Transcranial Ultrasound Via Sonolucent Cranioplasty After Minimally Invasive Intracerebral Hemorrhage Evacuation (TUSC MIS)

Postoperative rebleeding is a major limitation of surgical evacuation for intracerebral hemorrhage (ICH). While computed tomography (CT) is the standard of care for postoperative hematoma cavity monitoring, CT requires significant physical and financial costs. Studies have demonstrated varying degrees of efficacy when using transcranial ultrasound to measure ICH volume. Recently, synthetic implants for cranioplasty have been shown to be safe and sonolucent. This study aims to evaluate the ability of transcranial ultrasound with sonolucent cranioplasty (TUSC) to detect and quantify bleeding in postoperative ICH patients.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Ultrasound With Sonolucent Cranioplasty; TUSC
• Intervention / Treatment: Device: ClearFit implant; Procedure: transcranial ultrasonography through sonolucent cranioplasty

Detailed Description

Intracerebral hemorrhage (ICH) accounts for over 2 million strokes annually. ICH is the most devastating subtype of stroke, with a 1-year mortality rate of up to 50% and a 6-month survivor disability rate of up to 88%. Large-scale multicenter trials including STICH, STICH II, and MISTIE III demonstrated that surgical evacuation did not appear to improve long term functional outcome. Smaller studies and sub-group analyses have suggested that some forms of minimally invasive ICH evacuation may benefit specific patients. Postoperative rebleeding after surgical evacuation of ICH occurs in 5-40% and remains a major limitation to the efficacy and widespread adoption of this treatment strategy. Therefore, rapid assessment, detection, and management of postoperative bleeding is critical to maximize functional recovery after surgical evacuation.

The standard of care for postoperative hematoma cavity monitoring is computed tomography (CT). However, repeat CTs to assess patients with ICH incur health and financial cost including time and personnel to bring the patient to scan, risk of dislodging lines or drains, radiation dosing, and financial cost as well as others. Studies have demonstrated varying degrees of efficacy when using transcranial ultrasound to measure ICH volume. Recently, synthetic implants for cranioplasty have been shown to be safe and sonolucent. This study aims to evaluate the ability of transcranial ultrasound with sonolucent cranioplasty (TUSC) to detect and quantify bleeding in postoperative ICH patients.

In this prospective study, postoperative ICH patients will undergo cranioplasty with a sonolucent polymethyl methacrylate implant and serial monitoring via TUSC. Whenever a CT is performed during business hours, TUSC will be performed within 2 hours by a neurointensivist trained in point-of-care transcranial ultrasound (TCUS). Imaging will be reviewed by two independent neuroimaging experts. Additional secondary outcomes will include occurrence of serious adverse events, detection of intraventricular hemorrhage, and cost of care when compared to CT.

This work has the potential to significantly improve clinical management of ICH. This study will provide the safety and feasibility data necessary to guide future clinical research. ICH detection and volumetry are critical to patient care and prognostication. This point-of-care testing enables neurosurgeons to serially monitor patients to ensure that they receive timely, appropriate care.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher P. Kellner, MD; Phone Number: (212) 241-6500; Email: christopher.kellner@mountsinai.org
• Study Contact Backup: Name: Sydney Edwards; Email: Sydney.Edwards@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Health System
      • Contact: Christopher P. Kellner, MD; Email: christopher.kellner@mountsinai.org
      • Principal Investigator: Christopher P. Kellner
      • Contact: Sydney Edwards; Email: Sydney.Edwards@mountsinai.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Presence of spontaneous supratentorial ICH ≥20 mL
• Age ≥18 years
• National Institute of Health Stroke Scale (NIHSS) score ≥6
• GCS score 5-15 at presentation
• Undergoing minimally invasive intracerebral hemorrhage evacuation with sonolucent cranioplasty or hemicraniectomy with sonolucent cranioplasty

Exclusion criteria:

• Secondary cause for the ICH, such as an underlying vascular malformation (cavernous malformation, arteriovenous malformation, etc.), aneurysm, neoplasm, hemorrhagic transformation of an underlying ischemic infarct; or venous infarct
• History of osteomyelitis
• History of skull neoplasm
• History of comminuted skull fractures
• Infratentorial hemorrhage
• Midbrain extension/involvement
• Coagulopathy defined as INR > 1.4, elevated aPTT, or concurrent use of direct oral anticoagulants or low molecular weight heparin at ICH onset; known hereditary or acquired hemorrhagic diathesis; coagulation factor deficiency; platelet count < 100x103cells/mm3, or known platelet dysfunction
• Inability to obtain consent from patient or appropriate surrogate (for patients without capacity)
• Evidence of active infection indicated by fever ≥ 100.7F and/or open draining wound at the time of enrolment
• Any comorbid disease or condition expected to compromise survival or ability to complete follow-up assessments through 1 year
• Based on investigator's judgment, the patient does not have the necessary mental capacity to participate or is unwilling to comply with the protocol follow-up appointment schedule
• Active drug or alcohol abuse that, in the opinion of the site investigator, would interfere with adherence to study enrolments
• Pre-existing DNR/DNI status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: transcranial ultrasonography through sonolucent cranioplasty; All surgical procedures and implants in this protocol are standard of care.

Device: ClearFit implant; The ClearFit implant is an FDA cleared implant in regular use in the United States. The ClearFit implant and other PMMA cranioplasty implants manufactured by Longeviti have been reported to be safe and effective as cranial implants that permit transcranial ultrasound to be performed. The PMMA cranioplasty implant (Longeviti Neuro Solutions, Hunt Valley, MD) is clear, sonolucent, and was recently shown to be safe and effective in transcranial ultrasonography for bypass patency assessment. The ClearFit cranioplasty being used in this study is industry standard of care.; Procedure: transcranial ultrasonography through sonolucent cranioplasty; The implantation of the ClearFit PMMA sonolucent implant permits TUSC to be performed at the bedside for patients in both the in-patient and outpatient settings. While the patient is an inpatient, the clinical or research teams will attempt to perform TUSC within 1 hour of neuroimaging if that neuroimaging is performed at a time when a trained ultrasound operator is present.; Other Names: TUSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence of intracerebral hemorrhage	Accuracy of TUSC via ClearFit to detect the presence or absence of postoperative intracerebral hemorrhage compared to CT.	at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events related to ClearFit or TUSC	Serious Adverse Events related to ClearFit or TUSC	at 6 months
Accuracy of TUSC to detect intraventricular hemorrhage	Accuracy of TUSC to detect intraventricular hemorrhage compared to CT. Detection of intraventricular hemorrhage will be a categorical variable [present, absent].	at 6 months
Cost of TUSC	Cost of TUSC versus standard of care imaging (CT or MRI)	at 6 months
Reimbursement rates for TUSC	Reimbursement rates for TUSC as a point of care examination in the ICU and outpatient clinic	at 6 months
TUSC/CT ratio for distance between lateral ventricle frontal horns	TUSC/CT ratio to measure distance between lateral ventricle frontal horns.	at 6 months
TUSC/CT ratio for midline shift	TUSC/CT ratio to measure midline shift	at 6 months
Accuracy of TUSC to detect hydrocephalus	Detection of hydrocephalus will be a categorical variable based on ventricle morphology and size [present, absent]	at 6 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Christopher P. Kellner, MD, Mount Sinai Health System Department of Neurosurgery

Publications and helpful links

General Publications

• Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson LM, Truelsen T, O'Donnell M, Venketasubramanian N, Barker-Collo S, Lawes CM, Wang W, Shinohara Y, Witt E, Ezzati M, Naghavi M, Murray C; Global Burden of Diseases, Injuries, Risk Factors Study 2010 (GBD 2010); GBD Stroke Experts Group. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013 Nov;1(5):e259-81. doi: 10.1016/S2214-109X(13)70089-5. Epub 2013 Oct 24.
• Kellner CP, Song R, Pan J, Nistal DA, Scaggiante J, Chartrain AG, Rumsey J, Hom D, Dangayach N, Swarup R, Tuhrim S, Ghatan S, Bederson JB, Mocco J. Long-term functional outcome following minimally invasive endoscopic intracerebral hemorrhage evacuation. J Neurointerv Surg. 2020 May;12(5):489-494. doi: 10.1136/neurintsurg-2019-015528. Epub 2020 Jan 8.
• Niesen WD, Schlaeger A, Bardutzky J, Fuhrer H. Correct Outcome Prognostication via Sonographic Volumetry in Supratentorial Intracerebral Hemorrhage. Front Neurol. 2019 May 8;10:492. doi: 10.3389/fneur.2019.00492. eCollection 2019.
• Morgenstern LB, Demchuk AM, Kim DH, Frankowski RF, Grotta JC. Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage. Neurology. 2001 May 22;56(10):1294-9. doi: 10.1212/wnl.56.10.1294.
• Delcourt C, Huang Y, Arima H, Chalmers J, Davis SM, Heeley EL, Wang J, Parsons MW, Liu G, Anderson CS; INTERACT1 Investigators. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012 Jul 24;79(4):314-9. doi: 10.1212/WNL.0b013e318260cbba. Epub 2012 Jun 27.
• Flores AR, Srinivasan VM, Seeley J, Huggins C, Kan P, Burkhardt JK. Safety, Feasibility, and Patient-Rated Outcome of Sonolucent Cranioplasty in Extracranial-Intracranial Bypass Surgery to Allow for Transcranioplasty Ultrasound Assessment. World Neurosurg. 2020 Dec;144:e277-e284. doi: 10.1016/j.wneu.2020.08.114. Epub 2020 Aug 20.
• Kellner CP, Song R, Ali M, Nistal DA, Samarage M, Dangayach NS, Liang J, McNeill I, Zhang X, Bederson JB, Mocco J. Time to Evacuation and Functional Outcome After Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation. Stroke. 2021 Aug;52(9):e536-e539. doi: 10.1161/STROKEAHA.121.034392. Epub 2021 Jun 24.
• Fernando SM, Qureshi D, Talarico R, Dowlatshahi D, Sood MM, Smith EE, Hill MD, McCredie VA, Scales DC, English SW, Rochwerg B, Tanuseputro P, Kyeremanteng K. Short- and Long-term Health Care Resource Utilization and Costs Following Intracerebral Hemorrhage. Neurology. 2021 Aug 10;97(6):e608-e618. doi: 10.1212/WNL.0000000000012355. Epub 2021 Jun 9.
• Hadley C, North R, Srinivasan V, Kan P, Burkhardt JK. Elective Sonolucent Cranioplasty for Real-Time Ultrasound Monitoring of Flow and Patency of an Extra- to Intracranial Bypass. J Craniofac Surg. 2020 May/Jun;31(3):622-624. doi: 10.1097/SCS.0000000000006225.
• Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, Lane K, McBee N, Mayo SW, Bistran-Hall AJ, Gandhi D, Mould WA, Ullman N, Ali H, Carhuapoma JR, Kase CS, Lees KR, Dawson J, Wilson A, Betz JF, Sugar EA, Hao Y, Avadhani R, Caron JL, Harrigan MR, Carlson AP, Bulters D, LeDoux D, Huang J, Cobb C, Gupta G, Kitagawa R, Chicoine MR, Patel H, Dodd R, Camarata PJ, Wolfe S, Stadnik A, Money PL, Mitchell P, Sarabia R, Harnof S, Barzo P, Unterberg A, Teitelbaum JS, Wang W, Anderson CS, Mendelow AD, Gregson B, Janis S, Vespa P, Ziai W, Zuccarello M, Awad IA; MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019 Mar 9;393(10175):1021-1032. doi: 10.1016/S0140-6736(19)30195-3. Epub 2019 Feb 7.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: STUDY-21-01878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: In order to minimize any privacy risks to the patients participating, IPD data will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes