequently causing cerebral infarctions usually resulting with stroke,coma,encephalopathy, delirium and cognitive decline. Additionally,they may impair cerebrovascular reactivity (CVR).
Read more
Aortic valve replacement (AVR) preformed by full sternotomy is the standard approach in the treatment of aortic valve disease. Minimally invasive (MIS) aortic valve replacement has been shown to reduce postoperative mortality, morbidity, and pain while providing faster recovery, a shorter hospital stay, and better cosmetic results. However, due to technically more demanding procedure, MIS may lead to prolonged CPB time and incomplete de-airing of the heart with an increased risk for cerebral gas embolization. Therefore, the choice of MIS might bear an augmented risk for brain injury.
Transcranial Doppler (TCD) enables real time detection of intraoperative emboli in the cerebral arteries seen as microembolic signals (MES), and is an essential neuromonitoring tool. Several studies demonstrated correlation between the number of MES and the occurrence as well as severity of postoperative neurological complications. However, the factors contributing to brain injury have not been elucidated in those studies. The investigators speculate that impairment of CVR is an important mechanism that persists and prolongs the duration of brain injury into postoperative period.
The aim of the study is to compare two surgical approaches used for AVR, with focus on the number of MES and their impact on levels of protein S100B (marker of brain tissue damage),postoperative CVR and cognitive function With the results,the investigators aim to help surgeons in selecting the appropriate technique for AVR in individual participants,as well as to clarify the effect of aortic valve surgery on the brain.
Read the detailed description
Patients undergoing for aortic valve replacement will be enrolled in the study after giving the signed informed consent and will be divided in two groups depending on the type of the surgical technique. Either full sternotomy (FS) or minimal invasive sternotomy (MIS) will be performed, both with the use of cardio-pulmonary bypass (CPB).One week before and one week after the surgery patients will undergo mini mental test and measurement of visually evoked cerebral blood flow velocity response (VEFR).Levels of S100B, interleukin (IL) 1, IL 6, IL 8, IL 10 and microparticles will be determined before induction of anesthesia,as well as 6 h, 24 h, 48 h and 7 days after CPB.Each patient will have invasive and non invasive monitoring that will include near infrared spectroscopy (NIRS), bispectral index (BIS) and TCD during surgery.MES will be detected using TCD at the following time-points: beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-airing, opening of the clamp on the aorta and after CBP removal before chest closure.All of this data will be documented as well as the demographic characteristics of patients, their preoperative medical status, and intraoperative data (duration of surgery, duration of CPB, hemodynamic parameters, inotropic/vasoactive support,blood and blood components); duration of mechanical ventilation in intensive care unit (ICU), duration of ICU stay, 30-day mortality and morbidity, as well as postoperative complications.
- Conditions
- Brain Injury
- Being tested
- Transcranial doppler
- Keywords
- Aortic valve surgery
- Medical subject headings
- Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial dopplerDevice
Prolonged de airing to decrease the number of MES
| Study group | Role | What they receive |
|---|---|---|
| AVR preformed with full sternotomy | Active comparator | 30 patients, 7 days before and after surgery mini mental test and measurement of visual evoked cerebral blood flow response (VEFR) will be done.
Transcranial doppler measurements 1. beginning of the surgery, 2.after sternotomy, 3.during aortic cannulation,4.during CPB,5. during de-airing, 6. opening of the clamp on the aorta, 7. after CPB removal before chest closure. Prolonged de airing if needed Receives: Device: Transcranial doppler |
| AVR preformed with minimal invasive sternotomy | Experimental | 30 patients, 7 days before and after surgery mini mental test and measurement of visual evoked cerebral blood flow response (VEFR) will be done.
Transcranial doppler measurements 1. beginning of the surgery, 2.after sternotomy, 3.during aortic cannulation,4.during CPB,5. during de-airing, 6. opening of the clamp on the aorta, 7. after CPB removal before chest closure. Prolonged de airing if needed Receives: Device: Transcranial doppler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of the intraoperative microembolic signals during minimal invasive sternotomy compared to full sternotomy with TCD during aortic valve surgery
Measured: Intraoperative detection:Beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-aeration, opening of the clamp on the aorta and after CBP removal before chest closure.
Detection of S100B serum protein, marker of brain tissue damage
Measured: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
Detection of serum interleukin IL-1, IL-6,IL-8,Il-10 and Microparticles
Measured: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
Secondary outcomes (2)
Assessment of cerebrovascular reactivity using visually evoked cerebral blood flow velocity response (VEFR) measurements
Measured: 7 days before and 7 days after surgery
Assessment of neurologic and cognitive function in patients undergoing AVR
Measured: 7 days before and 7 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startJan 2016
- Primary completionDec 2017 (estimated)
- Study completionApr 2018 (estimated)
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 Brain 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marija Bozhinovska
- Sponsor type
- University, hospital or other
- Collaborators
- Slovenian Research Agency
- Responsible party
- Sponsor-investigator, Marija Bozhinovska, University Medical Centre Ljubljana
- Investigators
- Maja Sostaric, MD, PhD, Study director, University Medical Centre LjubljanaMatej Podbregar, MD, PhD, Study director, University Medical Centre LjubljanaTomislav Klokocovnik, MD,PhD, Study director, University Medical Centre LjubljanaBorut Gersak, MD, PhD, Study director, University Medical Centre LjubljanaMarija Bozhinovska, MD, MSc, Principal investigator, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697786
- Sponsor's protocol ID
- ARRS-RPROJ - J R- 2014- 191
- Acronym
- IMLPBIAVR
- Status last verified
- Oct 2016
- First submitted
- 25 Jan 2016
- Last updated
- 28 Oct 2016
- Results posted
- No
- Individual data sharing
- Undecided
Publications
Bozhinovska M, Jenko M, Stupica GT, Klokocovnik T, Ksela J, Jelenc M, Podbregar M, Fabjan A, Sostaric M. Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study. J Cardiothorac Surg. 2021 May 24;16(1):142. doi: 10.1186/s13019-021-01509-8.
PubMed 34030698
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Intraoperative Microemboli Load on Postoperative Brain Injury in Patients Undergoing Aortic Valve Replacement Preformed With Two Different Surgical Approaches
- ClinicalTrials.gov ID
- NCT02697786
- Acronym / sponsor ID
- IMLPBIAVR / ARRS-RPROJ - J R- 2014- 191
- Conditions
- Brain Injury
- Keywords
- Aortic valve surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Marija BozhinovskaUniversity, hospital or other
- Collaborators
- Slovenian Research Agency
- Study start
- Jan 2016
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Apr 2018 (estimated)
- First posted
- 3 Mar 2016 (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.
Postoperative brain damage and neuropsychological disorders have been observed in 30 - 80 % of patients after heart surgery with the use of cardiopulmonary bypass (CPB).They can persist up to a year after cardiac surgery and are associated with increased hospital mortality and prolonged intrahospital stay.
Hypoperfusion,hyperthermia,atrial fibrillation,genetic predisposition and systemic inflammatory response associated with CPB have been identified as pathophysiological mechanisms.However, some authors consider cerebral embolisation to be the prevalent mechanism of intraoperative brain injury after cardiac surgery,as gaseous or solid cerebral emboli can cause ischemia, inflammation and edema,consequently causing cerebral infarctions usually resulting with stroke,coma,encephalopathy, delirium and cognitive decline. Additionally,they may impair cerebrovascular reactivity (CVR).
Aortic valve replacement (AVR) preformed by full sternotomy is the standard approach in the treatment of aortic valve disease. Minimally invasive (MIS) aortic valve replacement has been shown to reduce postoperative mortality, morbidity, and pain while providing faster recovery, a shorter hospital stay, and better cosmetic results. However, due to technically more demanding procedure, MIS may lead to prolonged CPB time and incomplete de-airing of the heart with an increased risk for cerebral gas embolization. Therefore, the choice of MIS might bear an augmented risk for brain injury.
Transcranial Doppler (TCD) enables real time detection of intraoperative emboli in the cerebral arteries seen as microembolic signals (MES), and is an essential neuromonitoring tool. Several studies demonstrated correlation between the number of MES and the occurrence as well as severity of postoperative neurological complications. However, the factors contributing to brain injury have not been elucidated in those studies. The investigators speculate that impairment of CVR is an important mechanism that persists and prolongs the duration of brain injury into postoperative period.
The aim of the study is to compare two surgical approaches used for AVR, with focus on the number of MES and their impact on levels of protein S100B (marker of brain tissue damage),postoperative CVR and cognitive function With the results,the investigators aim to help surgeons in selecting the appropriate technique for AVR in individual participants,as well as to clarify the effect of aortic valve surgery on the brain.
Detailed description
Patients undergoing for aortic valve replacement will be enrolled in the study after giving the signed informed consent and will be divided in two groups depending on the type of the surgical technique. Either full sternotomy (FS) or minimal invasive sternotomy (MIS) will be performed, both with the use of cardio-pulmonary bypass (CPB).One week before and one week after the surgery patients will undergo mini mental test and measurement of visually evoked cerebral blood flow velocity response (VEFR).Levels of S100B, interleukin (IL) 1, IL 6, IL 8, IL 10 and microparticles will be determined before induction of anesthesia,as well as 6 h, 24 h, 48 h and 7 days after CPB.Each patient will have invasive and non invasive monitoring that will include near infrared spectroscopy (NIRS), bispectral index (BIS) and TCD during surgery.MES will be detected using TCD at the following time-points: beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-airing, opening of the clamp on the aorta and after CBP removal before chest closure.All of this data will be documented as well as the demographic characteristics of patients, their preoperative medical status, and intraoperative data (duration of surgery, duration of CPB, hemodynamic parameters, inotropic/vasoactive support,blood and blood components); duration of mechanical ventilation in intensive care unit (ICU), duration of ICU stay, 30-day mortality and morbidity, as well as postoperative complications.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AVR preformed with full sternotomy | Active comparator | Device: Transcranial doppler30 patients, 7 days before and after surgery mini mental test and measurement of visual evoked cerebral blood flow response (VEFR) will be done. Transcranial doppler measurements 1. beginning of the surgery, 2.after sternotomy, 3.during aortic cannulation,4.during CPB,5. during de-airing, 6. opening of the clamp on the aorta, 7. after CPB removal before chest closure. Prolonged de airing if needed |
| AVR preformed with minimal invasive sternotomy | Experimental | Device: Transcranial doppler30 patients, 7 days before and after surgery mini mental test and measurement of visual evoked cerebral blood flow response (VEFR) will be done. Transcranial doppler measurements 1. beginning of the surgery, 2.after sternotomy, 3.during aortic cannulation,4.during CPB,5. during de-airing, 6. opening of the clamp on the aorta, 7. after CPB removal before chest closure. Prolonged de airing if needed |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Isolated aortic valve stenosis as well as asymptomatic patients with depressed systolic function
- Symptomatic patients with normal or depressed left ventricular function
- Patients with American Society of Anesthesiologist (ASA) physical status classification 2 or 3
Key exclusion criteria (8 listed)
- History of brain stroke
- EF less than 20%
- History of alcohol abuse
- Epilepsy of history of psychiatric illness and antipsychotic drugs
- Patients with stenosis on carotid arteries
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 |
|---|---|---|
| Transcranial dopplerProlonged de airing to decrease the number of MES | Device | AVR preformed with full sternotomy, AVR preformed with minimal invasive sternotomy |
Primary outcome
Detection of the intraoperative microembolic signals during minimal invasive sternotomy compared to full sternotomy with TCD during aortic valve surgery
Time frame: Intraoperative detection:Beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-aeration, opening of the clamp on the aorta and after CBP removal before chest closure.
Detection of S100B serum protein, marker of brain tissue damage
Time frame: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
Detection of serum interleukin IL-1, IL-6,IL-8,Il-10 and Microparticles
Time frame: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
2 secondary outcomes
Assessment of cerebrovascular reactivity using visually evoked cerebral blood flow velocity response (VEFR) measurements
Time frame: 7 days before and 7 days after surgery
Assessment of neurologic and cognitive function in patients undergoing AVR
Time frame: 7 days before and 7 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2016.
- Derived from this study: PubMed 34030698Bozhinovska M, Jenko M, Stupica GT, Klokocovnik T, Ksela J, Jelenc M, Podbregar M, Fabjan A, Sostaric M. Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study. J Cardiothorac Surg. 2021 May 24;16(1):142. doi: 10.1186/s13019-021-01509-8.
- Individual participant dataSharing planned: Undecided
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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.
Maja Sostaric, MD, PhD study director
University Medical Centre Ljubljana
Matej Podbregar, MD, PhD study director
University Medical Centre Ljubljana
Tomislav Klokocovnik, MD,PhD study director
University Medical Centre Ljubljana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Transcranial doppler in people with Brain Injury, run by Marija Bozhinovska at 1 site in Slovenia.
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 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: status not confirmed, as of the sponsor's last update on 28 Oct 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 Slovenia. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Detection of the intraoperative microembolic signals during minimal invasive sternotomy compared to full sternotomy with TCD during aortic valve surgery (time frame: Intraoperative detection:Beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-aeration, opening of the clamp on the aorta and after CBP removal before chest closure.). The study lists 3 primary outcomes in all. 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 NCT02697786, 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 28 Oct 2016.