Clinical trial NCT03377049: Acetazolamide Challenge With Perfusion in the Prediction of Cerebral Vasospasm
Official title: C-arm Cone Beam CTA and CTP With Acetazolamide Challenge in Aneurysmal Subarachnoid Hemorrhage: Evaluating Predictability for Early Ischemia in Cerebral Vasospasm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Vasospasm, Cerebral
Keywords: acetazolamide challenge
cerebral vasospasm
aneurysmal subarachnoid hemorrhage
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2017-12-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Develop Delayed Cerebral Vasospasm
timeFrame: Day 1-14 during the hospitalization
Secondary outcomes:
measure: Relative Percent Change in Cerebral Blood Flow
timeFrame: pre and post perfusion during imaging procedure, up to an hour
measure: Percent Change in Left Hemisphere Brain Imaging Maps
timeFrame: pre and post perfusion during imaging procedure, up to an hour
measure: Percent Change in Right Hemisphere Brain Imaging Maps
timeFrame: pre and post perfusion during imaging procedure, up to an hour
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Azam Ahmed, MD
role: PRINCIPAL_INVESTIGATOR
References:
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