Managing Non-acute Subdural Hematoma Using Liquid Materials：a Chinese Randomized Trial of MMA Treatment
Phase: NA
Conditions: Subdural Hematoma, Non-acute
Sponsor: Huashan Hospital

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Managing non-acute subdural hematoma using liquid materials: 
a Chinese randomized trial of middle meningeal artery treatment 
(MAGIC-MT)—protocol 
Study No.: 
MAGIC-MT 
Study Protocol Version No.: 
V3.0 
Study Protocol Version Date: 
21 Sept 2022 
Coordinating Investigators: 
Professor Mao Ying 
Huashan Hospital, Fudan University 
No. 433 Huashan Road, Jing'an District, Shanghai 
200040 
Professor Liu Jianmin 
First Affiliated Hospital of the Second Military Medical 
University (Changhai Hospital of Shanghai) 
No. 168 Changhai Road, Yangpu District, Shanghai 
200082 
Sponsor: 
Huashan Hospital, Fudan University 
First Affiliated Hospital of the Second Military Medical 
University (Changhai Hospital of Shanghai) 

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Protocol Signature Page 
 
Sponsor: 
Signature 
Date 
 
Huashan Hospital, Fudan 
University 
 
 
 
 
First Affiliated Hospital of the 
Second Military Medical 
University (Changhai Hospital of 
Shanghai) 
 
 
 
 
 
I have carefully read this trial protocol, and I agree that this protocol covers all the necessary 
contents required for the implementation of the trial. I will conduct the study according to the 
study protocol and complete the study within the specified time. 
I will provide copies of this study protocol and all relevant materials to all personnel assisting 
me in this study. I will discuss these materials with them to ensure that they fully understand 
the relevant investigational products and how to conduct the trial. 
 
Name 
Signature 
Date 
[Principal Investigator]: 
 
 
 
 
 

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Study Protocol Synopsis 
Study Title 
Managing non acute subdural hematoma using liquid materials: a Chinese randomized 
trial of middle meningeal artery treatment (MAGIC-MT) 
Study 
Objectives 
Primary objective: 
To validate that middle meningeal artery (MMA) embolization with liquid embolic 
materials, when compared to conventional treatments, can reduce the incidence of 
hematoma recurrence in patients receiving trepanation and drainage and the incidence 
of hematoma progression in patients undergoing conservative treatment in 
symptomatic non-acute subdural hematoma (SDH) patients. 
Secondary objectives: 
a. 
To validate the safety and efficacy of MMA embolization with liquid embolic 
materials; 
b. 
To assess change in residual hematoma size at 90 days post-procedure in patients 
undergoing MMA embolization; 
c. 
To assess improvement in clinical outcome (modified Rankin Scale [mRS] score) 
at 90 days and 360 days post-procedure in patients undergoing MMA 
embolization; 
d. 
To assess improvement in health status (EQ-5D scale) at 90 days and 360 days 
post-procedure in patients undergoing MMA embolization; 
e. 
To assess the readmission rate within 90 days post-procedure in patients 
undergoing MMA embolization. 
Study Design 
Multicenter phase III prospective randomized controlled trial with open-label 
treatment and blinded outcome assessment 
Number of 
Study Sites 
30-40 domestic hospitals 
Statistical 
Considerations 
and Sample 
Size 
Assuming that the incidence of events in the traditional treatment group is 12% and 
the embolization group is 5%, with a power of 90% and an estimated 8% drop-out rate, 
approximately 722 subjects should be enrolled with a ratio of 1:1 between the 
embolization group and the traditional treatment groups. 
Inclusion 
Criteria 
1. 
Patients with symptomatic non-acute SDH with mass effect (i.e., chronic or 
subacute SDH) 
Mass effect refers to a shift in midline structure or deformation of local cerebral 
cortex due to SDH. 
Symptomatic defined as neurological symptoms, such as headache, short-term 
cognitive dysfunction, language disorder or aphasia, gait instability, decreased 
muscle strength, sensory disturbances, epileptic seizure, etc. 
2. 
Age ≥ 18 years; 
3. 
Pre-morbid mRS score ≤ 2; 
4. 
Informed Consent Form (ICF) signed by patient or guardian. 
Exclusion 
Criteria 
1. 
Radiographic imaging indicating massive cerebral infarction with corresponding 
symptoms; 
2. 
Required craniotomy or craniotomy with small bone flap to remove SDH; 
3. 
Emergency SDH removal/drainage; 
4. 
Bilateral SDH with unknown origin of symptoms; 

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5. 
Anatomical variations that may affect the safety of MMA embolization (e.g., 
prominent middle MMA-ophthalmic artery anastomosis); 
6. 
Intractable coagulation dysfunction or abnormal platelet count and function (pre-
operative International Normalized Ratio [INR] > 1.5 and/or platelet count < 
80×10 9/L); 
7. 
Contraindications to cerebral angiography, such as allergy to iodinated contrast 
agents, renal insufficiency (GFR < 30 ml/min), etc.; 
8. 
Computed tomography (CT) or magnetic resonance imaging (MRI) showing 
intracranial space-occupying lesions; 
9. 
Pregnancy or planning to become pregnant; 
10. Serious or fatal coexisting disease that may prevent improvement of conditions 
or completion of follow-up; 
11. Life expectancy < 1 year; 
12. Recent operation unrelated to this study or investigators believe that they will be 
at higher risks if antiplatelet and/or anticoagulant drugs are discontinued; 
13. Inability to complete follow-up as required by the protocol; 
14. Patients participating in other clinical trials; 
15. Prior surgery or interventional therapy on target SDH; 
16. Inability to complete MMA embolization before trepanation and drainage. 
Treatment 
Assignment 
Eligible subjects will be randomly assigned to the traditional treatment group or MMA 
embolization group at a ratio of 1:1. 
Primary 
Efficacy 
Endpoints 
Symptomatic SDH recurrence and progression rate within 90 days post-procedure. 
Symptomatic SDH recurrence refers to the maximum thickness of hematoma 
exceeding 10 mm combined with neurological symptoms, or the patient requires re-
operation (surgery group); 
Symptomatic SDH progression refers to the maximum thickness of hematoma 
increasing by more than 3 mm compared with baseline, or the patient requires 
operation (drug therapy group). 
Secondary 
Endpoints 
1. 
Efficacy Endpoints 
• 
Symptomatic SDH recurrence and progression rate at 360 days post-
procedure 
• 
Success rate of target vessel embolization (MMA trunk and branch vessels) 
on digital subtraction angiography (DSA) imaging 
• 
Change in hematoma thickness on CT/MRI at 90 days post-procedure 
• 
Change in hematoma volume at 90 days post-procedure 
• 
Change in midline shift on CT/MRI at 90 days post-procedure 
• 
Change in mRS score at 90 days and 360 days post-procedure 
• 
Proportion of patients with mRS score ≤ 2 at 90 days and 360 days post-
procedure 
• 
Proportion of patients with mRS score ≤ 3 at 90 days and 360 days post-
procedure 
• 
Quality of life evaluated with EQ-5D Scale at 90 days and 360 days post-
procedure 
• 
Total hospital length of stay, number of re-hospitalizations, discharge 

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location, and total hospitalization expenses 
2. 
Safety Endpoints 
• 
Serious Adverse Events (SAEs) within 90 days and 360 days; 
• 
SDH-related mortality within 90 days and 360 days; 
• 
Severe surgery-related complications within 30 days post-procedure 
(including surgery and intervention) 
o 
Symptomatic intracranial hemorrhage 
o 
Surgery-related intracranial hemorrhage 
o 
Surgery-related neurological deficits 
o 
Surgery-related central nervous system infection 
o 
Surgery-related arterial dissection, vascular wall injury, or vascular 
rupture and perforation 
o 
Surgery-related ischemia 
o 
Retroperitoneal/wrist hematoma 
o 
Neuropathy at the puncture site 
o 
Contrast allergy or contrast encephalopathy 
Randomization 
Subjects will be randomized into the control group or the study group using a stratified 
randomization method using SAS (version 9.4 or updated) to generate the 
randomization list. 
 

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Table of Contents 
 
Study Protocol Synopsis .......................................................................................................... 42 
List of Abbreviations ............................................................................................................... 47 
1. 
Introduction ...................................................................................................................... 49 
2. 
Clinical Study Objectives and Endpoints ........................................................................ 51 
3. 
Study Design .................................................................................................................... 53 
3.1 
Overall Study Design ............................................................................................... 53 
3.2 
Study Duration ......................................................................................................... 54 
4. 
Study Population .............................................................................................................. 54 
5. 
Treatment in the Study ..................................................................................................... 56 
5.1 
Best Medical Care .................................................................................................... 56 
5.2 
Burr-hole drainage ................................................................................................... 57 
5.3 
MMA Embolization ................................................................................................. 57 
6. 
Study Process ................................................................................................................... 58 
6.1 
Study Flowchart ....................................................................................................... 58 
6.2 
Informed Consent and Enrollment ........................................................................... 58 
6.3 
Medical History and Vital Signs .............................................................................. 58 
6.4 
Randomization ......................................................................................................... 59 
6.5 
Clinical Examination and Evaluation ...................................................................... 59 
7. 
Statistical Analysis ........................................................................................................... 60 
7.1 
General Principle ..................................................................................................... 60 
7.2 
Safety Analysis ........................................................................................................ 62 
7.3 
Efficacy Analysis ..................................................................................................... 62 
8. 
Data Management ............................................................................................................ 65 
8.1 
Filing of Case Report Form ..................................................................................... 65 
8.2 
Data Verification and Query .................................................................................... 65 
8.3 
Database Locking..................................................................................................... 65 
9. 
Ethical Protection and Informed Consent of Clinical Study ............................................ 65 
9.1 
Ethical Considerations ............................................................................................. 65 
9.2 
Approval of Study Protocol ..................................................................................... 66 
9.3 
Informed Consent Process and Informed Consent Form ......................................... 66 
10. 
Provisions on Aes ........................................................................................................ 66 
10.1 
Adverse Events ........................................................................................................ 66 
10.2 
SAEs ........................................................................................................................ 68 
10.3 
Possible Adverse Events and Plans.......................................................................... 68 
11. 
Management Considerations ........................................................................................ 68 
12. 
Confidentiality Principle .............................................................................................. 71 
13. 
Agreement on the Publication of Study Results .......................................................... 71 

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14. 
References .................................................................................................................... 72 
Appendix 1. 
Study Flowchart ............................................................................................... 75 
Appendix 2. 
EQ-5D Scale .................................................................................................... 76 
Appendix 3. 
Modified Rankin Scale (mRS score) ............................................................... 78 
 

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List of Abbreviations 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AVM 
Arteriovenous Malformation 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CEC 
Clinical Event Committee 
CMH 
Cochran-Mantel-Haenszel 
Cr 
Creatinine 
CRC 
Clinical Research Coordinator 
CRF 
Case Report Form 
CSDH 
Chronic Subdural Hematoma 
CT 
Computed Tomography 
CTA 
Computerized Tomographic Angiography 
DBP 
Diastolic Blood Pressure 
DSA 
Digital Subtraction Angiography 
DSMB 
Data and Safety Monitoring Board 
OAC 
Outcome Assessment Committee 
eCRF 
Electronic Case Report form 
EC 
Ethics Committees 
EDC 
Electronic Data Capture System 
EQ-5D 
A standardized assessment instrument (developed by the EuroQol Group) that 
provides a simple descriptive measure of health outcome   
g/L 
Grams per Liter 
GCS 
Glasgow Coma Scale score 
HCG 
Human Chorionic Gonadotropin 
IA 
Intra-arterial 
IAC 
Imaging Assessment Committee 
IC 
Informed Consent 
ICH 
Intracranial Hemorrhage 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ICA 
Internal Carotid Artery 
IV 
Intravenous 
KM 
Kaplan Meier 
MCA 
Middle Cerebral Artery 
MGS 
Modified Graeb Scale score 
MMA 
Middle Meningeal Artery 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 

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NBCA 
n-butyl-cyanoacrylate 
NCCT 
Non-Contrast CT Scan 
PI 
Principal Investigator 
RCT 
Randomized Controlled Trial 
REB 
Research Ethics Board  
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
SAH 
Subarachnoid Hemorrhage 
SAP 
Statistical Analysis Plan 
SDH 
Subdural Hematoma 
SOP 
Standard Operating Procedure 

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1. Introduction 
Chronic subdural hematoma (CSDH), representing around 10% of intracranial hematomas, is 
a prevalent form of traumatic brain injury, with an annual incidence rate of 3─5.4 per 100,000 
patients. The rise in craniocerebral trauma, particularly among the elderly, alongside increased 
use of antiplatelet and anticoagulant therapies, has amplified the risk of non-acute SDH, 
thereby intensifying the health challenges in this demographic.1-3. Current treatment methods 
for CSDH include conservative drug treatment, trepanation and drainage, and hematoma 
removal by craniotomy. Although treatment modalities like conservative pharmacotherapy, 
trepanation with drainage, and craniotomy for hematoma evacuation exist, the intricate 
pathophysiology of CSDH often obscures the bleeding source, complicating effective 
management. With recurrence rates ranging from 2 to 37%, the urgency for a safe, efficacious 
CSDH treatment protocol is paramount to decrease these rates and improve patient outcomes.4-
6. 
The pathogenesis and resolution of CSDH remain partially understood. Research suggests its 
association with factors such as bridging vein laceration, osmotic pressure variations, 
hemorrhaging within the hematoma capsule, and localized hyperfibrinolysis. 7. Additionally, 
recent insights highlight the significant role of inflammatory cells in the development and 
progression of subdural hematomas.8,9. In clinical practice, pharmacological interventions 
targeting inflammation, vascular leakage, and hematoma resolution are employed, with low-
dose atorvastatin and dexamethasone being prevalent. A notable Chinese RCT indicated that 
low-dose atorvastatin (20 mg/day) over an 8-week course significantly enhances hematoma 
absorption and symptom improvement.10 Despite these advancements, the complete efficacy 
and safety profiles of such treatments remain under exploration, as a significant patient cohort 
experiences hematoma progression post-medication, necessitating trepanation and drainage. 
Moreover, the recurrence rate for non-acute SDH post these procedures remains considerably 
high. 
Current understanding suggests that the genesis and progression of CSDH predominantly 
involves the formation of an inflammatory pseudomembrane following subdural bleeding. This 
pseudomembrane's outer layer tightly adheres to the dura mater, incorporating newly formed, 
fragile vessels with heightened permeability. These vessels are susceptible to recurrent 
bleeding and leakage, potentially exacerbating hematoma growth and post-surgical recurrence. 
Notably, Tanaka et al.11’s selective angiography of the middle meningeal artery (MMA) in 

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CSDH patients revealed diffuse dilation and abnormal vascular networks, possibly representing 
large capillaries of the hematoma's adventitia. Histological examinations further identified 
diverse vascular structures (capillary-like vessels, venules, arterioles) penetrating the dura 
mater and connecting with MMA branches, underscoring the MMA's pivotal role in the blood 
supply to CSDH pseudomembranes and its significance in hematoma evolution. 
MMA embolization, primarily utilized for treating dural arteriovenous fistulas and 
arteriovenous malformations, has emerged as a pivotal intervention in CSDH management. By 
obstructing the blood supply to the hematoma's adventitia, MMA embolization effectively 
mitigates the enlargement and recurrence of CSDH. Conventional treatments often report high 
recurrence and progression rates, particularly in patients on long-term antiplatelet or 
anticoagulant therapy. In cases of recurrent and refractory CSDH, MMA embolization has 
demonstrated significant efficacy in reducing hematoma progression and recurrence.13,14 15-17. 
Initially reported by Mandai in 2000, this technique gained prominence following its successful 
application in a patient with coagulation dysfunction and recurrent CSDH post multiple 
trepanations.18 Neurosurgeons increasingly adopt MMA embolization for refractory CSDH, 
enhancing brain recovery, minimizing recurrence, and improving overall prognosis. Recent 
trends in endovascular treatment have positioned MMA embolization as a focal strategy in 
CSDH therapy. Systematic reviews indicate a mere 4.1% recurrence rate post-MMA 
embolization in newly diagnosed CSDH cases, highlighting its potential in mild cases to 
obviate surgical intervention19. Clinical studies also suggest that combining MMA 
embolization with traditional drainage can augment CSDH absorption rates, further lowering 
recurrence.20 A 2019 meta-analysis reported significantly lower recurrence rates post-MMA 
embolization (2.1%) compared to traditional surgery (27.7%), underscoring its effectiveness in 
CSDH treatment1. 
Both liquid and solid embolics are employed in MMA embolization. Liquid options include 
Onyx and n-butyl-cyanoacrylate (NBCA) glues, whereas solid materials comprise coils, 
polyvinyl alcohol (PVA) particles, and gelatin sponge particles. For CSDH, solid embolics 
have been favored, as their size exceeds that of the MMA's risky anastomotic vessels (~100 
μm), enhancing safety. Conversely, liquid embolics, by filling and effectively sealing target 
vessels, minimize recanalization risks and heighten permanent occlusion rates. Given their 
precise targeting and superior embolization capabilities, liquid embolics, particularly for 
cerebrovascular malformations, have gained preference over solids, which now often serve as 
adjuncts. Yet, in non-acute SDH treatments using liquid embolics, such as Onyx, reports 

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remain sparse and warrant further large-scale clinical studies for robust evidence. 
Onyx™ Liquid Embolic System, a leading liquid embolic, comprises an ethylene-vinyl alcohol 
(EVOH) copolymer, dimethyl sulfoxide (DMSO) solvent, and micronized tantalum powder. 
Its non-adhesive nature prevents microcatheter and vessel adhesion, facilitating safer post-
embolization catheter retraction. Each application of Onyx™ propels preceding agents deeper 
into smaller vessels beyond microcatheter reach, enhancing dispersal. Onyx™ received CE 
certification in Europe in 1999 and was initially approved for cerebral AVM endovascular 
embolization. Notably, Rajah et al.'s case series utilizing Onyx for MMA embolization via the 
radial artery pathway underscored its safety and efficacy in CSDH treatment.21  
Although various studies endorse MMA embolization as an effective treatment for CSDH, 
most are confined to single-center, prospective cohort designs with diverse patient inclusion 
criteria and intervention approaches. There's a notable gap in high-level evidence validating 
MMA embolization's efficacy. The MAGIC-MT study aims to bridge this gap by rigorously 
assessing the efficacy and safety of MMA embolization in comparison to conventional CSDH 
treatments. Furthermore, it seeks to contribute significantly to the standardization of clinical 
treatment protocols for CSDH. 
2. Clinical Study Objectives and Endpoints 
Primary objective: 
To validate that MMA embolization with liquid embolic materials, when compared to 
conventional treatments, can reduce the incidence of hematoma recurrence in patients receiving 
trepanation and drainage and the incidence of hematoma progression in patients undergoing 
conservative treatment in symptomatic non-acute SDH patients. 
Secondary objectives: 
a. To validate the safety and efficacy of MMA embolization with liquid embolic materials; 
b. To validate a reduction in residual hematoma size at 90 days post-procedure in patients 
undergoing MMA embolization; 
c. To validate improvement in clinical outcome (modified Rankin Scale [mRS] score) at 90 
days and 360 days post-procedure in patients undergoing MMA embolization; 

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d. To validate improvement in health status (EQ-5D scale) at 90 days and 360 days post-
procedure in patients undergoing MMA embolization; 
e. To validate a reduced readmission rate within 90 days post-procedure in patients 
undergoing MMA embolization. 
The efficacy endpoints in this study include: 
Primary efficacy endpoint: 
• 
Symptomatic SDH recurrence and progression rate within 90 days post-procedure 
Symptomatic SDH recurrence refers to the maximum thickness of hematoma 
exceeding 10 mm combined with neurological symptoms, or the patient requires re-
operation (surgery group); 
Symptomatic SDH progression refers to the maximum thickness of hematoma 
increasing by more than 3 mm compared with baseline, or the patient requires 
operation (drug therapy group). 
Secondary efficacy endpoints: 
• Symptomatic SDH recurrence and progression rate at 360 days post-procedure 
• Success rate of target vessel embolization (MMA trunk and branch vessels) on digital 
subtraction angiography (DSA) imaging 
• Change in hematoma thickness on computed tomography (CT)/magnetic resonance 
imaging (MRI) at 90 days post-procedure 
• Change in hematoma volume at 90 days post-procedure 
• Change in midline shift on CT/MRI imaging at 90 days post-procedure 
• Change in mRS score at 90 days and 360 days post-procedure 
• Proportion of patients with mRS score ≤ 2 at 90 days and 360 days post-procedure 
• Proportion of patients with mRS score ≤ 3 at 90 days and 360 days post-procedure 
• Quality of life evaluated with EQ-5D Scale at 90 days and 360 days post-procedure 

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• Total hospital length of stay, number of re-hospitalizations, discharge location (home 
vs. rehabilitation hospital), and total hospitalization expenses 
The safety endpoints in this study include: 
• Serious adverse events (SAEs) within 90 days and 360 days; 
• SDH-related mortality within 90 days and 360 days; 
• Severe surgery-related complications within 30 days post-procedure (including surgery 
and embolization) 
o Symptomatic intracranial hemorrhage 
o Surgery-related intracranial hemorrhage 
o Surgery-related neurological deficits 
o Surgery-related central nervous system infection 
o Surgery-related arterial dissection, vascular wall injury, and vascular rupture and 
perforation 
o Surgery-related ischemia 
o Retroperitoneal/wrist hematoma 
o Neuropathy at the puncture site 
o Contrast allergy or contrast encephalopathy 
Note: Follow-up time at 30 days, 90 days, and 360 days post-procedure will be calculated based 
on the day of randomization in this study. Relevant endpoint events and safety events will be 
collected at these follow ups. 
3. Study Design 
3.1 Overall Study Design 
This is a multicenter, phase III, prospective, randomized, open-label, and parallel controlled 
clinical study with blinded outcome assessment. Approximately 722 cases will be included in 
this study in China, with a ratio of 1:1 for randomization into the MMA embolization and 

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traditional treatment groups. 
The study phases include: 1) Screening and baseline period: confirm whether patients are 
eligible for the study and create a record; decide whether trepanation and drainage should be 
performed by considering the condition of the disease and the imaging results; carry out 
randomized assignment and therapy. Eligible subjects will be randomly assigned to the 
traditional treatment group or MMA embolization group at a ratio of 1:1. 2) Follow-up period: 
visit patients for efficacy endpoints and safety endpoints at 30 days, 90 days, and 360 days 
post-procedure. 
Figure 1. Schematic diagram of inclusion and randomization of subjects 
 
3.2 Study Duration 
In MAGIC-MT, the estimated enrollment time will be from January 2021 to June 2023, for a 
span of 30 months from the first to the last enrollment of subjects. After the completion of 
enrollment, the last subject will be followed up for 360 days post-procedure. 
4. Study Population 
4.1 
Subjects must meet all the following inclusion criteria before they can participate in 
this study: 
(1) Patients with symptomatic non-acute SDH with mass effect (i.e., chronic or subacute 
SDH); 

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Mass effect refers to a shift in midline structure or deformation of local cerebral cortex 
due to SDH. 
Symptomatic defined as neurological symptoms, such as headache, short-term 
cognitive dysfunction, language disorder or aphasia, gait instability, decreased muscle 
strength, sensory disturbances, epileptic seizure, etc. 
(2) Age ≥ 18 years; 
(3) Pre-morbid mRS score ≤ 2; 
(4) Informed Consent Form (ICF) signed by patient or his/her guardian. 
4.2 
Subjects who meet any of the following exclusion criteria are not eligible to 
participate in this study: 
(1) Radiographic imaging indicating massive cerebral infarction with corresponding 
symptoms; 
(2) Required craniotomy or craniotomy with small bone flap to remove SDH; 
(3) Emergency SDH removal; 
(4) Bilateral SDH with unknown origin of symptoms; 
(5) Anatomical variations that may affect the safety of MMA embolization (e.g., 
prominent MMA - ophthalmic artery anastomosis); 
(6) Intractable coagulation dysfunction or abnormal platelet count and function (pre-
operative International Normalized Ratio [INR] > 1.5 and/or platelet count < 
80×10 9/L); 
(7) Contraindications to cerebral angiography, such as allergy to iodinated contrast agents, 
renal insufficiency (GFR < 30 ml/min), etc.; 
(8) CT or MRI showing intracranial space-occupying lesions; 
(9) Pregnancy or planning to become pregnant; 
(10) Serious coexisting disease that may prevent improvement of conditions or completion 
of follow-up; 

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(11) Life expectancy < 1 year; 
(12) Recent operation unrelated to this study or investigators believe that patient will be at 
higher risks if antiplatelet and/or anticoagulant drugs are discontinued; 
(13) Inability to complete the follow-up as required by the protocol; 
(14) Patients participating in other clinical trials; 
(15) Prior surgery or interventional therapy on target SDH; 
(16) Inability to complete MMA embolization before trepanation and drainage. 
5. Treatment in the Study 
In this study, patients were stratified based on initial clinical assessments into two primary 
categories: those designated for burr-hole drainage and those selected for conservative 
treatment. Each category was then subject to further randomization. Specifically, within the 
burr-hole drainage category, patients were allocated into either the 'burr-hole drainage + 
optimal medical care + MMA embolization' subgroup or the 'burr-hole drainage + optimal 
medical care' subgroup. Similarly, patients initially slated for conservative treatment were 
randomized into 'conservative management + optimal medical care + MMA embolization' and 
'conservative management + optimal medical care' subgroups. 
5.1 
Best Medical Care 
Optimal medical care in this context is tailored to alleviate symptoms and facilitate hematoma 
absorption, utilizing medications such as statins, steroids, and anti-epileptic drugs. The criteria 
for administering optimal medical care include: 1) a confirmed diagnosis of non-acute SDH; 2) 
patients presenting with multiple organ failure or coagulation dysfunction, who are unsuitable 
for or decline surgical intervention; and 3) as a preventative measure against post-operative 
recurrence. Contraindications for these medications encompass allergic reactions to the 
prescribed drugs or other relevant usage restrictions. 
The protocol recommends Atorvastatin calcium and dexamethasone for pharmacotherapy, with 
a low-dose, prolonged regimen of Atorvastatin calcium potentially combined with 
dexamethasone. However, due to the heightened risk of embolic diseases associated with 
hemostatic drugs, their usage is generally discouraged. Ultimately, the specific treatment 

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approach is determined by the attending physician. 
5.2 
Burr-hole drainage 
In this study, 'burr-hole drainage' encompasses the process of trepanation and drainage, which 
is conducted under local anesthesia with analgesia or under general anesthesia. The criteria for 
opting for trepanation and drainage include: (1) clinical manifestations of elevated intracranial 
pressure, potentially accompanied by altered consciousness and signs of cerebral hemisphere 
compression; (2) CT or MRI evidence of unilateral or bilateral SDH with a thickness exceeding 
10 mm and a midline shift greater than 10 mm due to unilateral hematoma; (3) insufficient 
response to prolonged pharmacotherapy aimed at hematoma absorption (exceeding 2 weeks), 
with persistent clinical symptoms, imaging evidence of hematoma growth, intolerability to 
medication, or a recommendation for surgical intervention. Detailed protocols for perioperative 
assessment, surgical procedure, medication, and management of unique clinical situations are 
aligned with the established clinical pathway for CSDH. 
In scenarios where participants in the embolization group necessitate surgical intervention, the 
protocol dictates that embolization precedes trepanation and drainage. 
5.3 
MMA Embolization 
Participants allocated to the MMA embolization group will undergo cerebrovascular 
angiography followed by ipsilateral MMA embolization to address the SDH. Anesthesia, either 
general or monitored local, will be administered as per the procedural needs. The use of 
intravenous heparin during the procedure will be meticulously documented. Initially, femoral 
or radial artery access is established, followed by digital subtraction angiography (DSA) using 
a standard 5 French diagnostic catheter for cerebrovascular evaluation. Subsequently, a guiding 
catheter is positioned in the proximal external carotid artery, and a microcatheter is advanced 
into the main trunk of the MMA under roadmap guidance. Superselective angiography of the 
MMA is then performed to identify any hazardous collateral vessels, such as ophthalmic and 
petrous branches, prior to embolization. Absence of dangerous collaterals allows for 
embolization using ONYX-18 (Medtronic, USA) under blank fluoroscopic roadmap. 
Successful embolization is achieved when both frontal and parietal branches or the main trunk 
of MMA are selectively occluded. For comprehensive embolization, it is advised that the 
microcatheter navigates distally within the frontal and parietal branches, facilitating maximum 
penetration of embolic materials into the smaller vessels. In this trial, MMA embolization is 

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recommended to precede burr-hole drainage in patients assigned to the combined treatment 
group. 
6. Study Process 
This clinical study focuses on assessing the effectiveness of Middle Meningeal Artery (MMA) 
embolization in treating Chronic Subdural Hematoma (CSDH). It includes a detailed flowchart 
for the study process (Appendix 1), encompassing informed consent, enrollment, and various 
stages of evaluation. Key aspects involve obtaining written informed consent, medical history 
recording, vital signs monitoring, and a stringent randomization process using SAS software. 
The study also emphasizes comprehensive clinical examinations and evaluations, including 
routine blood tests, imaging (CT/MRI), and scoring assessments (mRS, EQ-5D) at multiple 
stages. Additionally, the study records hospitalization details, re-hospitalization rates, and 
surgery-related complications to ascertain the treatment’s effectiveness and safety. 
6.1 
Study Flowchart 
See Appendix 1. 
6.2 
Informed Consent and Enrollment 
Subjects will be requested to provide written informed consent (IC) after receiving the study 
information. The investigators will explain the materials according to the requirements of 
subjects. Every subject (or his/her legal representative) and investigator must sign and date the 
IC form (ICF) approved by the Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) before the subject can proceed with the qualification screening. Copies of the ICF 
will be provided to all subjects. Subjects who provide written IC will be screened and evaluated. 
Subjects who do not provide IC will receive further treatment according to the doctor's advice 
and/or the subject's willingness. 
After obtaining IC from subjects, the investigators shall screen them according to the inclusion 
and exclusion criteria, confirming that subjects do not fall under any of the exclusion criteria. 
Only when a subject meets all inclusion criteria and does not meet any exclusion criteria can 
the investigators assign the subject into a group according to the random assignment instruction. 
6.3 
Medical History and Vital Signs 
During the screening visit, the medical history of the subjects will be collected and recorded in 

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the eCRF. Baseline measurements, including blood pressure and heart rate, will be taken. 
6.4 
Randomization 
The assignment for each subject into either the control group (no MMA embolization) or the 
study group (MMA embolization) will be determined by the randomization scheme. SAS 
(version 9.4 or updated) is used to generate the randomization list by a stratified randomization 
method. During screening, a unique identification number (screening number) is allocated to 
each subject who has provided the signed ICF. The annotation for the screening number 
includes a subject number and site number (e.g., the first subject in 01 site is 01001). This 
digital ID is allocated according to the order of entry into the study after the subject signs the 
ICF at the study site. 
On day 0 of the trial, subjects obtain the corresponding randomization numbers and will be 
randomized to the study group or the control group at a ratio of 1:1. 
The randomization number of subjects in all study groups is designated as #: D-ZZZ 
D = representing the treatment group; expressed with Arabic numerals 1-X, where 1 represents 
the study group and 2 represents the control group. 
ZZZ=Subject digital ID 
Treatment allocation in this study is not blinded. 
6.5 
Clinical Examination and Evaluation 
(1) Inspection items before randomization include: 
Routine blood work (red blood cell count, white blood cell count, platelet count, and 
hemoglobin); 
Coagulation (activated partial thromboplastin time [APTT], INR); 
Hepatic and renal function (alanine aminotransferase [ALT], aspartate aminotransferase 
[AST], blood urea nitrogen [BUN], creatinine [Cr]), electrolytes (potassium, sodium, 
chlorine, and fingerstick blood glucose); 
Cranial CT scanning; 

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DSA; 
Cranial MRI (depending on the conditions); 
Urine human chorionic gonadotropin (HCG) test (female of childbearing age). 
(2) Assess mRS score and EQ-5D score at screening and during baseline period; 
(3) Total length of hospital stay, destination for rehabilitation after discharge, and total 
hospitalization expenses are recorded at discharge; 
(4) Record severe surgery-related complications of subjects in 30 days after any surgical 
procedure (including burr-hole drainage and MMA embolization); 
(5) Re-examine cranial CT/MRI at 90 days after randomization and record total hospital stay, 
re-hospitalization times, destination for rehabilitation after discharge, and total 
hospitalization expenses; 
(6) Assess mRS score and EQ-5D score at 90 days and 360 days after randomization; 
(7) Record SAEs, SDH-related death events, and severe surgery-related complications, total 
hospital length of stay, number of re-hospitalizations, destination for rehabilitation after 
discharge, and total hospitalization expenses at 30 days, 90 days and 360 days after 
randomization. 
7. Statistical Analysis 
7.1 
General Principle 
A biostatistician will develop a statistical analysis plan according to the study protocol before 
data locking. 
Continuous variables are expressed as mean ± standard deviation, with the number of cases, 
median, maximum, and minimum provided; categorical variables are described by frequency 
and constituent ratio. 
7.1.1 
Test level 
Two-sided tests are performed for all hypothesis tests (α = 0.05). The confidence level of all 
confidence intervals is 95%. 

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7.1.2 
Hypothesis test 
Original hypothesis: there is no difference in the incidence of recurrence or progression of 
hematoma between the MMA embolization group and the traditional treatment group at 90 
days post-procedure; 
Alternative hypothesis: there is a difference in the incidence of recurrence or progression of 
hematoma between the MMA embolization group and the traditional treatment group at 90 
days post-procedure. 
7.1.3 
Estimation of sample size 
This study hypothesizes that MMA embolization may reduce the recurrence (operation group) 
or progression (conservative treatment group) of SDH. The estimated recurrence or progression 
rate of hematoma in the MMA embolization group is 5%, while that of control group is 12%. 
When estimating bilateral 5% for the statistical significance level, 90% for power, and 8% for 
an acceptable rate of loss to follow-up, the total sample size is estimated to be 722 cases. 
7.1.4 
Estimation of missing values 
Missing values are not imputed. 
7.1.5 
Subject disposition 
Description of subjects' enrollment, drop-out cases, completion of expected follow-up, and 
early suspension presented as the number of cases and percentage;  
Subject disposition by data set. 
Descriptions for drop-out subjects are individually described, including treatment condition, 
reason for premature withdrawal from the trial, etc. 
7.1.6 
Protocol violation and deviation 
Summarize and describe the subjects with protocol violations and deviations. 
7.1.7 
Demographics and baseline characteristics 
Age, height, weight, vital signs, and other baseline characteristics are described by mean, 
standard deviation, median, maximum, and minimum; the constituent ratio is calculated for 

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gender, smoking status, drinking status, medical history, drug allergy history, physical 
examination, etc. 
7.2 
Safety Analysis 
7.2.1 
Adverse events 
Adverse event (AE) data is described according to the current version of MedDRA and then 
statistically analyzed. 
SAEs within 90 days and 360 days post-procedure and the incidence of serious surgery-related 
complications within 30 days after surgery are summarized. The incidence of AEs is recorded 
as 1 case if multiple AEs occur in one patient or the same AE occurs frequently in one patient. 
AEs will be summarized by system organ class (SOC) and preferred term (PT) in a frequency 
table. The incidence is calculated by systems and symptoms/signs (count of cases: the number 
of subjects with at least one AE). 
Severity of AEs: When the same subject has the same AE several times, the most serious one 
is used to analyze the severity of the AE. 
A list of subjects experiencing AEs will be provided. 
7.2.2 
Death 
Mortality within 90 days and 360 days post-procedure is summarized, and a list of cases is 
provided. 
7.2.3 
Concomitant medication (during the study) 
Summarize the usage of concomitant medication during the study (including any changes in 
concomitant medication during screening, new concomitant medication after screening, and 
drugs for treating AEs), and the frequency of use of each drug. 
7.3 
Efficacy Analysis 
7.3.1 
Primary efficacy analysis 
Summarize the incidence of the primary endpoint event. 
Primary endpoint event: incidence of recurrence (surgery group) or progression (drug therapy 

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group) of SDH within 90 days post-procedure 
Hematoma recurrence refers that the maximum thickness of hematoma exceeding 10 mm, 
combined with neurological symptoms, or the patient needs to undergo re-operation (surgery 
group); 
Symptomatic CSDH progression refers that the maximum thickness of hematoma increasing 
by more than 3 mm compared with baseline, or the patient requires operation (drug therapy 
group). 
Note: The primary endpoint event is considered to have been met for any patient who died 
from any cause within 90 days post-procedure. 
Cochran-Mantel-Haenszel (CMH) chi-square analysis will be used for primary endpoints. The 
difference in event incidence between the two groups and its 95% confidence interval will be 
calculated. The Kaplan-Meier (KM) method is further used to estimate the incidence of primary 
endpoint events and its 95% confidence interval. 
SAS code to be used in CMH analysis is as follows: 
ods output CMH=CMH_out; 
proc freq data=FatComp order=data; 
 
tables Layer*Exposure*Response /CMH ALPHA=0.05; 
 
weight count; 
 
output out=cmh_ci cmh; 
run; 
Sas code to be used for KM estimation is as follows: 
proc lifetest data=TTE alpha=0.05; 
 
time avalm*cnsr(1); 
 
strata /group=trtg; 
 
ods output Quartiles = Quartiles 

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ProductLimitEstimates=Estimates; 
run; 
7.3.2 
Secondary efficacy analyses 
Summarize the following indicators: 
• 
Recurrence or progression rate of SDH at 360 days post-procedure 
• 
Success rate of target blood vessel embolization (MMA trunk and branch vessels) on DSA 
imaging 
• 
Change in hematoma thickness on CT/MRI at 90 days post-procedure 
• 
Change in hematoma volume at 90 days post-procedure 
• 
Change in midline shift on CT/MRI at 90 days post-procedure 
• 
Change in mRS score at 90 days and 360 days post-procedure 
• 
Proportion of patients with mRS ≤ 2 at 90 days and 360 days post-procedure 
• 
Proportion of patients with mRS ≤ 3 at 90 days and 360 days post-procedure 
• 
Quality of life evaluated with EQ-5D Scale  at 90 days and 360 days post-procedure 
• 
Total hospital length of stay, number of re-hospitalizations, destination for rehabilitation 
after discharge (home vs. rehabilitation hospital) and total hospitalization expenses 
Same as primary endpoint analysis, Chi-square test (qualitative indicator) or t-test (quantitative 
indicators) is used for inter-group comparison in secondary endpoint analysis. 
For time event endpoints, such as incidence of recurrence or progression of SDH at 360 days 
post-procedure, the KM method will be used. 
7.3.3 
Sub-Group analysis 
In the evaluation of both primary and secondary outcomes, pre-specified subgroup analyses 
were conducted, focusing on distinctions between patients undergoing burr-hole drainage and 
those receiving optimal medical management. For safety assessments, the analysis 
encompasses all patients who were randomized and subsequently underwent the study 

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treatment. 
8. Data Management 
8.1 
Filing of Case Report Form 
The design of the Case Report Form (CRF) shall guarantee the collection of all data which are 
specified in the study protocol and meet the needs of statistical analysis. Electronic Case Report 
Form (eCRF) is an electronic form of CRF, which is used to record the data of each subject 
during the trial. The eCRFs must be filled in and completed for all included cases. 
Electronic Data Capture System (EDC) for clinical trials is adopted for data collection 
management. The clinical trial investigator or Clinical Research Coordinator (CRC) shall fill 
in the eCRF accurately, timely, completely, and standardly according to CRF filing instructions. 
8.2 
Data Verification and Query 
In order to ensure the integrity, consistency, and accuracy of data, automatic logic verification 
and manual logic verification are adopted. The EDC system performs real-time automatic logic 
verification on the filled data, such as the range and logical relationship of data values. The 
data administrator will send a manual Query in EDC. 
8.3 
Database Locking 
After completing all data filling and query clearing, the PI, statistical analyst, Sponsor 
representative, clinical research associate (CRA) representative, and data administrator 
complete the final definition and judgment of the analysis population, and approve database 
locking in writing, and then the data administrator locks the database. 
Generally, the locked database cannot be unlocked. If unlocking is needed, the unlocking 
conditions and procedures must conform to the corresponding SOP, and the unlocking process 
must be carefully controlled and recorded. 
9. Ethical Protection and Informed Consent of Clinical Study 
9.1 
Ethical Considerations 
The clinical study shall be conducted in compliance with the codes of ethics set forth in the 
Declaration of Helsinki by World Medical Association and Good Clinical Practice for Medical 

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Device Clinical Trials. Before the study begins, the Ethics Committee (EC) shall strictly 
deliberate the study protocol and related documents from the perspective of protecting the 
rights and interests of subjects, and the study can be implemented only after obtaining the 
written approval of the EC. All parties involved in the study shall bear corresponding ethical 
responsibilities according to their respective responsibilities in the study. 
9.2 
Approval of Study Protocol 
Before the clinical study, the investigators need to submit the clinical study protocol, ICF and 
other related documents to the EC of hospitals where the clinical study site is located. The 
clinical study can only be started after approved by the EC. Any amendment to the study 
protocol must be approved by the EC before it can be implemented. 
9.3 
Informed Consent Process and Informed Consent Form 
Before including a subject, the investigator must explain details of the clinical study to the 
subject: 
The subject voluntarily participates in the clinical study and has the right to withdraw from the 
clinical study at any stage; 
The personal data of the subject will be kept confidential. The EC, the drug regulatory authority 
and the implementer may consult the information of the subject, but shall not disclose the 
contents; 
During the clinical study, the medical institution has the obligation to provide the subject with 
information related to the clinical study; 
The subject is informed about the contents, objectives, and possible AEs of this study, and can 
only be included after fully understanding this study and signing the ICF; 
The ICF is jointly signed by the investigator and the subject in duplicate, each copy for each 
party. 
10. Provisions on Aes 
10.1 
Adverse Events 
10.1.1 Definition of AE 

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An AE is defined as any untoward medical occurrence in the process of the clinical study, 
regardless of its relationship to the investigational medical device. 
10.1.2 Classification of adverse events 
Mild: The subject can tolerate, without effecting the treatment. No special treatment is required. 
There is no impact on the health of the subject. 
Moderate: The subject cannot tolerate, with the need of device removal or special treatment. 
There is direct impact on the health of the subject. 
Severe: It endangers a subject’s life, leading to disability or death. Device removal or an 
emergency treatment needs to be done immediately. 
10.1.3 Correlation between Aes and investigational devices 
1) Definitely related: The type of Aes has been confirmed as the type of reaction that must 
occur in investigational medical device, which accords with the reasonable chronological 
order after treatment, and this AE cannot be explained by other reasons. 
2) Probably related: The occurrence of Aes may be caused by the use of investigational 
medical device, and there is a reasonable chronological order between the occurrence of 
events and the use of investigational medical device. 
3) Possibly related: The occurrence of Aes may be caused by the investigational medical 
device, and other factors cannot be ruled out. There is a reasonable chronological order 
between the occurrence of Aes and the use of investigational medical device, and the 
causality between the events and the use of investigational medical device cannot be ruled 
out. 
4) Possibly unrelated: The occurrence of Aes is more likely related to other factors. Or the 
occurrence time of the AE indicates that it is unlikely to have causality with the use of 
investigational medical device. 
5) Not related: There is no correlation between the occurrence of Aes and the use of 
investigational medical device. 
6) Unable to determine: The correlation between the occurrence of Aes and the use of 
investigational medical device cannot be determined. 

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10.2 
SAEs 
SAEs are the following events occurred during the clinical study: 
1) Death; 
2) Fatal disease or injury; 
3) Permanent impairment of a body structure or a body function; 
4) Resulting in hospitalization or prolonged hospitalization; 
5) Medical or operative intervention is required to avoid any permanent impairment in the 
physical structure or physical function; 
6) Fetal distress, fetal death or congenital anomalies, congenital defect, etc. 
10.3 
Possible Adverse Events and Plans 
1) Cerebral vasospasm: during embolization, cerebral vasospasm may be induced due to 
repeated operations and embolization and stimulation of contrast media on the vessel wall. 
Intravenous or transarterial administration of antivasospasm drugs such as Nimotop 
injection, Fasudil injection, and Papaverine injection can be used during the surgery, to 
improve cerebral vasospasm in patients in the embolization group.  
2) Mistaken embolization: because there are communicating branches between intracranial 
and extracranial arteries (dangerous anastomosis), embolic agents are easy to mistakenly 
enter into communicating branches, so it is necessary to master the injection dose and 
speed of embolic agents during embolization to prevent mistaken embolization. 
Circulating nurses shall closely observe the swallowing, pronunciation, vision and limb 
activities of patients, and find out special discomfort symptoms as early as possible. 
3) Contrast agent allergy: although nonionic contrast agents are widely used at present, 
allergic reactions may still occur during endovascular interventional therapy, especially in 
patients with high risk factors of allergy. When the patient is found to have facial flushing, 
nausea, vomiting, headache, blood pressure drop, dyspnea, convulsion, shock and coma, 
allergic reaction shall be considered and anti-allergic treatment shall be given promptly. 
11. Management Considerations 

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Coordinating Investigators: 
Professor Mao Ying 
Huashan Hospital, Fudan University 
No. 433 Huashan Road, Jing’an District, Shanghai 200040 
Professor Liu Jianmin 
First Affiliated Hospital of the Second Military Medical University 
(Changhai Hospital of Shanghai) 
No. 168 Changhai Road, Yangpu District, Shanghai 200082 
Steering Committee 
China: Mao Ying, Liu Jianmin, Gu Yuxiang, Yang Pengfei; 
Foreign country: Mayank Goyal (CAN), Charles Majoie (NED) 
Statistician: 
Professor Zhao Naiqing 
Chairman of Data and Safety 
Monitoring Board (DSMB): 
Prof. Craig Anderson (Aus) 
Contract Research Organization: 
Cardiovascular Chinese Research Center 
11.1 
Subject confidentiality All information, medical records, and laboratory data of 
subjects must be kept confidential. The discussion, analysis and report of information 
and data are only for the purpose of this clinical study. In the eCRF and any report, 
the number will be used to distinguish the subject’s identity, and the subject’s identity 
will be kept confidential. 
11.2 
Study monitoring The Sponsor’s representatives or its designated personnel are 
allowed to visit the study site regularly, to assess the quality of data and the integrity 
of study. The representative will review the study records of the study site and directly 
compare these records with the original documents, discuss the implementation of the 
study with the investigators, and confirm the rationality of study implementation. In 
addition, the study can be evaluated by internal auditors of the Sponsor and 
government inspectors who must be allowed to view eCRFs, original documents, and 
other study documents. The Sponsor’s audit report will be kept confidential. 
During the monitoring visit, the investigator or the designated personnel under the investigator 
must be present at some times to review the data, answer any queries, and be allowed to directly 
access to subject records (such as medical records, office documents, hospital documents, and 
study-related documents) for validation of original data. Before each visit, the eCRF must be 
filled in and provided to the Sponsor’s representative for checking its accuracy and integrity. 
11.3 
CRF and study records: All records will be kept confidential. Personal information 
of subjects, including names, shall not be disclosed at any time. Subjects’ 
clinical/experimental data shall not be disclosed to any party other than the Sponsor 

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or its designated personnel and relevant competent government agencies. In all cases, 
the information must be kept confidential with caution for subjects. In the eCRF and 
other study-related documents, the number will be used to represent the subject’s 
identity. 
The study site staff will collect data electronically. Initially, data will be collected on the 
original documents, and then transcribed to the eCRF. The eCRFs will not be used as the 
primary medium for collecting any data. The data in eCRF is sourced from original documents, 
and must be consistent with original documents. Any deviation between eCRF and original 
documents must be explained and recorded. All necessary information must be recorded in the 
blank space provided in the eCRF. If certain data are not available or not applicable, they must 
be recorded as Not Available or Not Applicable; no blank space can be left. 
Each subject participating in the study must have a complete eCRF, and each page in the form 
must be reviewed and approved by the PI. The PI will confirm that he/she has reviewed the 
recorded data by electronic signature in the electronic data collection page. The PI may entrust 
the review and confirmation to a qualified doctor who may be appointed as an assistant 
investigator. Investigators must keep a copy of the eCRF, including records of changes and 
corrections. 
11.4 
Data and Safety Monitoring Board: An independent Data and Safety Monitoring 
Board (DSMB) will be established to regularly review and analyze all safety data. The 
effect data generated by the study will be evaluated by DSMB for potential risks and 
benefits of the treatment. DSMB will be composed of independent professional 
doctors (at least 2 persons) who will not undertake the recruitment of subjects in this 
study and a biostatistician whose identity is not disclosed. DSMB will keep SAEs 
under review. DSMB will review the frequency and severity of all aEs as well as 
demographic data, etc. Specific meetings may be held for any safety reasons during 
the study. Based on results of data review, if any termination criterion is met, DSMB 
will give suggestions on whether to continue, adjust or terminate the study. Other 
responsibilities and details of DSMB will be included in the DSMB Charter. 
11.5 
Clinical Event Committee (CEC): The CEC will independently and impartially 
evaluate the safety events, including at least all protocol-specified safety endpoints of 
the subjects. The CEC should be composed of at least three independent physicians, 
one of whom will act as CEC President. Details regarding the responsibilities of CEC 

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members and clinical events that require CEC review will be included in the CEC 
constitution. 
11.6 
Imaging assessment committee (IAC): The primary and secondary endpoints of the 
trial involve quantitative imaging assessments, which will be reviewed by the IAC 
with data including at least: CT/MRI (screening period/baseline, 90-day follow up 
[V4], 360-day follow up [V5]), and DSA imaging (target vessels [MMA main and 
branch vessels]). 
11.7 
Outcome Assessment Committee (OAC): The OAC is responsible for evaluation of 
multiple subjective data, including at least clinical symptoms and mRS score (90-day 
follow up [V4] and 360-day follow up [V5]). 
11.8 
Financial disclosure: The financial affairs of the study must be recorded in the 
agreement between the Sponsor and the investigators. 
12. Confidentiality Principle 
The investigator must strictly keep confidential the study results, protocol, and other materials 
and shall not publish any information spontaneously without the written authorization of the 
Sponsor. Any citation must also be made with the Sponsor’s prior written authorization. 
The personal data of the subject participating in the study is confidential; however, the EC, 
National Medical Products Administration (NMPA), competent department of health and 
family planning or the Sponsor may look up the personal data of the subject participating in 
the study for the demand of work according to the established procedure. 
13. Agreement on the Publication of Study Results 
The Sponsor and investigators shall agree on the final study report. 
The study results can be published as scientific literature or submitted to authorities. The 
following terms are made to protect the commercially confidential data. 
All the information about the investigational device (e.g. patent application, the previously 
unpublished manufacturing process and basic scientific data provided by the Sponsor to the 
investigator) is considered confidential and is the property of the Sponsor. The investigator 
shall not use the information for other purposes without the written permission of the Sponsor. 

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Before the study results are published or released, the investigator shall allow the Sponsor to 
review the results and put forward opinions within 30 days to confirm that the confidential 
information is not disclosed and supplement the relevant information. According to the general 
accepted principles of scientific research cooperation, the investigator shall discuss with the 
relevant personnel of Sponsor about the results, and reach an agreement before the publication 
of the results. 
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1. 
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2. 
Link TW, Boddu S, Paine SM, Kamel H, Knopman J. Middle Meningeal Artery 
Embolization for Chronic Subdural Hematoma: A Series of 60 Cases. Neurosurgery 
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3. 
Link TW, Rapoport BI, Paine SM, Kamel H, Knopman J. Middle meningeal artery 
embolization for chronic subdural hematoma: Endovascular technique and radiographic 
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Link TW, Schwarz JT, Paine SM, Kamel H, Knopman J. Middle Meningeal Artery 
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2018;286(3):992-999. 
DOI: 
10.1148/radiol.2017170053. 
21. 
Rajah GB, Waqas M, Dossani RH, et al. Transradial middle meningeal artery 
embolization for chronic subdural hematoma using Onyx: case series. J Neurointerv 
Surg 2020. DOI: 10.1136/neurintsurg-2020-016185. 
22. 
Molyneux AJ, Cekirge S, Saatci I, Gal G. Cerebral Aneurysm Multicenter European 
Onyx (CAMEO) trial: results of a prospective observational study in 20 European 
centers. 
AJNR 
Am 
J 
Neuroradiol 
2004;25(1):39-51. 
(https://www.ncbi.nlm.nih.gov/pubmed/14729527). 
 
 

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Appendix 1. Study Flowchart 
Study procedure 
Screening 
perioda 
Baseline 
Follow-up period 
Visit timeb 
V0 
V1 
V2 
V3 
V4 
V5 
Day -14 to 
Day 0 
Day 0 
Discharge 
Day 30 
Day 90 
Day 360  
Informed consent 
X 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
Inclusion/exclusion 
criteria 
 
X 
 
 
 
 
Medical history and 
previous medication 
X 
 
 
 
 
 
Vital signs 
X 
 
 
X 
X 
X 
Admission 
examinationc 
X 
 
 
 
 
 
CT/MRId 
X 
 
 
 
X 
X 
DSAe 
 
X 
 
 
 
 
Randomization and 
treatment 
 
X 
 
 
 
 
Total hospitalization 
expenses 
 
 
X 
 
X 
X 
Efficacy endpoints 
 
 
 
 
X 
X 
SAEs 
 
 
X 
SDH-related death 
events 
 
 
X 
Severe surgery-
related complications 
 
 
X 
Concomitant 
medication/treatment 
 
 
X 
X 
X 
X 
mRS score 
X 
 
 
 
X 
X 
EQ-5D scale  
X 
 
 
 
X 
X 
a Screening visit and baseline visit can be conducted on the same day 
b The visit time window is ±7 days for V3, ±14 days for V4, and ±30 days  for V5 
c Blood routine (red blood cell count, white blood cell count, platelet count, hemoglobin), coagulation (APTT, 
INR), hepatic and renal function (ALT, AST, BUN, Cr), electrolytes (potassium, sodium, chlorine), random 
blood glucose; urine HCG test is required for female of child-bearing potential 
d CT is mandatory and MRI is optional. The doctor should decide whether MRI is necessary based on the 
condition of the patient 
e This item is conducted only in MMA embolization group 
 

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Appendix 2. EQ-5D Scale 
Your name: 
By placing a tick "√" in one box in each group below, please indicate which statements best 
describe your own health status today. 
Mobility 
I have no problems in walking about (1 point) 
❑ 
I have slight problems in walking about (2 points) 
❑ 
I have moderate problems in walking about (3 points) 
❑ 
I have severe problems in walking about (4 points) 
❑ 
I am unable to walk about (5 points) 
❑ 
Self-care 
I have no problems washing or dressing myself (1 point) 
❑ 
I have slight problems washing or dressing myself (2 points) 
❑ 
I have moderate problems washing or dressing myself (3 points) 
❑ 
I have severe problems washing or dressing myself (4 points) 
❑ 
I am unable to wash or dress myself (5 points) 
❑ 
Usual Activities (e.g., work, study, housework, family or leisure activities) 
I have no problems doing my usual activities (1 point) 
❑ 
I have slight problems doing my usual activities (2 points) 
❑ 
I have moderate problems doing my usual activities (3 points) 
❑ 
I have severe problems doing my usual activities (4 points) 
❑ 
I am unable to do my usual activities (5 point) 
❑ 
Pain /Discomfort 
I have no pain or discomfort (1 point) 
❑ 
I have slight pain or discomfort (2 points) 
❑ 
I have moderate pain or discomfort (3 points) 
❑ 
I have severe pain or discomfort (4 points) 
❑ 
I have extreme pain or discomfort (5 points) 
❑ 
Anxiety or Depression 
I am not anxious or depressed (1 point) 
❑ 

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I am slightly anxious or depressed (2 points) 
❑ 
I am moderately anxious or depressed (3 points) 
❑ 
I am severely anxious or depressed (4 points) 
❑ 
I am extremely anxious or depressed (5 points) 
❑ 
Please mark the point that best represents your health today: 
100 means the best health you can imagine 
0 means the worst health you can imagine 
 
 
 
The best health you 
can imagine 
The worst health 
you can imagine 

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Appendix 3. Modified Rankin Scale (mRS score) 
Patient symptoms 
Score 
No symptoms 
0 
No significant disability despite symptoms; able to carry out all usual works 
and live 
1 
Slight disability, unable to carry out all previous activities, but able to look 
after own affairs without assistance 
2 
Moderate disability; requiring some help, but able to walk without assistance 
3 
Moderately severe disability; unable to walk without assistance and unable to 
attend to own bodily needs without assistance 
4 
Severe disability; bedridden, incontinent and requiring constant nursing care 
and attention 
5