Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Embolic Stroke (INTENSE): a Multicentre, Open-label, Blinded-endpoint, Randomised Controlled Trial
Phase: NA
Conditions: Stroke
Sponsor: Hao Yonggang

 
 
 
 
Intensive blood pressure control after endovascular thrombectomy for 
acute embolic stroke (INTENSE): a multicentre, open-label, blinded-
endpoint, randomized controlled trial 
 
 
Principal Investigator：Yonggang Hao 
Responsible Institution：The Fourth Affiliated Hospital of Soochow 
University 
Sponsor/Project Source ：Department of Neurology, The Fourth 
Affiliated Hospital of Soochow University 
 
 
 
Study Duration：2024.10.1-2026.09.30 
Version Date：2024-08-03                   Version Number：V1.0 
 

 
 
 
Abbreviation： 
AE  
Adverse event  
ALT 
Alanine aminotransferase 
aSICH 
Asymptomatic intracerebral hemorrhage 
ASPECTS  
Alberta Stroke Program Early CT Score  
AST 
Aspartate transaminase 
CRF  
Case record form  
CT  
Computed tomography  
CTA  
Computed tomography angiography  
DSA 
Digital subtraction angiography 
EQ-5D  
EuroQoL Group 5-dimension self-report questionnaire 
mTICI 
Modified thrombolysis in cerebral infarction 
GFR 
Glomerular filtration rate 
ITT  
Intention to treat  
MRA 
Magnetic resonance imaging angiography 
MRI  
Magnetic resonance imaging  
mRS  
Modified Rankin scale  
NIHSS  
National Institute of Health Stroke Scale  
PP 
Per-protocol 
SAE  
Serious adverse event  
SICH 
Symptomatic intracranial hemorrhage 
 
 

 
 
CONTENTS 
1. Background .................................................................................................................. 1 
2. Objectives ..................................................................................................................... 3 
3. Design ............................................................................................................................ 4 
4. Patient selection ........................................................................................................... 4 
4.1 Inclusion criteria .................................................................................................... 4 
4.2 Exclusion criteria ................................................................................................... 4 
4.3 Criteria for withdrawal ......................................................................................... 5 
4.5 Privacy protection .................................................................................................. 6 
5. Sample size calculation ................................................................................................ 6 
6. Randomization ............................................................................................................. 6 
7. Medication protocol ..................................................................................................... 7 
7.1. Intensive blood pressure control group (experimental group) ......................... 7 
7.2. Less intensive blood pressure control group (control group) ........................... 7 
8. Outcomes ...................................................................................................................... 8 
8.1 Primary efficacy outcome ..................................................................................... 8 
8.3 Secondary efficacy outcome .................................................................................. 8 
8.4 Secondary safety outcomes ................................................................................... 8 
9. Statistical analysis ........................................................................................................ 9 
9.1 Statistical analysis populations ............................................................................. 9 
9.2 Statistical analysis methods .................................................................................. 9 
10. Study steps .................................................................................................................. 9 
11. Study schema............................................................................................................ 10 
12. Schedule of evaluations ........................................................................................... 11 
13. Management of adverse events during and after the study ................................. 12 
13.1 Adverse event (AE) ............................................................................................ 12 
13.2 Severity assessment of AEs ............................................................................... 12 
13.3 SAEs .................................................................................................................... 12 
13.4 AEs reporting ..................................................................................................... 12 

 
 
14. Follow-up and medical measures after study completion .................................... 13 
15. Data retention .......................................................................................................... 13 
16. References................................................................................................................. 14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

1 
 
1. Background 
The latest findings from the Global Burden of Disease study indicate that China experiences 3.94 
million new stroke cases annually, with a total of 28.76 million stroke patients, and 2.19 million 
stroke-related deaths each year [1]. Stroke is the third leading cause of death [2] and the primary 
cause of years lived with disability in China [1]. Among different subtypes of stroke, ischemic stroke 
accounts for the highest proportion, constituting 86% of stroke cases in individuals aged 40 and 
above [3], thereby placing a significant burden on both families and society. 
Endovascular thrombectomy is one of the primary treatments for acute ischemic stroke due to 
large artery occlusion [2,3]. For acute anterior circulation large artery occlusion stroke, 
approximately 78%-96% of patients can achieve vessel recanalization through endovascular 
thrombectomy [4-8]. However, vessel recanalization does not equate to a good prognosis. The 
DIRECT-MT study found that the recanalization rates for direct thrombectomy and thrombectomy 
after intravenous thrombolysis within 4.5 hours of onset are 79.4% and 84.5%, respectively, while 
the good functional outcome rates are only 36.4% and 36.8% [5]. This mismatch suggests that solely 
pursuing vessel recanalization is insufficient to significantly improve clinical outcomes for stroke 
patients. Therefore, further researches on strategies to alleviate ischemia-reperfusion injury, based 
on vessel recanalization, holds the potential to overcome challenges in this field and provide new 
perspectives for the treatment of acute anterior circulation large artery occlusion stroke. 
Blood pressure is a critical clinical management parameter that is closely linked to the prognosis 
of stroke patients. Observational studies suggest that elevated blood pressure is associated with 
worse functional outcome at 3 months in acute ischemic stroke patients undergoing thrombectomy 
[9-13]. Recent meta-analyses have demonstrated that high 24-hour mean systolic blood pressure 
following mechanical thrombectomy is correlated with both 3-month functional impairment and 
mortality [14, 15]. Currently, several randomized controlled trials have been conducted to 
investigate the optimal blood pressure management targets following intravascular therapy in 
patients with anterior circulation stroke. The results of the BP TARGET study [16] indicated that a 
greater reduction in systolic blood pressure within 24 hours following endovascular treatment was 
associated with better prognosis. However, no significant difference in 3-month outcomes was 
observed between the intensive SBP target group (systolic blood pressure between 100-129 mmHg 

2 
 
within 24 hours after successful endovascular therapy) and the standard SBP target group (systolic 
blood pressure between 130-185 mmHg within 24 hours after successful endovascular therapy). In 
this study, the difference in blood pressure between the intensified hypotension and standard blood 
pressure groups was relatively modest (average systolic blood pressure within 24 hours was 128 
mmHg and 138 mmHg, respectively), which may have been insufficient to detect the potential 
benefits of a further reduction in systolic blood pressure. On this basis, the ENCHANTED2/MT 
study [17] employed a grouping strategy with more pronounced differences in blood pressure and 
found that, compared to the less intensive treatment group (systolic blood pressure between 140-
180 mmHg within 72 hours), the more intensive treatment group (systolic blood pressure <120 
mmHg within 72 hours) exhibited a higher proportion of poor functional outcome at 3 months. 
However, no significant differences were observed between the two groups in terms of symptomatic 
intracranial hemorrhage or 3-month mortality [17]. The recently published OPTIMAL-BP study [18] 
reached a conclusion consistent with that of the ENCHANTED2/MT study: the three-month poor 
functional outcome rate in the intensive management group (systolic blood pressure <140 mmHg 
within 24 hours) was significantly higher than that in the conventional management group (systolic 
blood pressure between 140-180 mmHg within 24 hours). Additionally, no significant differences 
were observed in the incidence of symptomatic intracranial hemorrhage or in the three-month 
stroke-related mortality between the two groups. The results of the BEST-II study [19], published 
almost simultaneously, demonstrated that lower SBP targets less than either 140mmHg or 
160mmHg after successful endovascular therapy did not meet prespecified criteria for futility 
compared with an SBP target of 180mmHg or less. Therefore, it cannot be concluded that lower 
postoperative blood pressure targets are harmful [19]. In summary, existing studies present 
inconsistent recommendations regarding blood pressure management following successful 
reperfusion with endovascular thrombectomy, likely due to differences in populations, interventions, 
and other factors. Further precise researches are necessary to better define the optimal strategy. 
The aforementioned randomized controlled trials did not fully account for the impact of stroke 
etiology on the results. Atherosclerosis and embolism are the two most common causes of acute 
ischemic stroke [20]. Patients with large large-artery atherosclerotic stroke often have long-term 
atherosclerotic stenosis of vessels, which promotes collateral circulation, resulting in better 

3 
 
collateral circulation compared to embolic stroke patients [21-23]. Studies have indicated that blood 
pressure variability following vascular recanalization is linked to prognosis in patients with poor 
collateral circulation, but not in those with good collateral circulation [24-26]. Thus, patients with 
embolic strokes may be more susceptible to the effects of blood pressure. A recent study confirmed 
this view by analyzing blood pressure data from 147 patients with atherosclerotic stroke and 273 
patients with cardioembolic stroke [27]. The study found that in patients with cardioembolic stroke, 
greater blood pressure variability within 24 hours after endovascular therapy was associated with a 
lower risk of functional independence at 3 months and a higher risk of cerebral hemorrhage. 
However, these correlations were not observed in patients with atherosclerotic stroke [27]. After 
acute ischemic stroke, impaired cerebral autoregulation makes blood flow in penumbra highly 
sensitive to blood pressure [28]. Elevated blood pressure can increase cerebral perfusion pressure 
and induce microvascular dilation, which may trigger microvascular spasm, further damage the 
blood-brain barrier, and convert ischemic vessels into channels for cerebral edema and hemorrhagic 
transformation [15, 29]. Conversely, excessively low blood pressure can result in inadequate 
cerebral blood flow, causing hypoperfusion, enlarging the infarct, and contributing to a poor 
prognosis [30]. After endovascular thrombectomy, patients with large-artery atherosclerotic stroke 
often have residual stenosis. Intensive blood pressure control in these patients may lead to 
hypoperfusion and exacerbate ischemic symptoms, thus blood pressure should be maintained at a 
relatively higher level. In contrast, for patients with embolic stroke, as there is no residual stenosis 
in the vessels, the primary concern after vascular recanalization is preventing hyperperfusion-related 
hemorrhagic transformation, and blood pressure should be kept at a relatively lower level. 
Compared to patients with large artery atherosclerotic stroke, those with embolic stroke may require 
more stringent blood pressure management. Previous studies that directly pooled patients with 
different stroke etiologies may have masked the impact of blood pressure on prognosis. 
Therefore, we proposed a multicenter randomized controlled trial to investigate the impact of 
early intensive blood pressure control on the prognosis of patients with embolic stroke after 
successful reperfusion following endovascular thrombectomy. 
2. Objectives 
To investigate the safety and efficacy of intensive blood pressure control after successful 

4 
 
reperfusion following thrombectomy in patients with acute anterior circulation large artery embolic 
stroke. 
3. Design 
The study employs a multicenter, prospective, randomized, endpoint-blinded, parallel-controlled 
trial design. Patients with acute anterior circulation large artery occlusive stroke, who receive 
successful reperfusion after endovascular thrombectomy within 4.5 or 6.0 hours of onset, without 
significant in-situ or proximal vessel stenosis, and with sustained elevated systolic blood pressure 
(≥140 mmHg for >10 minutes), will be enrolled according to the clinical inclusion and exclusion 
criteria. The enrolled patients will be randomly assigned to the experimental group or control group 
(1:1). The experimental group will undergo intensive blood pressure management (target systolic 
pressure <120 mmHg, achieved and maintained within 1 hour for 48 hours), while the control group 
will have less intensive blood pressure control (target systolic pressure 140-180 mmHg). Patients 
will be followed up for 3 months to assess their prognosis. 
4. Patient selection 
4.1 Inclusion criteria 
Age ≥ 18 years; 
To receive endovascular thrombectomy <24 hours after the onset of symptoms； 
Diagnosed with acute anterior circulation ischemic stroke; 
National Institutes of Health Stroke Scale (NIHSS) score ≤ 30; 
Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6; 
Computed Tomography Angiography (CTA), Magnetic Resonance Angiography (MRA), or 
Digital Subtraction Angiography (DSA) confirming occlusion of the intracranial internal carotid 
artery or M1/M2 segment of the middle cerebral artery; 
Successful recanalization of the occluded vessel without in-situ or proximal stenosis (modified 
Treatment in Cerebral Infarction, mTICI ≥ 2b); 
Sustained elevated systolic blood pressure (≥140 mmHg for at least two consecutive 
measurements, separated by >10 minutes) within 3 hours of reperfusion; 
Written informed consent provided by the patient or their legal representative. 
4.2 Exclusion criteria 

5 
 
Pre-existing stroke disability defined by a modified Rankin score (mRS) >2； 
Unlikely to benefit from or tolerate endovascular thrombectomy, such as severe allergic reaction 
to contrast agents; 
Failure to achieve mTICI ≥ 2b with endovascular intervention, or presence of in situ or proximal 
vascular stenosis; 
Patients with contraindications for the use of antihypertensive medications, such as allergy to 
components; 
Intracranial space-occupying lesions, including brain tumors and vascular malformations; 
Patients with severe liver or renal dysfunction, or those receiving dialysis (severe liver 
dysfunction is defined as alanine aminotransferase [ALT] > 3 times the upper limit of normal or 
aspartate aminotransferase [AST] > 3 times the upper limit of normal; severe renal dysfunction is 
defined as serum creatinine > 3.0 mg/dL [265.2 μmol/L] or glomerular filtration rate [GFR] < 30 
mL/min/1.73 m²)； 
Serious illness with life expectancy of <6 months; 
Lactating women; 
Participation in other interventional clinical trials within the past 3 months; 
Any other conditions that render patients unsuitable for participation in this study or unable to 
complete the study process, such as psychiatric disorders, cognitive or emotional impairments, or 
physical conditions that hinder compliance with study procedures and follow-up. 
4.3 Criteria for withdrawal 
The study should be terminated if any of the following conditions occur: 
Voluntary withdrawal, participants can freely withdraw at any time; 
Deliberate or inadvertent non-compliance with the study procedures; 
Any other circumstances where the investigator deems that continuing the study would harm the 
patient's health; 
Patients can withdraw from the study at any stage for any reason. Similarly, the investigators have 
the right to terminate a patient's participation in case of an emergency medical condition. For 
patients who withdraw, the investigator must inquire about the reason for withdrawal and whether 
any adverse events (AE) occurred. If the withdrawal is due to an AE, follow-up should be conducted 

6 
 
until the AE is resolved, unless the investigators deem that the condition is due to the patient's 
underlying disease and is unlikely to resolve. The reason for withdrawal and the date must be 
recorded in the case report form (CRF). 
4.4 Criteria for dropout 
Patients who are unable to complete the 3-month follow-up due to subjective or objective reasons. 
4.5 Privacy protection 
Patients' medical records (study case records/CRFs, laboratory reports, etc.) will be securely 
stored at the hospital, with clinical test results well documented. Only the researchers involved in 
this study, the ethics committee, and regulatory authorities will be permitted to access the patient's 
medical records. Any public reports on the study findings will not disclose any patient identifying 
information. We will make every effort, within the bounds of the law, to protect the privacy of 
patients' medical data. In accordance with medical research ethics, except for personal privacy 
information, trial data will be accessible for public inquiry and sharing, limited to web-based 
electronic databases. 
5. Sample size calculation 
Based on published literature and clinical experience, the estimated 90-day functional 
independence rate (defined as mRS ≤ 2) in the control group is 35%. Using a two-tailed significance 
level of α = 0.05, with 80% statistical power (1-β = 0.8), and a 1:1 allocation ratio between the 
experimental and control groups, we estimate that 376 participants per group are needed to detect a 
10% improvement in the functional independence rate between groups. Considering a 20% dropout 
rate, a total of 910 subjects are needed to be enrolled, with 455 participants in each group. 
Randomization will be performed using block randomization with block size of 10 (with at least 
10 participants per center). For practical implementation, each center will be allocated a block, for 
example, if Center 1 plans to enroll 20 participants, blocks 1-2 will be allocated. This randomization 
scheme will be followed accordingly. If stratification variables are used, randomization will be 
performed within each stratum. 
6. Randomization 
Patients will be randomly assigned to two groups in a 1:1 ratio. Stratified block randomization 
will be used, with stratification by study center and intravenous thrombolysis. A 1:1 randomization 

7 
 
sequence will be generated. The randomization process will be managed using the "Jinling mouse" 
app. 
7. Medication protocol 
Blood pressure will be continuously monitored using a noninvasive device applied to the 
nonparalyzed arm or the right arm. The measurement intervals are as follows: every 15 minutes 
within the first hour post-randomization, every hour from 2 to 6 hours, every 6 hours from 4 to 24 
hours, and then twice daily until day 7 (if the patient is discharged or dies before day 7, monitoring 
will be discontinued). 
Given the clinical uncertainties regarding the potential benefits and risks, this study encourages 
adherence to the protocol but allows for adjustments to the treatment plan based on clinical needs. 
Nicardipine is recommended for blood pressure management, but other antihypertensive 
medications may be also selected according to the clinician's judgment. 
Nicardipine injection administration protocol: dilute with saline or 5% glucose injection to 
prepare a solution containing 0.01–0.02% nicardipine hydrochloride (0.1–0.2 mg per 1 mL). 
Administer by intravenous infusion, starting at a rate of 2–10 μg/kg body weight per minute. Once 
the target blood pressure is achieved, adjust the infusion rate while continuously monitoring blood 
pressure. If necessary, intravenous administration can be increased to a dose of 10–30 μg/kg body 
weight per minute. 
7.1. Intensive blood pressure control group (experimental group) 
The target blood pressure is <120 mmHg within 1 hour after randomization, and this level should 
be maintained for at least 48 hours. Intravenous antihypertensive treatment should begin 
immediately after randomization. A systolic pressure of 100 mmHg is the threshold for 
discontinuing both antihypertensive and vasopressor therapy. Oral antihypertensive agents may be 
used once blood pressure stabilizes. Care should be taken to avoid the occurrence of hypotension. 
7.2. Less intensive blood pressure control group (control group) 
The target blood pressure is 140-180 mmHg within 1 hour after randomization, and this level 
should be maintained for at least 48 hours. Intravenous antihypertensive therapy is preferred. 
Antihypertensive agents should be used intravenously when systolic pressure exceeds 180 mmHg, 
and discontinued when systolic pressure is ≤150 mmHg. Oral antihypertensive agents may be used 

8 
 
once blood pressure stabilizes. Even if systolic pressure drops below 140 mmHg, vasopressors 
should not be used unless hypotension occurs. 
8. Outcomes 
8.1 Primary efficacy outcome  
Functional independence (90-day mRS score ≤ 2). 
8.2 Primary safety outcomes 
Rate of symptomatic intracranial hemorrhage (sICH), defined by the Heidelberg Bleeding 
Classification criteria [31]; 
All-cause mortality at 3 months. 
8.3 Secondary efficacy outcome 
mRS score 0–1 at 90 days; 
mRS score 5–6 at 90 days; 
Functional recovery, defined by 90-day mRS score improvement (shift analysis); 
Infarct volume at 24 hours; 
Change in infarct volume at 24 hours (compared to baseline); 
NIHSS score at 24 hours; 
Change in NIHSS score at 24 hours (compared to baseline); 
24-hour NIHSS score 0–1 or improvement >8 points (%); 
Change in NIHSS score at 7 days; 
Brain edema volume at 7 days; 
Health-related quality of life at 90 days (assessed by EQ-5D score). 
8.4 Secondary safety outcomes 
Asymptomatic intracerebral hemorrhage (aSICH); 
Large cerebral infarction or surgical intervention for intracerebral hemorrhage; 
Complications excluding intracerebral hemorrhage (including gastrointestinal bleeding, urethral 
bleeding, oral or nasal mucosal bleeding, and subcutaneous hematomas);  
Non-hemorrhagic severe adverse events (including brain herniation, pneumonia, respiratory failure, 
circulatory failure, stress ulcers, secondary epilepsy, urinary tract infections, sepsis, renal failure, acute 
coronary syndrome, venous thromboembolism, and psychiatric symptoms); 

9 
 
Procedure- or device-related complications (including arterial rupture, arterial dissection, 
complications at the vascular puncture site, and vasospasm). 
9. Statistical analysis 
9.1 Statistical analysis populations 
Intention-to-Treat (ITT) Population: This population will include all randomized patients, 
regardless of whether they receive the intended intervention. A modified ITT analysis will be 
conducted based on the principle of the closest approach to the ITT population. Patients who 
withdraw consent before the blood pressure intervention, do not undergo the assigned procedure 
after randomization, lack endpoint data, refuse follow-up, or are lost to follow-up will be excluded 
from the statistical analysis. The modified ITT analysis will be used to evaluate the effectiveness 
and safety of the treatment regimen. 
Per-Protocol (PP) Population: This population will exclude all patients with significant protocol 
violations, such as those who are under 18 years of age, have a final diagnosis other than acute 
ischemic stroke, have sustained systolic blood pressure <140 mmHg post-surgery, do not achieve 
reperfusion (mTICI <2b), have a pre-stroke mRS score of 3-5, lack 3-month follow-up data, or do 
not achieve the expected blood pressure control. The PP analysis will serve as a supplement to the 
modified ITT analysis. 
9.2 Statistical analysis methods 
For continuous variables that follow a normal distribution, data will be presented as mean ± 
standard deviation. For continuous variables that do not follow a normal distribution, data will be 
presented as median and interquartile range. Between-group comparisons will be performed using 
the independent t-test or Mann-Whitney U test. Categorical or ordinal data will be summarized 
using frequencies and percentages. For comparisons of categorical data between two groups, the χ² 
test or Fisher's exact test will be used; for ordinal data, the Mann-Whitney U test will be applied. 
All statistical analyses will be performed using SPSS software. A p-value < 0.05 will be 
considered statistically significant. 
10. Study steps 

10 
 
After preliminary screening, patients who meet the criteria for endovascular intervention will 
undergo the procedure. Endovascular treatment methods include mechanical thrombectomy and 
aspiration. 
At the end of the endovascular procedure, angiography will be used to assess successful 
reperfusion of the occluded vessel without in-situ or proximal arterial stenosis, with mTICI ≥ 2b. 
Additionally, the patient’s systolic blood pressure will be continuously elevated (≥140 mmHg, 
maintained for >10 minutes). 
Randomization. 
The intensive blood pressure control group will receive more intensive blood pressure 
management (target systolic blood pressure of 120 mmHg, achieved within 1 hour and maintained 
for 48 hours). The less intensive blood pressure control group will not have strict blood pressure 
control (target systolic blood pressure of 140-180 mmHg). 
Follow-up and data collection. 
11. Study schema 
 
 
 
 
 
 
 
 
 
 
 
Acute anterior circulation ischemic stroke (within 24 hours) 
Successful reperfusion of the occluded vessel without in-situ 
or proximal arterial stenosis after endovascular intervention, 
with mTICI ≥ 2b and sustained systolic blood pressure 
elevation (≥140 mmHg, maintained for >10 minutes). 
Randomization 
Intensive blood pressure control  
Less intensive blood pressure control 
Baseline, Day 1, Day 7 clinical and imaging data collection 

11 
 
 
 
Figure 1. Study schema 
 
12. Schedule of evaluations 
Evaluation 
Baseline (Prior 
randomisation) 
Treatment phase 
Follow-up phase 
1 day 
7 daysa 
90 days 
Consent 
X 
 
 
 
Eligibility 
X 
 
 
 
Basic information 
X 
 
 
 
Medical history 
X 
 
 
 
Blood pressure 
X 
X 
X 
 
mRS 
X 
 
X 
X 
NIHSS 
X 
X 
X 
 
ASPECTS 
X 
 
 
 
EQ-5D 
 
 
 
X 
Blood tests 
X 
 
 
 
Menstrual 
history/urine 
pregnancy test (female) 
X 
 
 
 
Electrocardiogram 
X 
 
 
 
Details 
of 
rt-PA 
(if 
performed) and endovascular 
thrombectomy 
X 
 
 
 
Brain 
imaging 
(CT
±
CTA/MRI±MRA/DSA) 
X 
X 
X 
 
BP lowering treatment 
 
X 
X 
 
Standard stroke care 
 
X 
X 
X 
90-day mRS 

12 
 
SAEs 
X 
X 
X 
X 
Complications 
 
X 
X 
X 
Completion 
status 
of 
research 
 
 
 
X 
Table 1. Experimental procedures and items to be assessed at each time point 
a：Or the day of discharge (if the patient is discharged before day 7). 
13. Management of adverse events during and after the study 
13.1 Adverse event (AE) 
An AE refers to any unfavorable medical event that occurs in a participant after receiving a 
drug or medical device, but it is not necessarily causally related to the treatment. 
13.2 Severity assessment of AEs 
The intensity or severity of AEs is categorized into four levels: 
• 
Mild: Does not affect daily activities. 
• 
Moderate: Affects daily activities. 
• 
Severe: Results in the loss of ability to perform daily activities. 
• 
Serious: As defined by the serious adverse event (SAE) criteria. 
13.3 SAEs 
An SAE refers to any event occurring during the clinical trial that results in: 
• 
Death; 
• 
Severe deterioration in the health of the patients, users, or others; 
• 
Life-threatening illness or injury; 
• 
Permanent impairment of bodily structure or function; 
• 
Requirement for hospitalization or prolongation of hospitalization; 
• 
Need for medical or surgical intervention to prevent permanent impairment of body 
structure or function, fetal distress, fetal death, or congenital abnormalities/defects. 
Note: Hospitalization planned due to pre-existing conditions or as required by the clinical trial 
protocol, without significant deterioration in health, is not considered an SAE. 
13.4 AEs reporting 

13 
 
Any AE occurring during the trial will be reported by the investigators and clinical sites to the 
relevant national and local regulatory authorities within the specified timeframes, in accordance 
with national regulations. The investigators will assist the regulatory authorities in investigating 
the AE and implementing appropriate corrective and preventive measures. 
Any SAE occurring during the clinical study must be reported by the investigator to the study's 
ethics committee and the clinical research sponsor within 24 hours of becoming aware of the 
event. Additionally, the investigator must complete a serious adverse event form, documenting the 
time of occurrence, severity, duration, measures taken, and outcome. 
The investigators should follow up and record the outcomes of all AEs, tracking patients who 
withdraw from the study due to an AE until the AE is fully resolved. The investigator must assess 
whether the AE is related to the study intervention and provide supporting evidence for this 
assessment. Any clinically significant abnormal findings in clinical or laboratory tests should be 
recorded on the adverse event form, with follow-up observations at least once a week until the 
condition normalizes or returns to baseline levels. 
Researchers should follow up on all adverse events (AEs) to observe and record their outcomes, 
and track patients who withdraw from the study due to an AE until it is fully resolved. Researchers 
must assess whether the AE is related to the research intervention and provide supporting evidence 
for this assessment. All clinically significant abnormalities in clinical or laboratory tests should be 
documented in an AE form and monitored during follow-up, with observations conducted at least 
weekly until normal or baseline levels are restored. 
14. Follow-up and medical measures after study completion 
The patients will be followed up within 3 months after discharge and continue long-term 
secondary prevention treatment for cerebral infarction. 
15. Data retention 
The CRF is prepared in triplicate: one copy is retained by the sponsor, one by the participating 
institution, and one by the statistical unit. Demographic data, relevant medical history, physical 
examinations, laboratory test results, concomitant medications, and adverse events are recorded in 
the CRF as raw data, with any information related to the subject's privacy documented only in the 
original medical records. 

14 
 
Researchers must store research documents securely according to relevant guidelines. Key 
documents should be retained for 5 years after the completion of the clinical study. After this 
period, the investigator should promptly contact the sponsor to discuss the handling of the study 
materials. 
16. References 
1. 
Ma Q, Li R, Wang L, Yin P, Wang Y, Yan C, et al. Temporal trend and attributable risk 
factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease 
Study 2019. Lancet Public Health. 2021;6(12):e897-e906. 
2. 
Wu. J, Zhou. M, Su. X. China Mortality Cause Monitoring Dataset（2021）: China Science 
and Technology Press; 2023. 
3. 
Tu WJ, Zhao Z, Yin P, Cao L, Zeng J, Chen H, et al. Estimated Burden of Stroke in China in 
2020. JAMA Netw Open. 2023;6(3):e231455. 
4. 
Suzuki K, Matsumaru Y, Takeuchi M, Morimoto M, Kanazawa R, Takayama Y, et al. Effect 
of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional 
Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial. 
Jama. 2021;325(3):244-53. 
5. 
Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, et al. Endovascular 
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7. 
Zi W, Qiu Z, Li F, Sang H, Wu D, Luo W, et al. Effect of Endovascular Treatment Alone vs 
Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients 
With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial. Jama. 2021;325(3):234-
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8. 
Fischer U, Kaesmacher J, Strbian D, Eker O, Cognard C, Plattner PS, et al. Thrombectomy 
alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, 
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9. 
Ding X, Xu C, Zhong W, Gong X, Zhou Y, Chen Z, et al. Association of maximal systolic 
blood pressure with poor outcome in patients with hyperattenuated lesions on immediate 
NCCT after mechanical thrombectomy. J Neurointerv Surg. 2020;12(2):127-31. 
10. 
Maïer B, Gory B, Taylor G, Labreuche J, Blanc R, Obadia M, et al. Mortality and Disability 
According to Baseline Blood Pressure in Acute Ischemic Stroke Patients Treated by 
Thrombectomy: A Collaborative Pooled Analysis. J Am Heart Assoc. 2017;6(10). 
11. 
Goyal N, Tsivgoulis G, Iftikhar S, Khorchid Y, Fawad Ishfaq M, Doss VT, et al. Admission 
systolic blood pressure and outcomes in large vessel occlusion strokes treated with 
endovascular treatment. J Neurointerv Surg. 2017;9(5):451-4. 

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12. 
Goyal N, Tsivgoulis G, Pandhi A, Dillard K, Alsbrook D, Chang JJ, et al. Blood pressure 
levels post mechanical thrombectomy and outcomes in non-recanalized large vessel occlusion 
patients. J Neurointerv Surg. 2018;10(10):925-31. 
13. 
Maïer B, Turc G, Taylor G, Blanc R, Obadia M, Smajda S, et al. Prognostic Significance of 
Pulse Pressure Variability During Mechanical Thrombectomy in Acute Ischemic Stroke 
Patients. J Am Heart Assoc. 2018;7(18):e009378. 
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Malhotra K, Goyal N, Katsanos AH, Filippatou A, Mistry EA, Khatri P, et al. Association of 
Blood Pressure With Outcomes in Acute Stroke Thrombectomy. Hypertension. 
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