Ignite Creation Date:
2024-05-06 @ 6:28 PM
Last Modification Date:
2024-10-26 @ 2:48 PM
Study NCT ID:
NCT05675774
Status:
RECRUITING
Last Update Posted:
2024-01-19
First Post:
2022-11-14
Brief Title:
DECT for Differentiating Intracerebral Hemorrhage From Contrast Extravasation
Sponsor:
University of Manitoba
Organization:
University of Manitoba
Study Overview
Official Title:
Dual Energy CT for Confirming Hemorrhagic Transformation After Thrombectomy for Patients With Acute Ischemic Stroke
Status:
RECRUITING
Status Verified Date:
2024-01
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:
DECT-ICH
Brief Summary:
The goal of this clinical trial is to investigate the use of DECT Dual-Energy Computed Tomography in patients with acute ischemic stroke who receive an intervention thrombolysis or thrombectomy The main questions to answer are
1 Can DECT more accurately differentiate hyperdensities as intracranial haemorrhage ICH or contrast extravasation compared with single-energy CT SECT
2 Will DECT lead to better care for patients with AIS who receive intervention and have post-procedural hyperdensities
Patients who receive intervention for acute ischemic stroke AIS receive a SECT at 24 hours as standard of care to determine if ICH is present In the current study a DECT will be done in addition to the SECT Followup imaging SECT or MRI will be done at 72 hours to determine if the hyperdensity was indeed ICH The accuracy of DECT for differentiating ICH from contrast extravasation will be compared
1 Can DECT more accurately differentiate hyperdensities as intracranial haemorrhage ICH or contrast extravasation compared with single-energy CT SECT
2 Will DECT lead to better care for patients with AIS who receive intervention and have post-procedural hyperdensities
Patients who receive intervention for acute ischemic stroke AIS receive a SECT at 24 hours as standard of care to determine if ICH is present In the current study a DECT will be done in addition to the SECT Followup imaging SECT or MRI will be done at 72 hours to determine if the hyperdensity was indeed ICH The accuracy of DECT for differentiating ICH from contrast extravasation will be compared
Detailed Description:
Background
Stroke is a leading cause of death in the world and the majority of strokes are ischemic 80 The first method of treating acute ischemic AIS is tissue plasminogen activator tPA1 2 which is a thrombolytic medication that breaks up the blockage in the blood vessel The second is called endovascular thrombectomy EVT which is a procedure where the clot is physically retrieved using a catheter3 While tPA can only be used within 45 hours EVT can be used 16 hours4 and even up to 24 hours5 after a patient develops symptoms
The go-to modality for imaging AIS is computed tomography CT6 7 On a CT scan image those objects that are brighter are hyperdense and those objects that are darker are hypodense To determine the location of the blockage and complete the EVT procedure contrast dye is used in combination with the CT In patients presenting with delayed AIS the CT-Perfusion CTP modality is also used which can determine tissue that is receiving less blood flow but has not infarcted yet Interestingly CTP can also generate information about the permeability of the blood-brain barrier which can be used to create a permeability-surface area product map PS Previous work by our group has demonstrated that using PS the likelihood not extent of hemorrhagic transformation can be predicted8
Both tPA and EVT can lead to the complication of intracerebral hemorrhage ICH If ICH develops in a patient following AIS the care-plan and prognosis is very different Another complication albeit less dangerous is contrast extravasation CE into the region of the stroke Contrast disappears after one to two days and does not affect the patient clinically It is standard of care to perform a CT scan 24 hours after a patient receives AIS intervention to rule out ICH Conventional single-energy CT SECT uses one x-ray spectrum Because contrast and blood are both significantly denser compared to surrounding tissue they appear identical to one another In dual-energy CT DECT two different x-ray spectra are used to create an additional iodine overlay map IOM and a virtual-noncontrast images 9-11 By using the IOM and VNC images in conjunction with original SECT image one can differentiate ICH from CE Figure 1 DECT does not expose patients the higher levels of radiation compared to SECT and can be a useful technique for differentiating objects on CT
We will perform a study looking at whether DECT can accurately identify hyperdensities caused from hemorrhage versus contrast We will validate the role of DECT in post stroke care for those patients that undergo EVT and have post procedural hyperdensities
Hypothesis
DECT will have a greater sensitivity and specificity for differentiating between ICH and CE compared to SECT in patients with AIS who receive acute intervention
Objectives
1 To determine whether DECT can accurately identify hyperdensities caused from hemorrhage versus contrast
2 To validate the role of DECT in post stroke care for those patients that undergo intervention and have post procedural hyperdensities
Methods
Outcome Measures
Our primary outcome is the sensitivity and specificity of DECT in differentiating ICH from CE
Our secondary outcomes include duration of hospitalization level of disability after discharge from hospital mechanism of large artery occlusion type of post-stroke therapy antiplatelet vs anticoagulant
Patient Selection All patients will be selected prospectively In Manitoba the Health Sciences Centre HSC is the only institution that provides EVT Therefore the patient population for our study includes the entire population served by HSC which includes the province of Manitoba north-western Ontario and southern Nunavut
Criteria
Inclusion criteria for our study are as follows patients presenting with AIS that are candidates for 1 tPA presenting within 45 hours of symptom onset no ICH on CT not on anticoagulation and 2 EVT presenting within 24 hours of symptom onset large vessel occlusion National Institute of Health Stroke Scale NIHSS 6
Exclusion criteria are patients who are not candidates for EVT or tPA Sample Size Sample size was calculated using the formula sample size p1-pZE2 The confidence interval was set at 95 and therefore Z was set at 196 and the desired margin of error E was set at 005 Previously it has been proposed that the proportion of patients that develop ICH post-EVT for AIS was more than 6812 Based on our experience we hypothesize that a hyperdensity could be seen in up to 85 of patients undergoing AIS treatment on their 24-hr post treatment CT scan of their head Therefore 085 was used as the value for population proportion p With this calculation the ideal sample size for recruitment would be 196 We will aim for a sample size of 200 With this selected sample size the resulting margin of error would be 006 which we found to be acceptable
Imaging Protocols The standard of care is to perform a non-contrast CT and CT with contrast when patients first present with symptoms of AIS If patients receive tPA andor EVT they undergo a non-contrast CT scan 24 hours post-treatment We will be performing DECT in addition to the standard-of-care SECT at 24 hours The amount of radiation generated by DECT is the same if not less than that generated by SECT13
In patients who have a hyperdensity on 24-hour CT a repeat scan either CT or MRI will be done at 72-hours post-intervention The 72-hour scan will be used as the gold-standard to determine if the hyperdensity on 24-hour CT was indeed ICH or CE
Imaging Data Collection and Analysis Images will be reviewed by all trained subspeciality neuroradiologists working at the Health Sciences Center
The study population will first be separated into two categories patients 1 with and 2 without hyperdensity seen on post-24 hour SECT scan Of the patients with hyperdensity we will further categorize them into four groups 1 Diagnosed as ICH on SECT and 2 diagnosed as CE on SECT 3 Diagnosed as ICH on DECT 4 Diagnosed as CE on DECT Finally of the patients with initial hyperdensity of 24-hour scan it will be determined if the hyperdensity is still present on 72-hour scan if it is still present the diagnosis will be confirmed as ICH
Statistical Analysis
Analysis will be performed by SPSS software Continuous data will be expressed as means standard deviations or 95 confidence intervals and categorical data will be expressed as numbers of patients with percentages respectively Sensitivity specificity positive predictive value negative predictive value and accuracy of DECT for identifying ICH will be recorded Statistical significance will be calculated using Fisher exact test A 2-sided P value less than 005 will be considered to indicate a significant difference We will perform receiver operating characteristic curve analyses to calculate the area under the curve AUC The optimal cutoff values for all parameters will be determined by the Youden index the difference between sensitivity and 1- specificity Diagnostic performance will be compared by using ROC analysis with the DeLong method
Expected outcome This study will determine if DECT is superior to SECT in differentiating ICH from CE and will validate the use of DECT in patients with AIS who receive intervention
Significance Stroke is a leading cause of death in the world In 2013 there were 405000 individuals in Canada living with the effects of stroke and this number is expected to increase to about 700000 by 203814 In Manitoba alone about 2000 patients each year suffer from a stroke and up to 500 will have a recurrent stroke To decrease the risk of subsequent strokes physicians target optimal blood pressure blood sugar and blood thinner management as soon as is safe for the patient Thrombolytic thrombectomy therapies have been shown to decrease the disability suffered by Manitobans who present with AIS but a significant proportion of these patients develop ICH These patients care is separate from those that do not develop ICH and are aimed toward decreasing the bleeding instead of preventing recurrent stroke The start of antiplatelet and anticoagulation therapies which have been shown to decrease the likelihood of subsequent stroke the earlier they are started must be delayed Blood pressure goals are also separate for these patients
If DECT is validated for the use in Manitobans who present with AIS who receive intervention clinicians will be able to determine more accurately whether a patient truly has an ICH and if their therapy needs to be modified accordingly Those patients who are determined to just have CE on DECT will not need to have their management needlessly changed and their care can be targeted toward avoiding recurrent stroke The use of DECT will lead to more diagnostic accuracy for those Manitobans presenting with AIS and more effective patient-directed care
Stroke is a leading cause of death in the world and the majority of strokes are ischemic 80 The first method of treating acute ischemic AIS is tissue plasminogen activator tPA1 2 which is a thrombolytic medication that breaks up the blockage in the blood vessel The second is called endovascular thrombectomy EVT which is a procedure where the clot is physically retrieved using a catheter3 While tPA can only be used within 45 hours EVT can be used 16 hours4 and even up to 24 hours5 after a patient develops symptoms
The go-to modality for imaging AIS is computed tomography CT6 7 On a CT scan image those objects that are brighter are hyperdense and those objects that are darker are hypodense To determine the location of the blockage and complete the EVT procedure contrast dye is used in combination with the CT In patients presenting with delayed AIS the CT-Perfusion CTP modality is also used which can determine tissue that is receiving less blood flow but has not infarcted yet Interestingly CTP can also generate information about the permeability of the blood-brain barrier which can be used to create a permeability-surface area product map PS Previous work by our group has demonstrated that using PS the likelihood not extent of hemorrhagic transformation can be predicted8
Both tPA and EVT can lead to the complication of intracerebral hemorrhage ICH If ICH develops in a patient following AIS the care-plan and prognosis is very different Another complication albeit less dangerous is contrast extravasation CE into the region of the stroke Contrast disappears after one to two days and does not affect the patient clinically It is standard of care to perform a CT scan 24 hours after a patient receives AIS intervention to rule out ICH Conventional single-energy CT SECT uses one x-ray spectrum Because contrast and blood are both significantly denser compared to surrounding tissue they appear identical to one another In dual-energy CT DECT two different x-ray spectra are used to create an additional iodine overlay map IOM and a virtual-noncontrast images 9-11 By using the IOM and VNC images in conjunction with original SECT image one can differentiate ICH from CE Figure 1 DECT does not expose patients the higher levels of radiation compared to SECT and can be a useful technique for differentiating objects on CT
We will perform a study looking at whether DECT can accurately identify hyperdensities caused from hemorrhage versus contrast We will validate the role of DECT in post stroke care for those patients that undergo EVT and have post procedural hyperdensities
Hypothesis
DECT will have a greater sensitivity and specificity for differentiating between ICH and CE compared to SECT in patients with AIS who receive acute intervention
Objectives
1 To determine whether DECT can accurately identify hyperdensities caused from hemorrhage versus contrast
2 To validate the role of DECT in post stroke care for those patients that undergo intervention and have post procedural hyperdensities
Methods
Outcome Measures
Our primary outcome is the sensitivity and specificity of DECT in differentiating ICH from CE
Our secondary outcomes include duration of hospitalization level of disability after discharge from hospital mechanism of large artery occlusion type of post-stroke therapy antiplatelet vs anticoagulant
Patient Selection All patients will be selected prospectively In Manitoba the Health Sciences Centre HSC is the only institution that provides EVT Therefore the patient population for our study includes the entire population served by HSC which includes the province of Manitoba north-western Ontario and southern Nunavut
Criteria
Inclusion criteria for our study are as follows patients presenting with AIS that are candidates for 1 tPA presenting within 45 hours of symptom onset no ICH on CT not on anticoagulation and 2 EVT presenting within 24 hours of symptom onset large vessel occlusion National Institute of Health Stroke Scale NIHSS 6
Exclusion criteria are patients who are not candidates for EVT or tPA Sample Size Sample size was calculated using the formula sample size p1-pZE2 The confidence interval was set at 95 and therefore Z was set at 196 and the desired margin of error E was set at 005 Previously it has been proposed that the proportion of patients that develop ICH post-EVT for AIS was more than 6812 Based on our experience we hypothesize that a hyperdensity could be seen in up to 85 of patients undergoing AIS treatment on their 24-hr post treatment CT scan of their head Therefore 085 was used as the value for population proportion p With this calculation the ideal sample size for recruitment would be 196 We will aim for a sample size of 200 With this selected sample size the resulting margin of error would be 006 which we found to be acceptable
Imaging Protocols The standard of care is to perform a non-contrast CT and CT with contrast when patients first present with symptoms of AIS If patients receive tPA andor EVT they undergo a non-contrast CT scan 24 hours post-treatment We will be performing DECT in addition to the standard-of-care SECT at 24 hours The amount of radiation generated by DECT is the same if not less than that generated by SECT13
In patients who have a hyperdensity on 24-hour CT a repeat scan either CT or MRI will be done at 72-hours post-intervention The 72-hour scan will be used as the gold-standard to determine if the hyperdensity on 24-hour CT was indeed ICH or CE
Imaging Data Collection and Analysis Images will be reviewed by all trained subspeciality neuroradiologists working at the Health Sciences Center
The study population will first be separated into two categories patients 1 with and 2 without hyperdensity seen on post-24 hour SECT scan Of the patients with hyperdensity we will further categorize them into four groups 1 Diagnosed as ICH on SECT and 2 diagnosed as CE on SECT 3 Diagnosed as ICH on DECT 4 Diagnosed as CE on DECT Finally of the patients with initial hyperdensity of 24-hour scan it will be determined if the hyperdensity is still present on 72-hour scan if it is still present the diagnosis will be confirmed as ICH
Statistical Analysis
Analysis will be performed by SPSS software Continuous data will be expressed as means standard deviations or 95 confidence intervals and categorical data will be expressed as numbers of patients with percentages respectively Sensitivity specificity positive predictive value negative predictive value and accuracy of DECT for identifying ICH will be recorded Statistical significance will be calculated using Fisher exact test A 2-sided P value less than 005 will be considered to indicate a significant difference We will perform receiver operating characteristic curve analyses to calculate the area under the curve AUC The optimal cutoff values for all parameters will be determined by the Youden index the difference between sensitivity and 1- specificity Diagnostic performance will be compared by using ROC analysis with the DeLong method
Expected outcome This study will determine if DECT is superior to SECT in differentiating ICH from CE and will validate the use of DECT in patients with AIS who receive intervention
Significance Stroke is a leading cause of death in the world In 2013 there were 405000 individuals in Canada living with the effects of stroke and this number is expected to increase to about 700000 by 203814 In Manitoba alone about 2000 patients each year suffer from a stroke and up to 500 will have a recurrent stroke To decrease the risk of subsequent strokes physicians target optimal blood pressure blood sugar and blood thinner management as soon as is safe for the patient Thrombolytic thrombectomy therapies have been shown to decrease the disability suffered by Manitobans who present with AIS but a significant proportion of these patients develop ICH These patients care is separate from those that do not develop ICH and are aimed toward decreasing the bleeding instead of preventing recurrent stroke The start of antiplatelet and anticoagulation therapies which have been shown to decrease the likelihood of subsequent stroke the earlier they are started must be delayed Blood pressure goals are also separate for these patients
If DECT is validated for the use in Manitobans who present with AIS who receive intervention clinicians will be able to determine more accurately whether a patient truly has an ICH and if their therapy needs to be modified accordingly Those patients who are determined to just have CE on DECT will not need to have their management needlessly changed and their care can be targeted toward avoiding recurrent stroke The use of DECT will lead to more diagnostic accuracy for those Manitobans presenting with AIS and more effective patient-directed care
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None