Acetazolamide Challenge With Perfusion in the Prediction of Cerebral Vasospasm

NCT ID: NCT03377049

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-28
• Study Completion Date: 2022-07-15

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Acetazolamide

Intervention Type: DRUG

1 g acetazolamide through a peripheral IV line

Interventions

Acetazolamide

1 g acetazolamide through a peripheral IV line

Intervention Type: DRUG

Other Intervention Names

Diamox

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Azam Ahmed, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Shinoda J, Kimura T, Funakoshi T, Araki Y, Imao Y. Acetazolamide reactivity on cerebral blood flow in patients with subarachnoid haemorrhage. Acta Neurochir (Wien). 1991;109(3-4):102-8. doi: 10.1007/BF01403003.

Reference Type: BACKGROUND

PMID: 1858527 (View on PubMed)

Tanaka A, Yoshinaga S, Nakayama Y, Tomonaga M. Cerebral blood flow and the response to acetazolamide during the acute, subacute, and chronic stages of aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 1998 Oct;38(10):623-30; discussion 630-2. doi: 10.2176/nmc.38.623.

Reference Type: BACKGROUND

PMID: 9861845 (View on PubMed)

Lee KH, Lukovits T, Friedman JA. "Triple-H" therapy for cerebral vasospasm following subarachnoid hemorrhage. Neurocrit Care. 2006;4(1):68-76. doi: 10.1385/NCC:4:1:068.

Reference Type: BACKGROUND

PMID: 16498198 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 22179539 (View on PubMed)

Sullivan HG, Kingsbury TB 4th, Morgan ME, Jeffcoat RD, Allison JD, Goode JJ, McDonnell DE. The rCBF response to Diamox in normal subjects and cerebrovascular disease patients. J Neurosurg. 1987 Oct;67(4):525-34. doi: 10.3171/jns.1987.67.4.0525.

Reference Type: BACKGROUND

PMID: 3655890 (View on PubMed)

Hinson JS, Ehmann MR, Fine DM, Fishman EK, Toerper MF, Rothman RE, Klein EY. Risk of Acute Kidney Injury After Intravenous Contrast Media Administration. Ann Emerg Med. 2017 May;69(5):577-586.e4. doi: 10.1016/j.annemergmed.2016.11.021. Epub 2017 Jan 25.

Reference Type: BACKGROUND

PMID: 28131489 (View on PubMed)

Hauge A, Nicolaysen G, Thoresen M. Acute effects of acetazolamide on cerebral blood flow in man. Acta Physiol Scand. 1983 Feb;117(2):233-9. doi: 10.1111/j.1748-1716.1983.tb07202.x.

Reference Type: BACKGROUND

PMID: 6869033 (View on PubMed)

Kimura T, Shinoda J, Funakoshi T. Prediction of cerebral infarction due to vasospasm following aneurysmal subarachnoid haemorrhage using acetazolamide-activated 123I-IMP SPECT. Acta Neurochir (Wien). 1993;123(3-4):125-8. doi: 10.1007/BF01401867.

Reference Type: BACKGROUND

PMID: 8237489 (View on PubMed)

Bruce RJ, Djamali A, Shinki K, Michel SJ, Fine JP, Pozniak MA. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol. 2009 Mar;192(3):711-8. doi: 10.2214/AJR.08.1413.

Reference Type: BACKGROUND

PMID: 19234268 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SMPH/NEURO SURG/NEURO SURG

Identifier Type: OTHER

Identifier Source: secondary_id

A535700

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 4/28/2020

Identifier Type: OTHER

Identifier Source: secondary_id

2017-1510

Identifier Type: -

Identifier Source: org_study_id