Acetazolamide Challenge With Perfusion in the Prediction of Cerebral Vasospasm

University of Wisconsin (UW)

Status and phase: Completed; Phase 4

Conditions: Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral

Treatments: Drug: Acetazolamide

Study type: Interventional

Funder types: Other

Identifiers

NCT03377049

SMPH/NEURO SURG/NEURO SURG (Other Identifier)

Protocol Version 4/28/2020 (Other Identifier)

2017-1510

A535700 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 1 patient group

Acetazolamide Challenge

Experimental group

Description:

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.

Treatment:

Drug: Acetazolamide