Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Cerebral
Conditions
Keywords
acetazolamide challenge, cerebral vasospasm, aneurysmal subarachnoid hemorrhage
Brief summary
The investigators propose a technique using cone beam CT perfusion (CBCTP) imaging with an acetazolamide challenge as a potential diagnostic tool to detect a defect in cerebral autoregulation at a time when it has not yet caused clinically apparent signs or symptoms. 30 participants will be enrolled at the University of Wisconsin - Madison and can expect to be on study for about 2 weeks.
Detailed description
Acetazolamide or vasodilatory challenge should identify subjects having a abnormal cerebrovascular reactivity capacity. More specifically, after receiving the drug there will not be the expected increase in cerebral blood flow (CBF) in some of the subjects because they are already suffering from a disturbance in the vasculature's ability to respond to the signal for vasodilation. The investigators believe the presence of this deficit will be helpful in identifying patients who are at risk for potential brain ischemia due to this decreased capacity to autoregulate if/when clinically significant vasospasm occurs. The investigators predict that acetazolamide-activated regional cerebral blood flow studies will be more sensitive in the detection of mild cerebral vasospasm and will not just detect changes in cerebral blood flow as does standard perfusion imaging, but will provide information regarding changes in cerebrovascular reactivity. Under these circumstances, a better predictor of those patients at risk of cerebral infarction due to delayed vasospasm would be delineated. Identifying this high-risk cohort prior to the onset of clinically apparent symptoms would result in the institution of preventative measures such as triple H therapy. The objective of this proposal is to conduct a feasibility study of acetazolamide activated C-arm cone beam CT perfusion (CBCTP) to determine its application in the prediction of symptomatic cerebral vasospasm (i.e. ischemia or stroke) in patients with aneurysmal subarachnoid hemorrhage. The initial plan is to obtain C-arm CBCTP pre- and post-intravenous infusion of 1g acetazolamide within 24 hours of symptom onset in aneurysmal subarachnoid hemorrhage patients. The hypothesis is that some of these patients that will later develop clinical vasospasm of a degree sufficient to cause cerebral ischemia. The investigators believe this cohort of patients will demonstrate altered cerebrovascular reactivity during the acetazolamide challenge at a time before there is either angiographic evidence of vasospasm or clinical evidence of abnormal perfusion.
Interventions
DRUGAcetazolamide
1 g acetazolamide through a peripheral IV line
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with aneurysmal subarachnoid hemorrhage presenting to our institution within 24 hours of symptom onset * Adults, 18 years of age or older * Women of childbearing potential must not be pregnant (negative urine pregnancy test)
Exclusion criteria
* Contraindication to acetazolamide (i.e. sulfonamide allergy, renal or liver failure) * Contraindication to contrast media (Allergy or abnormal serum Cr and/or GFR based on current UW guidelines for IV contrast) * Renal insufficiency, history of renal failure or renal transplant * Hunt and Hess grade 1 and 5 (Attached protocol provides details on the grading scale. Grade 1 have lowest yield for vasospasm and Grade 5 are by definition critically ill and unstable patients) * Critically ill patients who are unstable and who cannot undergo scans within the proposed timeline i.e. within 24 hours of the onset of their symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Develop Delayed Cerebral Vasospasm | Day 1-14 during the hospitalization | Clinical neurological deterioration not attributable to other causes, mores specifically not due to re-bleeding, hydrocephalus, or metabolic changes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Percent Change in Cerebral Blood Flow | pre and post perfusion during imaging procedure, up to an hour | The data that will be statistically compared is the pre-diamox perfusion in comparison to the post-diamox perfusion. A statistically significant change increase in CBF represents an appropriate response to Diamox. Lack of change in CBF or decrease in CBF could be suggestive of potential for developing vasospasm. |
| Percent Change in Left Hemisphere Brain Imaging Maps | pre and post perfusion during imaging procedure, up to an hour | Using perfusion map values, relative percent change will be calculated |
| Percent Change in Right Hemisphere Brain Imaging Maps | pre and post perfusion during imaging procedure, up to an hour | Using perfusion map values, relative percent change will be calculated |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from July 2019 to April 2022.
Participants by arm
| Arm | Count |
|---|---|
| Acetazolamide Challenge Participants entered into the study as a cohort, will because of their participation, undergo only two additional digital subtraction angiogram (DSA) imaging acquisitions. These will be done in conjunction with their standard diagnostic DSA evaluation and consist of two CBCTPs, one before and one after administration of 1 g acetazolamide through a peripheral IV line. Each CBCTP will require administration of 75-100 mL iodinated contrast medium also through an intravenous line. Neither of these imaging studies will be used for clinical decision making, but would be processed and evaluated at later date for a formal analysis of the results. Following completion of diagnostic imaging subjects will receive the usual standard of care for treatment of their ruptured aneurysm i.e. endovascular embolization or open surgical clipping. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Acetazolamide Challenge |
|---|---|
| Age, Customized 30-39 years | 2 Participants |
| Age, Customized 40-49 years | 0 Participants |
| Age, Customized 50-59 years | 3 Participants |
| Age, Customized 60-69 years | 3 Participants |
| Age, Customized 70-79 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 11 |
| other Total, other adverse events | 1 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Number of Participants Who Develop Delayed Cerebral Vasospasm
Clinical neurological deterioration not attributable to other causes, mores specifically not due to re-bleeding, hydrocephalus, or metabolic changes.
Time frame: Day 1-14 during the hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide Challenge | Number of Participants Who Develop Delayed Cerebral Vasospasm | 2 Participants |
Secondary
Percent Change in Left Hemisphere Brain Imaging Maps
Using perfusion map values, relative percent change will be calculated
Time frame: pre and post perfusion during imaging procedure, up to an hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide Challenge | Percent Change in Left Hemisphere Brain Imaging Maps | 19.785 percent change | Standard Deviation 13.488 |
Secondary
Percent Change in Right Hemisphere Brain Imaging Maps
Using perfusion map values, relative percent change will be calculated
Time frame: pre and post perfusion during imaging procedure, up to an hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide Challenge | Percent Change in Right Hemisphere Brain Imaging Maps | 21.659 percent change | Standard Deviation 15.046 |
Secondary
Relative Percent Change in Cerebral Blood Flow
The data that will be statistically compared is the pre-diamox perfusion in comparison to the post-diamox perfusion. A statistically significant change increase in CBF represents an appropriate response to Diamox. Lack of change in CBF or decrease in CBF could be suggestive of potential for developing vasospasm.
Time frame: pre and post perfusion during imaging procedure, up to an hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide Challenge | Relative Percent Change in Cerebral Blood Flow | 20.722 percent change | Standard Deviation 13.967 |