Acetazolamide Challenge With Perfusion in the Prediction of Cerebral Vasospasm

NCT03377049 | Completed Phase 4 Results FDA Drug

• 4 other identifiers: 2017-1510SMPH/NEURO SURG/NEURO SURGA535700Protocol Version 4/28/2020
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral

Keywords

acetazolamide challenge; cerebral vasospasm; aneurysmal subarachnoid hemorrhage

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1-14 during the hospitalization

Secondary Outcomes (3)

• Relative Percent Change in Cerebral Blood Flow

  pre and post perfusion during imaging procedure, up to an hour

• Percent Change in Left Hemisphere Brain Imaging Maps

  pre and post perfusion during imaging procedure, up to an hour

• Percent Change in Right Hemisphere Brain Imaging Maps

  pre and post perfusion during imaging procedure, up to an hour

Study Arms (1)

Acetazolamide Challenge

EXPERIMENTAL

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.

Drug: Acetazolamide

Interventions

Acetazolamide DRUG

1 g acetazolamide through a peripheral IV line

Also known as: Diamox

Acetazolamide Challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (9)

• 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.

  PMID: 1858527 BACKGROUND

• 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.

  PMID: 9861845 BACKGROUND

• 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.

  PMID: 16498198 BACKGROUND

• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. No abstract available.

  PMID: 22179539 BACKGROUND

• 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.

  PMID: 3655890 BACKGROUND

• 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.

  PMID: 28131489 BACKGROUND

• 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.

  PMID: 6869033 BACKGROUND

• 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.

  PMID: 8237489 BACKGROUND

• 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.

  PMID: 19234268 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Azam Ahmed, MD, FAANS, FACS
• Organization: UW School of Medicine and Public Health

azam.ahmed@neurosurgery.wisc.edu

608-263-0485

Study Officials

• Azam Ahmed, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 19, 2017
• Study Start: July 28, 2019
• Primary Completion: July 15, 2022
• Study Completion: July 15, 2022
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)