Ignite Creation Date:
2024-05-06 @ 3:00 AM
Last Modification Date:
2024-10-26 @ 11:26 AM
Study NCT ID:
NCT02177981
Status:
COMPLETED
Last Update Posted:
2018-04-25
First Post:
2014-04-07
Brief Title:
Impact of Remote Ischemic Preconditioning Preceding Coronary Artery Bypass Grafting on Inducing nEuroprotection
Sponsor:
University of Zagreb
Organization:
University of Zagreb
Study Overview
Official Title:
A Randomized Double-Blind Controlled Clinical Trial Impact of Remote Ischemic Preconditioning Preceding Coronary Artery Bypass Grafting on Inducing Neuroprotection
Status:
COMPLETED
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RIPCAGE
Brief Summary:
Coronary artery disease CAD is the leading cause of death worldwide Patients with severe CAD are often treated with coronary artery bypass grafting CABG Novel treatment strategies need to be pursued to respond to the continuous increase in the risk profile of contemporary CABG patients Surgical myocardial revascularization is commonly performed with the use of cardiopulmonary bypass CPB Neurological impairment following CABG may take on the form of a new-onset motor deficit or postoperative cognitive dysfunction The former is rare but potentially devastating Conversely declines in attention memory and fine motor skills can frequently be documented
Ischemic preconditioning is a phenomenon of an endogenous protective response to organ ischemia which is triggered by brief cycles of nonlethal ischemia and reperfusion in tissues known to be more resistant to ischemic insults In clinical practice remote ischemic preconditioning RIPC is achieved by inflicting short periods of ischemia with intermittent restitution of flow to the upper extremity This intervention has been shown to be effective in the reduction of myocardial injury in cardiac surgical patients The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neurological injury following CABG
In this research project 70 patients scheduled for an elective CABG will be recruited at a single center They will be randomly allocated to either undergo RIPC intervention arm or a sham procedure control arm Inflating a blood pressure cuff to 200 mmHg for 5 min will induce RIPC thereby inducing a brief period of ischemia This will be followed by a 5-minute arm reperfusion In total three cycles of arm ischemia and reperfusion will be induced in this fashion
All patients will undergo pre- and post-procedural magnetic resonance imaging MRI of the brain as well as neurocognitive testing The array of MRI tools that will be used for the quantification of brain injury will include fluid attenuated inversion recovery diffusion weighted and susceptibility weighted imaging coupled with resting state functional MRI
The investigators aim to determine whether RIPC can reduce the adverse impact of CPB on neurological outcome as evaluated by MRI detectable brain ischemia and neurocognition
Ischemic preconditioning is a phenomenon of an endogenous protective response to organ ischemia which is triggered by brief cycles of nonlethal ischemia and reperfusion in tissues known to be more resistant to ischemic insults In clinical practice remote ischemic preconditioning RIPC is achieved by inflicting short periods of ischemia with intermittent restitution of flow to the upper extremity This intervention has been shown to be effective in the reduction of myocardial injury in cardiac surgical patients The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neurological injury following CABG
In this research project 70 patients scheduled for an elective CABG will be recruited at a single center They will be randomly allocated to either undergo RIPC intervention arm or a sham procedure control arm Inflating a blood pressure cuff to 200 mmHg for 5 min will induce RIPC thereby inducing a brief period of ischemia This will be followed by a 5-minute arm reperfusion In total three cycles of arm ischemia and reperfusion will be induced in this fashion
All patients will undergo pre- and post-procedural magnetic resonance imaging MRI of the brain as well as neurocognitive testing The array of MRI tools that will be used for the quantification of brain injury will include fluid attenuated inversion recovery diffusion weighted and susceptibility weighted imaging coupled with resting state functional MRI
The investigators aim to determine whether RIPC can reduce the adverse impact of CPB on neurological outcome as evaluated by MRI detectable brain ischemia and neurocognition
Detailed Description:
Coronary artery bypass grafting CABG is very effective in the management of complex coronary artery disease CAD Cardiopulmonary bypass CPB is commonly employed to achieve a still and bloodless field which facilitates the creation of technically impeccable coronary anastomoses Multiple adverse effects that stem from exposure of blood to a non-endothelial surface contrast the clear benefit of CPB Neurological damage remains one of the most dreaded complications following CABG While the incidence of new focal motor deficits is low postoperative neurocognitive dysfunction POCD is seen commonly The increasing risk profile of contemporary CABG patients makes neuroprotective strategies progressively more important
Ischemic preconditioning is an endogenous protective response triggered by brief episodes of nonlethal ischemia and reperfusion In clinical practice remote ischemic preconditioning RIPC is achieved by inducing short periods of ischemia of the upper extremity followed by restitution of flow This non-pharmacological strategy for inducing ischemic tolerance is cost-free and non-invasive with potentially wide clinical applicability
The Impact of Remote Ischemic Preconditioning preceding Coronary Artery bypass Grafting on inducing nEuroprotection RIPCAGE trial will recruit 70 patients scheduled for elective CABG at a single academic center The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neuronal damage and lead to a reduction in POCD among CABG patients Specifically the investigators aim to determine whether RIPC can reduce magnetic resonance imaging MRI detectable brain damage and attenuate the neurocognitive decline universally seen in patients after CABG
The primary composite outcome will consist of a composite of new ischemic lesions on brain MRI and POCD
The secondary endpoints will be the following
1 Brain connectivity profiles on resting-state functional MRI rs-fMRI
2 Pooled ischemic volumes of new diffusion-weighted imaging DWI hyperintensity
3 Percent declines of components in individual neurocognitive tests
Patients will be randomly allocated in a 11 ratio to either receive RIPC or no intervention control group In the intervention arm transient upper extremity ischemia will be induced after induction of anesthesia by inflating a blood pressure cuff to 200 mmHg for 5 min followed by a 5 min cuff deflation This sequence will be repeated 3 times Patients in the control group will also have a blood pressure cuff placed but it will not be inflated All patients will undergo preoperative neurocognitive testing coupled with baseline brain MRI The neurocognitive evaluation will consist of the Montreal Cognitive Assessment MoCA test and the Trail Making Test TMT Decreased cognitive function for each test will be defined as an individual decrease of at least 1 standard deviation of the group baseline mean for that test POCD will be defined as a decrease in two or more tests The patients will have a repeat neurocognitive evaluation prior to discharge from hospital
Standard MRI sequences will be performed in all patients DWI will be utilized for volumetric analysis of brain tissue exhibiting stigmata of ischemic injury The timing of apparent diffusion coefficient quantification will be standardized to postoperative day 7 as it normalizes over time Additional MRI sequences will include susceptibility weighted imaging SWI and diffusion tensor imaging DTI Resting state functional MRI will be performed in order to investigate the coordination of activity across brain networks Pre- and postprocedural rs-fMRI data will be subsequently compared with each other Disruption in the connectivity of neural circuits induced by the operation will be thereby be objectivized
Patients will be followed for a total of 3 months during which time all adverse events will be recorded and adjudicated by an independent clinical events committee
Ischemic preconditioning is an endogenous protective response triggered by brief episodes of nonlethal ischemia and reperfusion In clinical practice remote ischemic preconditioning RIPC is achieved by inducing short periods of ischemia of the upper extremity followed by restitution of flow This non-pharmacological strategy for inducing ischemic tolerance is cost-free and non-invasive with potentially wide clinical applicability
The Impact of Remote Ischemic Preconditioning preceding Coronary Artery bypass Grafting on inducing nEuroprotection RIPCAGE trial will recruit 70 patients scheduled for elective CABG at a single academic center The hypothesis tested in this research proposal is that RIPC will decrease the extent of postoperative neuronal damage and lead to a reduction in POCD among CABG patients Specifically the investigators aim to determine whether RIPC can reduce magnetic resonance imaging MRI detectable brain damage and attenuate the neurocognitive decline universally seen in patients after CABG
The primary composite outcome will consist of a composite of new ischemic lesions on brain MRI and POCD
The secondary endpoints will be the following
1 Brain connectivity profiles on resting-state functional MRI rs-fMRI
2 Pooled ischemic volumes of new diffusion-weighted imaging DWI hyperintensity
3 Percent declines of components in individual neurocognitive tests
Patients will be randomly allocated in a 11 ratio to either receive RIPC or no intervention control group In the intervention arm transient upper extremity ischemia will be induced after induction of anesthesia by inflating a blood pressure cuff to 200 mmHg for 5 min followed by a 5 min cuff deflation This sequence will be repeated 3 times Patients in the control group will also have a blood pressure cuff placed but it will not be inflated All patients will undergo preoperative neurocognitive testing coupled with baseline brain MRI The neurocognitive evaluation will consist of the Montreal Cognitive Assessment MoCA test and the Trail Making Test TMT Decreased cognitive function for each test will be defined as an individual decrease of at least 1 standard deviation of the group baseline mean for that test POCD will be defined as a decrease in two or more tests The patients will have a repeat neurocognitive evaluation prior to discharge from hospital
Standard MRI sequences will be performed in all patients DWI will be utilized for volumetric analysis of brain tissue exhibiting stigmata of ischemic injury The timing of apparent diffusion coefficient quantification will be standardized to postoperative day 7 as it normalizes over time Additional MRI sequences will include susceptibility weighted imaging SWI and diffusion tensor imaging DTI Resting state functional MRI will be performed in order to investigate the coordination of activity across brain networks Pre- and postprocedural rs-fMRI data will be subsequently compared with each other Disruption in the connectivity of neural circuits induced by the operation will be thereby be objectivized
Patients will be followed for a total of 3 months during which time all adverse events will be recorded and adjudicated by an independent clinical events committee
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None