Transcranial Ultrasound Via Sonolucent Cranioplasty After Minimally Invasive Intracerebral Hemorrhage Evacuation

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Transcranial Ultrasound Via Sonolucent Cranioplasty After Minimally Invasive Intracerebral Hemorrhage Evacuation

Conditions
-----------------
Transcranial Ultrasound With Sonolucent Cranioplasty, TUSC

Intervention / Treatment
-----------------
* Device: ClearFit implant
* Procedure: transcranial ultrasonography through sonolucent cranioplasty


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: transcranial ultrasonography through sonolucent cranioplasty<br>All surgical procedures and implants in this protocol are standard of care. | Device: ClearFit implant<br>* 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.<br>Procedure: transcranial ultrasonography through sonolucent cranioplasty<br>* 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.<br>* 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 | 
| 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 | 
| 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 |