Parallel Group, Randomized Clinical Trial of Direct Intra-arterial Thrombectomy Versus Intravenous Thrombolysis With Intra-arterial Thrombectomy for Patients With Large Vessel Occlusion of the Anterior Circulation
Phase: NA
Conditions: Ischemic Stroke, Large Vessel Occlusion, Thrombectomy, Thrombosis, Alteplase
Sponsor: Changhai Hospital

 
1 
 
 
 
 
Direct Intra-arterial thrombectomy in order to Revascularize AIS 
patients with large vessel occlusion Efficiently in Chinese Tertiary 
hospitals: a Multicenter randomized clinical Trial (DIRECT-MT) 
 
 
 
 
Project leaders:  
Liu Jianmin,Deng Benqiang 
Charles Majoie, Yvo Roos 
Sponsor: Changhai Hospital Affiliated to the Second Military 
Medical University 
CRO: Cardiovascular Chinese Research Center 
Protocol No.: CH01 
Version No.: V3.0 
Date: August 20, 2019 
 
 
 
 
Statement of Confidentiality 
The information contained in this document involves trade secrets and business information, which is confidential or 
proprietary and shall not be disclosed by any person unless required by regulations. Any individual who has access to the 
document shall be aware that the document is proprietary or confidential and shall not disclose the document without 
authorization. The above restrictions on the confidentiality of the document will apply to any proprietary or confidential data 
provided to you in the future. 

 
2 
 
 
 
Protocol title: 
Direct Intra-arterial thrombectomy in order to Revascularize AIS patients with large vessel occlusion 
Efficiently in Chinese Tertiary hospitals: a Multicenter randomized clinical Trial (DIRECT-MT) 
 
 
Protocol ID 
CH01 
Version 
3.0 
Date 
August 20, 2019 
Project leaders 
Prof dr Liu Jianmin, Changhai Hospital Affiliated to the Second Military Medical 
University 
 
Prof dr Deng Benqiang, Changhai Hospital Affiliated to the Second Military 
Medical University 
 
Prof dr Charles Majoie, Academisch Medisch Centrum bij de Universitieit van 
Amsterdam (AMC)  
 
Prof dr Yvo Roos, Academisch Medisch Centrum bij de Universitieit van 
Amsterdam (AMC) 
Coordinating 
investigators 
Prof dr Yang Pengfei, Changhai Hospital Affiliated to the Second Military 
Medical University 
 
Prof dr Zhang Yongwei, Changhai Hospital Affiliated to the Second Military 
Medical University 
Sponsor 
Changhai Hospital Affiliated to the Second Military Medical University 
Subsidizing parties 
Stroke Prevention and Control Engineering Commission of National Health and 
Family Planning Commission of the People's Republic of China, Wu Jieping 
Medical Foundation 
CRO 
Cardiovascular Chinese Research Center 
 
 

 
3 
 
 
Protocol Signature Sheet 
 
 
Name 
Signature 
Date 
Sponsor: 
 
Changhai Hospital Affiliated to the 
Second 
Military 
Medical 
University 
 
 
 
 
 
 
 
 
 
I have read this trial protocol carefully and recognize that this protocol covers all the necessary 
contents for the implementation of the trial. I will conduct the study according to the protocol and 
complete the study within the specified period of time. 
 
I will provide copies of this study protocol and all relevant information to all staff who assist me in 
conducting this study. I will discuss these materials with them to ensure that they fully understand 
the test drug and how to conduct the trial. 
 
 
Name 
Signature 
Date 
[Principal investigators]: 
 
 
 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
4/48 
Contents 
List of abbreviations and definitions of terms 
7 
SUMMARY 
9 
1. 
Introduction and rationale 
11 
2. 
Study objectives 
12 
3. 
Study design 
12 
4. 
Study population 
12 
4.1. Population (Base) 
12 
4.2. Participating centers and center eligibility 
12 
4.3. Inclusion criteria 
13 
4.4. Exclusion criteria 
13 
4.5. Sample size calculation 
14 
5. 
Treatment of subjects 
14 
5.1. Investigational treatment 
14 
5.2. Use of co-intervention 
15 
5.3. Escape medication 
15 
6. 
Investigational product 
15 
6.1. Name and description of investigational product 
15 
6.2. Summary of findings from clinical studies 
15 
6.3. Summary of known and potential risks and benefits 
15 
6.4. Description and justification of route of administration and dosage 
16 
7. 
Non-investigational product 
16 
7.1. Name and description of non-investigational products 
16 
7.2. Summary of findings from clinical studies 
16 
7.3. Summary of known and potential risks and benefits 
16 
8. 
Method 
16 
8.1. Study outcomes 
16 
8.1.1. Main study outcome 
16 
8.1.2. Secondary outcomes 
17 
8.1.3. Safety outcomes 
17 
8.1.4. Other study parameters 
17 
8.2. Randomization, blinding and treatment allocation 
18 
8.3. Study procedures 
18 
8.4. Withdrawal of individual subjects 
18 
8.5. Premature termination of the study 
18 
9. 
Safety reporting 
19 
9.1. Temporary halt for reasons of subject safety 
19 

 
 
Version No.: 3.0; Date: August 20, 2019  
5/48 
9.2. AEs, SAEs and SUSARs 
19 
9.2.1. Adverse events (AEs) 
19 
9.2.2. Serious adverse events (SAEs) 
19 
9.3. Follow-up of adverse events 
20 
9.4. Data Safety Monitoring Board (DSMB) 
20 
10. Statistical analysis 
20 
10.1. Statistical analysis 
20 
10.2. Subgroup analysis 
21 
10.3. Interim analysis 
21 
11. Ethical considerations 
21 
11.1. Regulation statement 
21 
11.2. Recruitment and consent 
21 
11.3. Problems of minors or incapacitated subjects 
22 
11.4. Benefits and risks assessment, group relatedness 
22 
11.5. Compensation for injury 
22 
12. Administrative aspects, monitoring and publication 
22 
12.1. Handling and storage of data and documents 
22 
12.2. Monitoring and quality assurance 
22 
12.3. Amendment 
23 
12.4. Annual progress report 
23 
12.5. Temporary halt and (prematurely) end of study report 
23 
12.6. Public disclosure and publication policy 
23 
13. References 
24 
14. Table 
28 
Table 1 Modified Rankin Scale (35) 
28 
Table 2 Extended Treatment In Cerebral Ischemia (Etici) Scale (36) 
29 
Table 3  NIH Stroke Scale 
30 
Table 4  Barthel Index (40) 
34 
Table 5  EUROQOL 5D-5L (39) 
36 
Table 6  Clot Burden Score for CTA and MRA (46) 
38 
Table 7 Collateral Score(43) 
38 
Table 8 Classification pf Infarct in a New Territory (42) 
39 
Table 9 Report of Suspicious Medical Device Adverse Events 
40 
15. Figure 
42 
Figure 1  DIRECT-MT Trial Logo 
42 
Figure 2 Patient Flow in the Trial 
42 
16. Appendix 
43 

 
 
Version No.: 3.0; Date: August 20, 2019  
6/48 
16.1 Study committees 
43 
Steering Committee 
43 
Data Safety Monitoring Board 
43 
Imaging Assessment Committee 
43 
Adverse Event Adjudication Committee 
43 
Outcome Committee 
44 
16.2  DIRECT-MT recommendations of the Steering Committee with regard to type of 
mechanical thrombectomy and use of thrombolytic agents during endovascular 
procedures. 
44 
General 
44 
Neuroimaging 
44 
Additional thrombolytic agents, dose and type 
44 
Type of mechanical thrombectomy device(s) 
44 
16.3  Imaging requirements 
45 
16.3.1  Minimum baseline imaging requirements 
45 
When 45 
How 45 
16.3.2  Intervention-related angiographic imaging 
45 
When 45 
How 46 
16.3.3  Minimum follow-up imaging requirements 
47 
When 47 
How 47 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
7/48 
List of abbreviations and definitions of terms 
AE 
Adverse event 
AIS 
Acute ischemic stroke 
AR 
Adverse Reaction 
ASA 
Acetyl salicylic acid 
CT 
Computed tomography 
CTA 
Computed tomography angiography  
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics committee 
EU 
European Union 
GCP 
Good Clinical Practice 
IAT 
Intra-arterial treatment 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
Intracerebral hemorrhage 
IMP 
Investigational Medicinal Product 
IU 
International standard unit 
IV 
Intravenous 
MRI 
Magnetic resonance imaging 
NIHSS 
NIH Stroke Scale test 
(S) AE 
(Serious) adverse event 
sICH 
Symptomatic intracerebral hemorrhage 
Sponsor 
The sponsor is the party that commissions the organization or performance of 
the research, for example a pharmaceutical company, academic hospital, 
scientific organization or investigator. A party that provides funding for a study 
but does not commission is not regarded as the sponsor, but referred to as a 
subsidizing party. 

 
 
Version No.: 3.0; Date: August 20, 2019  
8/48 
SUSAR 
Suspected unexpected serious adverse reaction 
tPA 
Tissue plasminogen activator 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
9/48 
SUMMARY 
Protocol title: Direct Intra-arterial thrombectomy in order to Revascularize AIS patients with large 
vessel occlusion Efficiently in Chinese Tertiary hospitals: a Multicenter randomized clinical Trial 
(DIRECT-MT) 
Rationale: Intra-arterial treatment (IAT) by means of retrievable stents has been proven safe and 
effective in patients with acute ischemic stroke with confirmed large vessel occlusion of the anterior 
circulation and in whom the procedure can be started within 6 hours from onset. Despite 
recanalization, a considerable proportion of patients do not recover. This can be attributed to 
potential adverse effects of the intravenous treatment (IVT) prior to IAT. These effects could include 
neurotoxicity, blood brain barrier leakage and thrombus fragmentation through softening of the 
thrombus. 
Another reason for non-recovery in MRCLEAN was the occurrence of symptomatic intracranial 
hemorrhage (sICH) in 7% of patients, which was fatal in 65%. sICH occurred as often in the 
intervention as in the control group, suggesting that this complication could not be attributed to the 
IAT, but rather to pre-treatment with IVT. The HERMES study showed that the incidence of 
symptomatic intracranial hemorrhage was about 4.4% in the western population. Considering the 
high rate of intracranial atherosclerosis in Chinese population, the clinical prognosis after 
thrombectomy may be slightly better. Therefore, we hypothesize that direct IAT may lead to a 4% 
absolute increase in good outcome compared to IAT preceded by IVT. 
Objective: To assess the effect of direct IAT compared to IVT followed by IAT, in patients with acute 
ischemic stroke, caused by a CTA-confirmed occlusion of the anterior circulation (intracranial 
segment of ICA, M1, proximal M2) on functional outcome. 
Study design: This is a parallel group, randomized clinical trial of direct IAT versus IVT with IAT. 
The trial has observer blind assessment of the primary outcome and of neuro-imaging at baseline 
and follow up. 
Study population: Patients with acute ischemic stroke and a confirmed anterior circulation 
occlusion by CTA. Initiation of IVT must be feasible within 4.5 hours from symptom onset. Age must 
be 18 or over and NIHSS 2 or more. 
INCLUSION CRITERIA 
- 
a clinical diagnosis of acute ischemic stroke, 
- 
caused by a large vessel occlusion of the anterior circulation (intracranial segment of ICA 
or middle M1/proximal M2) cerebral artery confirmed by CTA, 
- 
CT or MRI ruling out intracranial hemorrhage, 
- 
eligible for IVT and IAT (within 4.5 hours after symptom onset), 
- 
a score of at least 2 on the NIH Stroke Scale, 
- 
age of 18 years or older, 
- 
written informed consent. 

 
 
Version No.: 3.0; Date: August 20, 2019  
10/48 
EXCLUSION CRITERIA 
- 
Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, 
i.e. mRS >2 
- 
Any contra-indication for IVT, according to guidelines of the American Heart Association, 
i.e.: 
o 
arterial blood pressure exceeding 185/110 mmHg 
o 
blood glucose less than 2.7 or over 22.2 mmol/L 
o 
cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of 
recent infarction on neuro-imaging 
o 
serious head trauma in the previous 3 months 
o 
major surgery or serious trauma in the previous 2 weeks 
o 
gastrointestinal or urinary tract hemorrhage in the previous 3 weeks 
o 
previous intracerebral hemorrhage 
o 
use of anticoagulant with INR exceeding 1.7 
o 
known thrombocyte count less than 100 x 109/L 
o 
treatment with direct thrombin or factor X inhibitors 
o 
treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 
48 hours. 
Intervention: The intervention group will undergo immediate IAT using a stent retriever, as 
recommended by the steering committee. The standard care group will receive IVT 0.9 mg/kg with 
a maximum dose of 90 mg in one hour, followed by IAT using a stent retriever. We strive to reduce 
delays associated with IVT administration to a minimum to adequately assess the effect of IVT itself 
with IAT. 
Main study parameters/outcomes: The primary effect parameter will be the common odds ratio, 
estimated with ordinal logistic regression, which represents the shift on the full distribution of the 
modified Rankin Scale at 3 months. The estimate will be adjusted for the known prognostic variables 
age, pre-stroke mRS, time from onset to randomization, stroke severity (NIHSS) and collaterals and 
adjusted and unadjusted estimates with corresponding 95% confidence intervals will be reported. 
Secondary outcomes include mortality at 90 days, stroke severity at 24±6 hours and 5-7 days, 
recanalization on CTA at 24-72 hours, dichotomous clinical outcome on the mRS and infarct size at 
5-7 days. Safety outcomes include rate of sICH. 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
11/48 
1. 
 Introduction and rationale 
Stroke is a major cause of death and disability. The latest National Epidemiological Survey of Stroke 
in China (1) (Ness-China) showed that: the standardized prevalence, incidence and mortality of stroke 
in China in 2013 were 1114.8/100 thousand person/year, 246.8/100 thousand person/year and 
114.8/100 thousand person/year respectively. In 1985, the prevalence of stroke in China was only 
365/100 thousand person/year (2). In the case of a gradual decline in the incidence and mortality of 
stroke in European and American countries, the incidence of Chinese people gradually increased at 
a rate of 8.7% per year, which was significantly higher than the overall annual incidence of stroke in 
the world (3-5). 
Early 2015, the outlook of acute stroke changed dramatically over the course of a few months. It was 
shown that patients with acute ischemic stroke (AIS) caused by a large vessel occlusion of the 
anterior circulation benefit from intra-arterial treatment (IAT). IAT using a stent retriever leads to an 
absolute increase in good functional outcome in 15% to 25% of patients treated within 6 hours. This 
was first reported in the MR CLEAN trial and later confirmed in 4 other trials (6-10). 
In randomized trials of acute ischemic stroke, intravenous thrombolysis (IVT) with alteplase strongly 
reduced the risk of a poor outcome (11, 12). However, two thirds of the patients treated with IVT within 
3 hours of stroke onset in these trials were dead or dependent at the end of follow-up. In the MR 
CLEAN trial, 67% of the patients in the endovascular treatment group were dead or dependent at 
three months. The high risk of a poor outcome, even after these acute revascularization strategies, 
may to a large extent be explained by no-reflow. No-reflow has been linked to distal micro vascular 
damage or dysfunction as a result of tissue necrosis and cell death, or the intervention simply being 
late. 
Currently the role of IVT in acute ischemic stroke treatment with IAT is unclear. The incidence of 
bleeding complications was similar in MR CLEAN to the frequency in the NINDS IVT trial and SITS 
MOST registry (13, 14). In MR CLEAN, the occurrence of symptomatic intracranial hemorrhage (sICH) 
(7%, fatal in 65%) was similar between the intervention and the control group, suggesting that this 
complication could not be attributed to the IAT, but rather to pre-treatment with IVT. According to the 
meta-analysis of the five RCT results, the incidence of symptomatic intracranial hemorrhage in 
westerners was 4.4%. However, there are differences in the pathogenesis of stroke between eastern 
and western populations. In 2017, a retrospective ACTUAL study based on Chinese population 
showed that 44.3% acute intracranial artery occlusion is caused by atherosclerosis, which was 
significantly higher than westerners. At the same time, there was no significant difference in the 
incidence of sICH between direct endovascular treatment group and bridging treatment group. This 
may remind us that the increased proportion of acute intracranial atherosclerotic occlusion did not 
significantly influence the incidence of sICH. Whether the increase of the stent implantation 
proportion will affect clinical outcome is unknown. In the ACTUAL study,  the incidence of aICH in 
the intravascular treatment group was significantly lower than that in the bridging treatment group 
(28.3% vs. 44.9%, P=0.01).  whether the increase in the proportion of stent implantation will increase 
the incidence of ICH after IVT, which are currently unknown and need to be studied.  
According to the above comprehensive analysis, we hypothesize that direct IAT, without 
pretreatment with IVT, in selected patients may lead to a 4% absolute increase in good outcome 

 
 
Version No.: 3.0; Date: August 20, 2019  
12/48 
because of a reduction in the occurrence of sICH and an increase in treatment effect of IAT. 
MR CLEAN is the earliest and only completed RCT study on the evaluation of the efficacy of IAT. 
This study intends to conduct in-depth cooperation with MR CLEAN study team in the Netherlands, 
and conducts an international prospective multi-center randomized controlled study in both locations 
to explore the differences in the clinical outcome between the two to answer the concept whether 
the clinical outcome of this direct IAT is better than that of the current treatment by comparing direct 
IAT with IVT and IAT bridging treatments, and the efficacy of stents in different populations (12). 
 
2. 
Study objectives 
The primary objective of this trial is to assess the effect of direct IAT compared with IVT followed by 
IAT, on functional outcome in patients with AIS, caused by an anterior circulation occlusion that is 
confirmed by CTA. 
The secondary objective is to explore for superiority of direct IAT relative to IVT followed by IAT. 
The tertiary objective is to assess the effect of direct IAT compared with IVT with IAT on neurological 
recovery (NIHSS), infarct size and occurrence of sICH. 
The fourth objective is to collect thrombi and to analyze them with respect to their potential for 
treatment effect modification. 
 
3. 
Study design 
This is a multicenter phase IV prospective randomized clinical trial with open-label treatment and 
blinded outcome assessment (PROBE). The study will run for 4 years in intervention centers. 
 
4. 
Study population 
 
4.1. Population (Base) 
The latest National Epidemiological Survey of Stroke in China (1) (Ness-China) showed that: the 
standardized prevalence, incidence and mortality of stroke in China in 2013 were 1114.8/100 
thousand person/year, 246.8/100 thousand person/year and 114.8/100 thousand person/year 
respectively. In 1985, the prevalence of stroke in China was only 365/100 thousand person/year (2). 
In the case of a gradual decline in the incidence and mortality of stroke in European and American 
countries, the incidence of Chinese people gradually increased at a rate of 8.7% per year, which was 
significantly higher than the overall annual incidence of stroke in the world (3-5). 
 
4.2. Participating centers and center eligibility 
To be fully eligible for participation in the trial and to include patients in the trial, centers should meet 
the following minimum criteria: 
○ 
Local tertiary hospitals; 
○ 
Centers with experience in conducting acute stroke trials; 

 
 
Version No.: 3.0; Date: August 20, 2019  
13/48 
○ 
It can simultaneously perform intravenous thrombolysis and endovascular thrombectomy, 
and completes more than 30 endovascular treatment of acute ischemic stroke each year, 
○ 
The intervention team should have experience with endovascular interventions for 
cerebrovascular disease (IAT, carotid stenting or aneurysm coiling), peripheral artery 
disease, or coronary artery disease, and the stroke team (which includes neurologists and 
interventionists) should have previous experience with intra-arterial treatment, 
○ 
The intervention team should make use of one or more of the devices that have been 
approved by CFDA. Use of other devices is not allowed in the trial. 
○ 
At least one member of the intervention team should have previous experience with the 
particular device. 
Note: Patients may only be included in the trial when the intervention team that will actually treat the 
patient includes at least one interventionist with previous experience with IAT. 
 
4.3. Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following criteria: 
‒ 
a clinical diagnosis of acute ischemic stroke; 
‒ 
caused by a large vessel occlusion of the anterior circulation (distal intracranial carotid 
artery or middle M1/proximal M2) cerebral artery confirmed by CTA; 
‒ 
CT or MRI ruling out intracranial hemorrhage; 
‒ 
eligible for IVT and IAT (within 4.5 hours after symptom onset); 
‒ 
NIHSS ≥ 2; 
‒ 
age of 18 years or older; 
‒ 
written informed consent. 
 
4.4. Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from participation in this 
study: 
‒ 
Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, 
i.e. mRS >2; 
‒ 
Any contra-indication for IVT, according to guidelines of the American Heart Association (27), 
i.e.: 
○ 
blood pressure > 185/110 mmHg, 
○ 
blood glucose < 2.7 or > 22.2 mmol/L, 
○ 
cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of 

 
 
Version No.: 3.0; Date: August 20, 2019  
14/48 
recent infarction on neuro-imaging, 
○ 
serious head trauma in the previous 3 months, 
○ 
major surgery or serious trauma in the previous 2 weeks, 
○ 
gastrointestinal or urinary tract hemorrhage in the previous 3 weeks, 
○ 
previous intracerebral hemorrhage, 
○ 
use of anticoagulant with INR exceeding 1.7, 
○ 
known thrombocyte count less than 100 × 109/L 
○ 
treatment with direct thrombin or factor X inhibitors, 
○ 
treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 
48 hours. 
 
4.5. Sample size calculation 
We based our estimations on the distribution of the modified Rankin Scale (mrS) in the control group 
of the trial, which we derived from the intervention group of the MR CLEAN trial (9): mRS 0: 3%; mRS 
1: 9%; mRS 2: 21%; mRS 3: 18%; mRS 4: 22%; mRS 5: 6% and mRS 6: 21%. We assumed a 
favorable treatment effect with a common odds ratio (cOR) of 1.163, corresponding to a 4% absolute 
increase in the rate of mRS scores of 0-2. The main purpose is to demonstrate non-inferiority, that 
is, the lower limit of the 95% confidence interval does not cross the pre-specified cOR non-inferiority 
Cutoff of 0.8. In a simulation with 5000 runs we computed the proportion of positive trials, for a given 
sample size. A sample size of 710 was determined to detect the pre-defined non-inferiority with a 
power of 80% and two-sided alpha of 0.05. Using covariate adjustment with at most 25%, a 
conservative 15% sample size reduction can be achieved, plus 5% dropout rate, leading to a final 
sample size of 636, 318 per arm. 
 
5. 
 Treatment of subjects 
 
5.1. Investigational treatment 
Patients in the control group will receive IVT (alteplase) according to the guidelines of the American 
Heart Association. (27) Patients in the intervention group will not receive this treatment (nor placebo) 
and proceed directly with IAT. Patients in both groups will undergo IAT. Please note that to assess 
the effect of IVT itself and not the applied treatment strategy, we strive to reduce delays in the control 
group due to IVT administration to an absolute minimum. Remaining differences between treatment 
groups in time from randomization to groin puncture will be recorded. All stent retriever devices for 
IAT, which are approved by CFDA for this purpose, are allowed in the trial as a first line of defense. 
Other mechanical devices (aspiration devices) are allowed as a second option, when the first device 
has failed according to the interventionist, usually after 3 passes. The further choice of the particular 
device for a certain patient is left to the discretion of the interventionist. 

 
 
Version No.: 3.0; Date: August 20, 2019  
15/48 
The target time from study randomization to groin puncture will be as fast as possible. All patients 
must undergo groin puncture within a median of 60 minutes after randomization. 
 
5.2. Use of co-intervention 
No standard co-medication is advised by the steering committee. Antiplatelet or antithrombotic 
treatment will generally be started at 24 hours after the intervention, according to national protocols. 
 
5.3. Escape medication 
If deemed by the interventionist, local application (intra-arterial) of alteplase is allowed in any of the 
patients included in the DIRECT-MT. Patients in the direct IAT group in whom good recanalization 
(eTICI 2b-3) was not reached, may be treated afterwards with 0.9 mg/kg IVT if the 4.5 hour window 
or maximum dose is not exceeded. Patients who have been pre-treated with i.v. alteplase should 
not receive more than 30mg alteplase during intra-arterial treatment. The steering committee 
recommends that the alteplase is delivered in shots of 5 mg in 5-10 minute intervals. 
In individual cases, an equivalent dose of 400,000 U urokinase, delivered in shots of 50.000 - 
100.000 U, in 5-10 minutes time intervals, is also accepted as escape medication. 
Vessel patency should be checked after each shot. 
 
6. 
Investigational product 
 
6.1. Name and description of investigational product 
The comparator in this trial is IVT with alteplase (actilyse). The intervention is omitting IVT before 
IAT. 
 
6.2. Summary of findings from clinical studies 
The value of IVT in patients with AIS has been determined in multiple RCTs with a potential treatment 
window up to 4.5 hours after symptom onset (30, 31). It has been a standard care for several years. All 
trials investigating the benefit of IAT in AIS had a control group consisting of patients receiving usual 
care (6-9, 32). This meant that few patients were treated directly, without prior IVT. In MR CLEAN, this 
concerned only 55 patients (11%). Subgroup analysis showed a similar effect size in patients not 
treated with IVT (OR = 2.06 [95% Confidence Interval (CI): 0.69-6.13]) as in patients pretreated with 
IVT (OR =1.71 [95% CI: 1.22-2.40]). (9) REVASCAT showed comparable results: 56 patients not 
treated with IVT (OR = 2.6 [95% CI: 1.0-7.1]) as to 76 patients who were pretreated (OR = 1.4 [95% 
CI: 0.8-2.6]). (7) Moreover, in ESCAPE, patients without IV pretreatment seemed to benefit (OR = 2.6 
[95% CI: 1.1-5.9]) from endovascular treatment. (6) When we combined the published data there is 
no heterogeneity (p= 0.78). In a fixed effect model, the effect estimate is quite precise and statistically 
significant (OR = 2.3 [95% CI: 1.5-3.7]). We believe that the data from these three randomized 
controlled trials show that patients not pretreated with IVT may benefit from intervention. 
 
6.3. Summary of known and potential risks and benefits 

 
 
Version No.: 3.0; Date: August 20, 2019  
16/48 
For known possible undesirable effects of actilyse, see the summary of product characteristics 
supplied. 
 
6.4. Description and justification of route of administration and dosage 
The route and dosage of administration are based on the American Heart Association guidelines. 
 
7. 
Non-investigational product 
 
7.1. Name and description of non-investigational products 
Stent-retrievers for IAT are the background treatment in this trial. The devices approved by CFDA 
during the research may be used as primary device for IAT (not limited to the table listed below) 
Device name 
Manufacturer 
Description 
Solitaire 
Medtronic / Covidien 
Retrievable stent 
Trevo 
Stryker 
Retrievable stent 
Revive 
Johnson & Johnson/ Cerenovus 
Retrievable stent 
 
7.2. Summary of findings from clinical studies 
Seven randomized clinical trials that predominantly used stent thrombectomy have been carried out. 
(6-10, 33, 34) All trials showed a beneficial effect of intervention compared to usual care, which most often 
included treatment with iv-alteplase. The effect size ranged from 11 to approximately 25% increase 
in proportion of non-disabled patients at 3 months after randomization. (6-10, 33, 34)The treatment is 
already established as standard of care. (32) As stated in paragraph 7.3, the subgroup analyses of 
recent trials suggest that patients not pretreated with IVT may benefit from intervention. 
 
7.3. Summary of known and potential risks and benefits 
The potential benefits of the intervention have been described in 3.3. The potential risks consist of 
intracranial and extracranial hemorrhage and hemorrhagic infarction, procedure related risks such 
as dissection, perforation and infarctions in other vascular territories, and postprocedural events 
such as infections. In the 5 trials, the risks of hemorrhage and hemorrhagic infarction were equal for 
both the intervention group as the control group. Postprocedural events such as pneumonia and 
other infections occurred in similar frequencies in both groups, and procedure-related events were 
infrequent. 
 
8. 
Method 
 
8.1. Study outcomes 
 
8.1.1. Main study outcome 
The primary outcome is the score on the modified Rankin Scale (Table 1 in Appendix) at 90 days (± 
14 days). (35) The mRS is the preferred disability parameter for clinical trials in stroke. The mRS is an 

 
 
Version No.: 3.0; Date: August 20, 2019  
17/48 
ordinal hierarchical scale incorporating six categories from 0 up to and including 5, and describes 
the range of disability encountered post stroke. ‘Death’ is assigned a score of 6. Assessment of 
outcome on the mRS will be performed by independent assessors, blinded to the allocated and 
actually received treatment. Their assessment will be based on standardized reports of a telephone 
interview by trained research personnel who are not aware of treatment allocation. 
 
8.1.2. Secondary outcomes 
Secondary outcomes are the following: 
‒ 
Death within 90 days (± 14 days) 
‒ 
Pre-interventional recanalization 
‒ 
eTICI score on final angiography of IAT. (36) (Table 2 in Appendix) 
‒ 
Recanalization rate at 24-72 hours, assessed with CTA 
‒ 
Score on the NIHSS at 24±6 hours and 5-7 days. (37) (Table 3 in Appendix) 
‒ 
Final infarct volume at 5-7 days. Final infarct volume will be assessed with the use of an 
automated, validated algorithm. (38) Infarct size at day 5-7 will be compared with plain CT 
and perfusion CT results (if available) at baseline. 
‒ 
Dichotomized mRS of 0-1 vs. 2-6 at 90 days (± 14 days) 
‒ 
Dichotomized mRS of 0-2 vs. 3-6 at 90 days (± 14 days) 
‒ 
Dichotomized mRS of 0-3 vs. 4-6 at 90 days (± 14 days) 
‒ 
Score on the EQ5D-5L and Barthel index at 90 days (± 14 days) (39) (40) 
8.1.3. Safety outcomes 
‒ 
Hemorrhages according to the Heidelberg criteria (40) 
‒ 
sICH scored according to the Heidelberg criteria (41) 
‒ 
Embolization in new territory on angiography during IAT 
‒ 
Occurrence of aneurysma spurium 
‒ 
Occurrence of groin hematoma 
‒ 
Infarction in new territory at 5-7 days (42) (Table 8 in Appendix) 
‒ 
Death from all causes within 90 days (± 14 days) 
8.1.4. Other study parameters 
Baseline parameters that will be recorded include age; sex; previous stroke; conditions such as 
hypertension, diabetes mellitus, atrial fibrillation, myocardial infarction; smoking status; medication 
including antiplatelet agents and anticoagulants; vital parameters such as blood pressure, body 
temperature; weight and height; neurological examinations including NIHSS; laboratory examination 

 
 
Version No.: 3.0; Date: August 20, 2019  
18/48 
including INR, APTT, PLT, glucose, creatinine; and imaging results on admission (e.g. clot burden 
score, table 6 in Appendix). 
We will record the actually received dose, type and timing of iv thrombolytic medication. 
Additionally, we will record time from onset to ER, CT, randomization, start of IAT, first reperfusion 
and end of procedure. The devices and the order in which they are used will be recorded, and the 
type of anesthesia (if any) and sedation will be noted. 
 
8.2. Randomization, blinding and treatment allocation 
The randomization procedure will be computer and web-based. Randomization is allowed when the 
occlusion has been established by CTA. Randomization will be stratified by center. 
It will not be possible to view the treatment allocation before the patient is registered in the study 
database, nor will it be possible to remove the patient from the study after treatment assignment has 
become known. Both patient and treating physician will be aware of the treatment assignment. 
Information on outcome at three months will be assessed through standardized forms and 
procedures, by a trained investigator blinded for treatment allocation. Interviews will be recorded. 
Assessors who are blinded to the treatment allocation will perform assessment of outcome on the 
modified Rankin scale on this information. Results of neuro-imaging will be also assessed in a 
blinded manner. Information on treatment allocation will be kept separate from the main study 
database. The steering committee will be kept unaware of the results of interim analyses of efficacy 
and safety. An independent trial statistician will combine data on treatment allocation with the clinical 
data in order to report to the data monitoring committee (DSMB). 
 
8.3. Study procedures 
All patients will undergo assessment of the NIHSS at baseline, 24±6 hours and 5-7 days, which is 
routine in clinical procedure. It will be carried out by certified assessors. Patients will undergo NCCT 
and CTA at baseline. After 24-72 hours CTA is repeated to determine recanalization. At 5-7 days, 
patients will undergo NCCT to assess infarct size. 
In addition, this trial also makes use of “waste material”: retrieved thrombi during intervention. These 
thromboses will be stored in the participating study centers for follow-up analysis. 
 
8.4. Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without any 
consequences. The investigator can decide to withdraw a subject from the study for urgent medical 
reasons. The data from subjects who do not provide consent will be treated anonymously, and used 
for baseline analysis to further describe this population. At the time of analysis, missing data are 
interpolated, including the final mRS score. The key part of personal data will be cleared. 
 
8.5. Premature termination of the study 
The study will only be terminated prematurely if the Data Safety Monitoring Board recommends 

 
 
Version No.: 3.0; Date: August 20, 2019  
19/48 
stopping. In case of premature termination of the study, the database will be closed after 90 days 
assessment of the last enrolled patient and results will be reported. 
 
9. 
Safety reporting 
 
9.1. Temporary halt for reasons of subject safety 
The sponsor will suspend the study if there is sufficient ground that continuation of the study will 
jeopardize subject health or safety. The sponsor will notify the undue delay caused by temporary 
halt as well as the reason for such an action. The study will be suspended pending further review by 
the EC. The investigator should ensure that all subjects are kept informed. 
 
9.2. AEs, SAEs and SUSARs 
 
9.2.1. Adverse events (AEs) 
Adverse events are defined as any undesirable experience occurring to a subject during the study, 
whether or not considered related to trial procedure. All adverse events reported spontaneously by 
the subject or observed by the investigator or his staff will be recorded. 
 
9.2.2. Serious adverse events (SAEs) 
A serious adverse event is any unfavourable medical occurrence or effect as follows 
‒ 
Results in death; 
‒ 
Life threatening (at the time of the event); 
‒ 
Require inpatient hospitalization or prolongation of existing inpatients’ hospitalization. 
‒ 
congenital anomaly or birth defect; 
‒ 
results in persistent or significant disability or incapacity; 
‒ 
that required medical or surgical intervention to preclude of; 
Any other important medical event that did not result in any of the outcomes listed above due to 
medical or surgical intervention but could have been based upon appropriate medical judgment.  
An elective hospital admission will not be considered as a serious adverse event. Technical 
complications or vascular damage at the target lesion such as perforation or dissection that do not 
lead to clinically detectable SAE and neurological deterioration not caused by intracranial 
hemorrhage, new ischemic stroke, but are considered as consistent with the natural course of the 
ischemic stroke and its treatment, will not be reported immediately. 
Serious adverse events will be immediately, after coming to notice of the investigator, reported to 
the site EC and sponsor. 
The investigator will report the following SAEs occurring in the study period to the sponsor without 

 
 
Version No.: 3.0; Date: August 20, 2019  
20/48 
undue delay of obtaining knowledge of the events: Death from any cause; symptomatic intracranial 
hemorrhage scored, extracranial hemorrhage, aspiration pneumonia, allergic contrast reactions, 
new ischemic stroke in different vascular territory. 
SAEs of this study are reported using the "Suspicious Medical Device Adverse Event Report Form" 
(Table 9 in the appendix).  
 
9.3. Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been reached.  
Depending on the event, follow up may require additional tests or medical procedures as indicated, 
and/or referral to the general physician or a medical specialist. 
SAEs need to be reported till the end of the study in China, as defined in the protocol. 
 
9.4. Data Safety Monitoring Board (DSMB) 
In order to increase the safety of the intervention, the trial will be monitored by an independent DSMB. 
The DSMB will be chaired by a neurologist, and include a neuro-interventionist and an independent 
methodologist/statistician. The DSMB plans to conduct two interim analyses to evaluate the 
treatment effect and the incidence of adverse reactions according to the procedure at the end of the 
90-day follow-up of 1/3 and 2/3 subjects, respectively. During the period of patient enrollment into 
the study, interim analyses of mortality and of any other information that is available on major 
outcomes (including serious adverse events believed to be due to treatment) will be supplied, in strict 
confidence, to the chairman of the DSMB, along with any other analyses that the DSMB may request. 
In the light of these analyses, DSMB will advise the chairman of the Steering Committee if, in their 
view, the randomized comparisons in DIRECT-MT have provided both (i) "proof beyond reasonable 
doubt" that for all, or for some specific types of patients, one particular treatment is clearly indicated 
or clearly contraindicated in terms of a net difference in outcome, and (ii) evidence that might 
reasonably be expected to materially influence patient management. Appropriate criteria of proof 
beyond reasonable doubt cannot be specified precisely, but a difference of at least 3 standard 
deviations in an interim analysis of a major outcome may be needed to justify halting, or modifying, 
the study prematurely. This criterion has the practical advantage that the number of interim analyses 
is of little importance. 
The advice(s) of the DSMB will be sent to the sponsor of the study by the chair of the steering 
committee. Should the sponsor decide not to fully implement the advice of the DSMB, the sponsor 
will send the advice to the EC, including a note to substantiate why (part of) the advice of the DSMB 
will not be followed. 
10. Statistical analysis 
 
10.1. Statistical analysis 
The primary effect parameter will be the common odds ratio, estimated with ordinal logistic 
regression, which represents the shift on the 7-category mRS scale measured at 3 months. The 
estimate will be adjusted for the known prognostic variables age, pre-stroke mRS, time from onset 

 
 
Version No.: 3.0; Date: August 20, 2019  
21/48 
to randomization, stroke severity (NIHSS) and collaterals and adjusted and unadjusted estimates 
with corresponding 95% confidence intervals will be reported. To explore for non-inferiority, we will 
analyze whether the lower bound of the 95% CI crossed 0.8, our pre-specified non-inferiority margin. 
If applicable, the secondary outcomes will be analyzed using linear, logistic, or ordered regression 
analysis method, with the same correction method as the primary outcomes. 
All analyses will be performed according to the intention-to-treat principle. Baseline data by treatment 
allocation will be reported with statistical procedures. Missing values for baseline characteristics will 
be reported. Missing baseline characteristics will be imputed using regression imputation. Pre-
defined subgroups will be analyzed by testing for interaction between the specific baseline 
characteristic and treatment. 
 
10.2. Subgroup analysis 
The effect of intervention on the modified Rankin Scale will be analyzed in subgroups determined by 
the following variables: 
‒ 
Tertiles of time from onset of symptoms to randomization, groin puncture and 
revascularization 
‒ 
Ipsilateral extracranial carotid tandem lesion 
‒ 
Occlusion location 
‒ 
Collateral grades 0 to 3 as defined by Tan et al. (43) (Table 7 in Appendix) 
‒ 
Thrombus characteristics (thrombus perviousness (44), clot burden, density) 
‒ 
Large vessel occlusion due to different etiologies 
 
10.3. Interim analysis 
See Paragraph 9.4. 
 
11. Ethical considerations 
 
11.1. Regulation statement 
The study will be conducted according to the principles of the Declaration of Helsinki (October 2013) 
(45) 
 
11.2. Recruitment and consent 
Following Article 21 of "Standard for quality management of medical device clinical trials" (June 1, 
2016)1, the investigators should adequately explain the details of the clinical trial, including known, 
foreseeable risks and possible adverse event, etc., to the subject or to the guardians of subjects 
 
1 http://www.sda.gov.cn/WS01/CL1101/148101.html 

 
 
Version No.: 3.0; Date: August 20, 2019  
22/48 
without capacity for civil conduct or with limited capacity for civil conduct. After full and detailed 
explanation, the subjects or their guardians sign the name and date in the informed consent form, 
and the investigators also need to sign the name and date in the informed consent form. 
 
11.3. Problems of minors or incapacitated subjects 
Minors (under 18 years old) will not be included in this trial. In the trial, about 50% of patients have 
language defects due to stroke, and about a quarter of the patients may suffer from a certain degree 
of lack of sense of disease. In such case, following the first paragraph of Article 23 of "Standard for 
quality management of medical device clinical trials" (June 1, 2016), for incapacitated subjects, if the 
ethics committee agrees in principle, and investigators believe that subjects participating in clinical 
trials are in their own interest, they can also enter the clinical trial, but their guardians should sign 
the name and date before the trial. 
 
11.4. Benefits and risks assessment, group relatedness 
The expected benefit from direct intra-arterial treatment compared to IVT followed by IAT may 
amount to 4% absolute increase in independent living at 3 months. Patients who have been allocated 
to the control group will be given usual treatment according to international, national and local 
guidelines. This includes treatment with IVT, followed by IAT. 
 
11.5. Compensation for injury 
Each participating center has purchased liability insurance. This insurance provides cover for 
damage to research subjects through injury or death caused by the study. 
 
12. Administrative aspects, monitoring and publication 
 
12.1. Handling and storage of data and documents 
All data will be entered into a web-based database (EDC) by local research personnel. Subject 
records are coded by a unique study number. The local investigators will keep a list showing codes 
and names. Unique documents with identifying information will be stored separately from the study 
database in digital files, categorized by study number on a secure drive system, only accessible to 
the study coordinator. 
 
12.2. Monitoring and quality assurance 
The monitors will arrange visits according to the speed of enrollment of each center and the 
deviations found in the past. In principle, the inspection visit will be arranged within 5 working days 
of the center enrollment. The monitor will validate informed consent and source data for all subjects. 
The monitoring data including but not limited to: in-patient medical records, outpatient medical 
records, follow-up medical records, imaging materials and evaluation forms, etc. At the same time, 
the monitor will check the integrity and consistency of EDC data entry. 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
23/48 
12.3. Amendment 
Amendments are changes made to the research protocol after a favorable opinion by EC has been 
given. All amendments will be notified to the EC that gave a favorable opinion. 
 
12.4. Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the EC once a year. 
Information should be provided: the date of inclusion of the first subject, numbers of subjects included 
and numbers of subjects that have completed the trial, serious adverse events/ serious adverse 
reactions, other problems and amendments. 
 
12.5. Temporary halt and (prematurely) end of study report 
The investigator/sponsor will notify the EC of the end of the study within a period of 8 weeks. The 
end of the study is defined as the last patient’s last visit. 
The sponsor will notify the EC immediately of a temporary halt of the study, including the reason of 
such an action. 
In case the study is ended prematurely, the sponsor will notify the EC within 15 days, including the 
reasons for the premature termination. 
Within one year after the end of the study, the investigator/sponsor will submit a final study report 
with the results of the study, including any publications/abstracts of the study, to the EC and the 
Competent Authority. 
The insurance applies to the damage that becomes apparent during the study or within 4 years after 
the end of the study. 
 
12.6. Public disclosure and publication policy 
The trial has been registered in clinicaltrials.gov. Clinicaltrials: NCT03469206 
The study database will be closed within one month after the last scheduled follow-up date of the 
last included patient. A manuscript which at least describes the study and the answer to the primary 
research question will be submitted to a major clinical journal within 3 months from closure of the 
database. The manuscript will be shared with the financial sponsor(s) one month before submission, 
but the financial sponsor(s) will have no influence on its contents. 
Anonymous data can be requested from the PI with a detailed description containing the aims and 
methods of the study for which the data are intended to be used. Data will be made available for this 
purpose at least 18 months after publication of the main report. Data may also be shared with non-
commercial parties for scientific purposes, including individual patient meta-analyses, and with 
commercial parties for regulatory purposes. 
These purposes should be specified in the informed consent form. 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
24/48 
13. References 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
25/48 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
26/48 
 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
27/48 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
28/48 
14. Table 
 
Table 1 Modified Rankin Scale (35) 
The modified Rankin Scale (mRS) is an ordinal hierarchical scale ranging from 0 to 5, with higher 
scores indicating more severe disability. A score of 6 has been added to signify death. 
Catego
ry 
Short description 
Long description 
0 
No symptoms 
No symptoms 
1 
Symptoms, 
no 
disability 
Minor symptoms that do not interfere with lifestyle 
2 
Slight disability 
Slight disability, symptoms that lead to some restriction in lifestyle, but 
do not interfere with the patient's capacity to look after himself. 
3 
Moderate disability 
Moderate disability, symptoms that significantly restrict lifestyle and 
prevent totally independent existence 
4 
Moderately 
severe 
disability 
Moderately severe disability, symptoms that clearly prevent independent 
existence though not needing constant attention 
5 
Severe disability 
Severe disability, totally dependent patient requiring constant attention 
day and night. 
6 
Death 
Death 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
29/48 
Table 2 
Extended Treatment In Cerebral Ischemia (Etici) Scale (36) 
 
eTICI grade Short 
description 
Long description 
0 
No perfusion 
No antegrade flow beyond the point of occlusion 
1 
Limited 
reperfusion 
Antegrade reperfusion past the initial occlusion, but limited distal branch 
filling with little or slow distal reperfusion 
2a 
<50% reperfusion 
Antegrade reperfusion of less than half of the occluded target artery 
previously ischemic territory (eg, in 1 major division of the MCA and its 
territory) 
2b 
≥50% and <90% 
reperfusion 
Antegrade reperfusion of more than half of the previously occluded 
target artery ischemic territory (eg, in 2 major divisions of the MCA and 
its territories) 
2c 
≥90% reperfusion 
Near complete antegrade reperfusion of the previously occluded target 
artery ischemic territory, except for slow flow or distal emboli in a few 
distal cortical vessels 
3 
100% reperfusion 
Complete antegrade reperfusion of the previously occluded target artery 
ischemic territory, with absence of visualized occlusion in all distal 
branches 
MCA: middle cerebral artery; eTICI; extended treatment in cerebral ischemia scale 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
30/48 
Table 3  NIH Stroke Scale 
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient’s 
performance. (23) Scores range from 0 to 42, with higher scores indicating a more severe deficit. 
Administer stroke scale items in the order listed. Record performance in each category after each 
subscale exam. Do not go back and change scores. Follow directions provided for each exam 
technique. Scores should reflect what the patient does, not what the clinician thinks the patient can 
do. The clinician should record answers while administering the exam and work quickly. Except 
where indicated, the patient should not be coached (i.e. repeated requests to patient to make a 
special effort). 
Instructions 
Scale definition 
1a. Level of consciousness. The investigator 
must choose a response if a full evaluation is 
prevented by such obstacles as an endotracheal 
tube, 
language 
barrier, 
orotracheal 
trauma/bandages. A 3 is scored only if the 
patient makes no movement (other than reflexive 
posturing) in response to noxious stimulation. 
0 = Alert; keenly responsive. 
1 = Not alert; but arousable by minor stimulation to 
obey, answer, or respond. 
2 = Not alert; required repeated stimulation to attend, or 
is obtunded and requires strong or painful stimulation to 
make movements (not stereotyped). 
3 = Responds only with reflex motor or autonomic effects 
or totally unresponsive, flaccid and areflexic. 
1b. LOC Questions: The patient is asked the 
month and his/her age. The answer must be 
correct – there is not partial credit for being close. 
Phasic and stuporous patients who do not 
comprehend the questions will score 2. Patients 
unable to speak because of endotracheal 
intubation, orotracheal trauma, severe dysarthria 
from any cause, language barrier, or any other 
problem not secondary to aphasia are given a 1. 
It is important that only the initial answer be 
graded and that the examiners not “help” the 
patient with verbal or non-verbal clues. 
0 =  Answers both questions correctly. 
1 =  Answers one question correctly. 
2 =  Answers neither question correctly. 
1c. LOC Commands: The patient is asked to 
open and close the eyes and then to grip and 
release the non-paretic hand. Substitute another 
one step command if the hand cannot be used. 
Credit is given if an unequivocal attempt is made 
but not completed due to weakness. If the patient 
does not respond to command, the task should 
be demonstrated to him or her (pantomime), and 
the result scored  
(i.e. follows none, one or two commands). 
Patients with trauma, amputation, or other 
physical impediments should be given suitable 
one-step commands. Only the first attempt is 
scored. 
0 =  Performs both tasks correctly. 
1 =  Performs one task correctly. 
2 =  Performs neither task correctly. 
2. Best Gaze: Only horizontal eye movements 
will 
be 
tested. 
Voluntary 
or 
reflexive 
(oculocephalic) eye movements will be scored, 
but caloric testing is not done. If the patient has 
0= Normal. 
1= Partial gaze palsy; gaze is abnormal in one or both 
eyes, but forced deviation or total gaze paresis is not 
present. 

 
 
Version No.: 3.0; Date: August 20, 2019  
31/48 
a conjugate deviation of the eyes that can be 
overcome by voluntary or reflexive activity, the 
score will be a 1. If a patient has an isolated 
peripheral nerve paresis (CN III, IV or VI), score 
a 1. Gaze is testable in all aphasic patients. 
Patients 
with 
ocular 
trauma, 
bandages, 
preexisting blindness, or other disorder of visual 
acuity or fields should be tested with reflexive 
movements, and a choice made by the 
investigator. Establishing eye contact and then 
moving about the patient from side to side will 
occasionally clarify the presence of a partial gaze 
palsy. 
2= Forced deviation; or total gaze paresis not 
overcome by the oculocephalic maneuver. 
3. Visual: Visual fields (upper and lower 
quadrants) are tested by confrontation, using 
finger counting or visual threat, as appropriate. 
Patients may be encouraged, but if they look at 
the side of the moving finger appropriately, this 
can be scored as normal. If there is unilateral 
blindness or enucleation, visual fields in the 
remaining eye are scored. Score 1 only if a clear-
cut asymmetry, including quadrantanopia, is 
found. If patient is blind from any cause, score 3. 
 Double simultaneous stimulation is performed in 
this case.  
If there is extinction, the patient receives a 1, and 
the results are used to respond to item 11. 
 
0= No visual loss. 
1= Partial hemianopia. 
2= Complete hemianopia. 
3= Bilateral hemianopia  
(blind including cortical blindness) 
4. Facial palsy: Ask or use pantomime to 
encourage the patient to show teeth or raise 
eyebrows and close eyes. Score symmetry of 
grimace in response to noxious stimuli in the 
poorly response or non-comprehending patient. 
If facial trauma/bandages, orotracheal tube, tape 
or other physical barriers obscure the face, these 
should be removed to the extent possible. 
0 = Normal symmetrical movements. 
1= Minor paralysis  
(flattened nasolabial fold, asymmetry on smiling) 
2= Partial paralysis (total or near-total paralysis of 
lower face) 
3= Complete paralysis of one or both sides (absence 
of facial movement in the upper and lower face). 
5. Motor arm: The limb is placed in the 
appropriate position: extend the arms (palms 
down) 90 degrees (if sitting) or 45 degrees (if 
supine). Drift is scored if the arm falls before 10 
seconds. The aphasic patient is encouraged 
using urgency in the voice and pantomime, but 
not noxious stimulation. Each limb is tested in 
turn, beginning with the non-paretic arm. Only in 
the case of amputation or joint fusion at the 
shoulder, the examiner should record the score 
as untestable (UN), and clearly write the 
explanation for this choice. 
0= No drift; limb holds 90 (or 45) degrees for full 10 
seconds. 
1= Drift; limb holds 90 (or 45) degrees, but drifts down 
before full 10 seconds; does not hit bed or other support. 
2= Some effort against gravity; limb cannot get to or 
maintain (if cued) 90 (or 45) degrees, drifts down to bed, 
but has some effort against gravity. 
3= No effort against gravity; limb falls. 
4= No movement. 
UN = Amputation or joint fusion: explain: 
5a = Left Arm. 
5b = Right arm. 
6. Motor leg: The limb is placed in the 
appropriate position: hold the leg at 30 degrees 
0= No drift; leg holds 30-degree position for full 5 
seconds. 

 
 
Version No.: 3.0; Date: August 20, 2019  
32/48 
(always tested supine). Drift is scored if the leg 
falls before 5 seconds. The aphasic patient is 
encouraged using urgency in the voice and 
pantomime, but not noxious stimulation. Each 
limb is tested in turn, beginning with the non-
paretic leg. Only in the case of amputation or 
joint fusion at the hip, the examiner should record 
the score as untestable (UN), and clearly write 
the explanation for this choice. 
1= Drift; leg falls by the end of the 5-second period but 
does not hit bed. 
2= Some effort against gravity; leg falls to bed by 5 
seconds, but has some effort against gravity. 
3= No effort against gravity; leg falls to bed 
immediately. 
4= No movement. 
UN = Amputation or joint fusion: explain: 
6a. Left Leg 
6b. Right Leg. 
7. Limb ataxia: This item is aimed at finding 
evidence of a unilateral cerebellar lesion. Test 
with eyes open. In case of visual defect, ensure 
testing is done in intact visual field. The finger-
nose-finger and heel-shin tests are performed on 
both sides, and ataxia is scored only if present 
out of proportion to weakness. Ataxia is absent 
in the patient who cannot understand or is 
paralyzed. Only in the case of amputation or joint 
fusion, the examiner should record the score as 
untestable 
(UN), 
and 
clearly 
write 
the 
explanation for this choice. In case of blindness, 
test by having the patient touch nose from 
extended arm position. 
0= Absent. 
1= Present in one limb. 
2= Present in two limbs. 
UN = Amputation or joint fusion: explain: 
8. Sensory: Sensation or grimace to pinprick 
when tested, or withdrawal from noxious 
stimulus in the obtunded or aphasic patient. Only 
sensory loss attributed to stroke is scored as 
abnormal and the examiner should test as many 
body areas (arms [not hands], legs, trunk, face) 
as needed to accurately check for hemisensory 
loss. A score of 2, 'severe or total sensory loss', 
should only be given when a severe or total loss 
of sensation can be clearly demonstrated. 
Stuporous and aphasic patients will, therefore, 
probably score 1 or 0. The patient with brainstem 
stroke who has bilateral loss of sensation is 
scored 2. If the patient does not respond and is 
quadriplegic, score 2. Patients in a coma (item 
1a=3) are automatically given a 2 on this item. 
0= Normal; no sensory loss. 
1= Mild-to-moderate sensory loss; patients feels 
pinprick is less sharp or is dull on the affected side; or 
there is a loss of superficial pain with pinprick, but patient 
is aware of being touched.  
2= Severe to total sensory loss; patient is not aware 
of being touched in the face, arm and leg. 
9. Best language: A great deal of information 
about comprehension will be obtained during the 
preceding sections of the examination. For this 
scale item, the patient is asked to describe what 
is happening in the attached picture, to name the 
items on the attached naming sheet and to read 
from 
the 
attached 
list 
of 
sentences. 
Comprehension is judged from responses here, 
as well as to all of the commands in the 
preceding general neurological exam. If visual 
loss interferes with the tests, ask the patient to 
0= No aphasia; normal 
1= Mild-to-moderate aphasia; some obvious loss of 
fluency or facility of comprehension, without significant 
limitation on ideas expressed or form of expression. 
Reduction of speech and/or comprehension, however, 
makes conservation about provided materials difficult or 
impossible. For example, in conversation about provided 
materials, examiner can identify picture or naming card 
content from patient's response.  
2= Severe aphasia; all communication is through 
fragmentary expression; great need for inference, 

 
 
Version No.: 3.0; Date: August 20, 2019  
33/48 
identify objects placed in the hand, repeat, and 
produce speech. The intubated patient should 
be asked to write. The patient in a coma (item 
1a=3) will automatically score 3 on this item. The 
examiner must choose a score for the patient 
with stupor or limited cooperation, but a score of 
3 should be used only if the patient is mute and 
follows no one-step commands. 
questioning, and guessing by the listener. Range of 
information that can be exchanged is limited; listener 
carries burden of communication. Examiner cannot 
identify materials provided from patient response. 
3 = Mute, global aphasia: no usable speech or auditory 
comprehension. 
10. Dysarthria: If patient is thought to be 
normal, an adequate sample of speech must be 
obtained by asking patient to read or repeat 
words from the attached list. If the patient has 
severe aphasia, the clarity of articulation of 
spontaneous speech can be rated. Only if 
patient is intubated or has other physical barriers 
to producing speech, the examiner should 
record the score as untestable (UN), and clearly 
write an explanation for this choice. Do not tell 
the patient why he or she is being tested. 
0= Normal. 
1= Mild-to-moderate dysarthria; patient slurs at least 
some words and, at worst, can be understood by some 
difficulty. 
2= Severe dysarthria: patient's speech is so slurred as 
to be unintelligible in the absence of or out of proportion 
to any dysphasia, or is mute/anarthric. 
UN = Intubated or other physical barrier.  
11. Extinction and Inattention (formerly 
Neglect): Sufficient information to identify 
neglect may be obtained during the prior testing. 
If the patient has a severe visual loss preventing 
visual double simultaneous stimulation, and the 
cutaneous stimuli are normal, the score is 
normal. If the patient has aphasia but does 
appear to attend to both sides, the score is 
normal. The presence of visual spatial neglect or 
anosagnosia may also be taken as evidence of 
abnormality. Since the abnormality is scored 
only if present, the item is never untestable. 
0= No abnormality. 
1= Visual, tactile, auditory, spatial, or personal 
inattention or extinction to bilateral simultaneous 
stimulation in one of the sensory modalities.  
2= Profound hemi-inattention or extinction to more 
than one modality; does not recognize own hand or 
orients to only one side of space. 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
34/48 
Table 4  Barthel Index (40) 
The Barthel index (BI) is an ordinal scale used to measure performance in 10 activities of daily living 
(ADL). Test scores range from 0 to 100, with higher scores indicating better performance in these 
activities. 
Category 
Scale definition 
Feeding 
0 = unable 
5 = needs help cutting, spreading butter, etc., or requires modified diet 
10 = independent 
Bathing 
0 = dependent 
5 = independent (or in shower) 
Grooming 
0 = needs to help with personal care 
5 = independent face/hair/teeth/shaving (implements provided) 
Dressing 
0 = dependent 
5 = needs help but can do about half unaided 
10 = independent (including buttons, zips, laces, etc.) 
Bowels 
0 = incontinent (or needs to be given enemas) 
5 = occasional accident 
10 = continent 
Bladder 
0 = incontinent, or catheterized and unable to manage alone 
5 = occasional accident 
10 = continent 
Toilet use 
0 = dependent 
5 = needs some help, but can do something alone 
10 = independent (on and off, dressing, wiping) 
Transfers (bed to chair 
and back) 
0 = unable, no sitting balance 
5 = major help (one or two people, physical), can sit 
10 = minor help (verbal or physical) 
15 = independent 
Mobility 
(on 
level 
surfaces) 
0 = immobile or < 50 yards 
5 = wheelchair independent, including corners, > 50 yards 
10 = walks with help of one person (verbal or physical) > 50 yards 
15 = independent (but may use any aid; for example, stick) > 50 yards 
Stairs 
0 = unable 
5 = needs help (verbal, physical, carrying aid)  
10 = independent 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
35/48 
Guidelines 
1. The index should be used as a record of what a patient does, not as a record of what a 
patient could do. 
2. The main aim is to establish degree of independence from any help, physical or verbal, 
however minor and for whatever reason. 
3. The need for supervision renders the patient not independent. 
4. A patient's performance should be established using the best available evidence. Asking 
the patient, friends/relatives and nurses are the usual sources, but direct observation and 
common sense are also important. However direct testing is not needed. 
5. Usually the patient's performance over the preceding 24-48 hours is important, but 
occasionally longer periods will be relevant. 
6. Middle categories imply that the patient supplies over 50 per cent of the effort. 
7. Use of aids to be independent is allowed. 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
36/48 
Table 5  EUROQOL 5D-5L (39) 
The EuroQoL 5-dimensions 5-level (EQ-5D-5L) questionnaire is a standardized measure of health 
outcome that has been used extensively in patients with stroke. 
Under each heading, please tick the ONE box that best describes your health TODAY. 
Mobility 
I have no problems in walking about 
 
I have slight problems in walking about 
 
I have moderate problems in walking about 
 
I have severe problems in walking about 
 
I am unable to walk about 
 
Self-care 
 
I have no problems washing or dressing myself 
 
I have slight problems washing or dressing myself 
 
I have moderate problems washing or dressing myself 
 
I have severe problems washing or dressing myself 
 
I am unable to wash or dress myself 
 
Usual activities (e.g. work, study, housework, family or 
leisure activities) 
 
I have no problems doing my usual activities 
 
I have slight problems doing my usual activities 
 
I have moderate problems doing my usual activities 
 
I have severe problems doing my usual activities 
 
I am unable to do my usual activities 
 
 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
37/48 
Pain/discomfort 
 
I have no pain or discomfort 
 
I have slight pain or discomfort 
 
I have moderate pain or discomfort 
 
I have severe pain or discomfort 
 
I have extreme pain or discomfort 
 
Anxiety/depression 
 
I am not anxious or depressed 
 
I am slightly anxious or depressed 
 
I am moderately anxious or depressed 
 
I am severely anxious or depressed 
 
I am extremely anxious or depressed 
 
 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
38/48 
Table 6  
Clot Burden Score for CTA and MRA (46) 
 
No contrast agent filling 
Score 
 
Supraclinoid internal carotid artery 
2 
 
Proximal M1 
2 
Distal M1 
2 
Infraclinoid internal carotid artery 
1 
A1 branch 
1 
M2 branch 
1 
Total score: 10 – Sum 
Total 
 
 
Table 7 
Collateral Score(43) 
 
Category 
Score 
Description 
None 
0 
Absent collaterals 
Poor 
1 
Collaterals filling ≤50% of the occluded territory 
Intermediate 
2 
Collaterals filing >50%, but <100% of the occluded territory 
Good 
3 
Collaterals filling 100% of the occluded territory 
 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
39/48 
Table 8 
Classification pf Infarct in a New Territory (42) 
 
Classification based on size 
Classification based on catheter manipulation 
across territory ostium 
Type I 
≤2 mm diffusion lesion 
(unidentifiable on NCCT) 
Type A 
Catheter was manipulated past the 
ostium of the new territory (e.g. large 
ACA infarct in a patient with an initial 
M1 occlusion): greater likelihood that 
infarct is related to the procedure 
Type II 
>2 mm to ≤ 20 mm lesion 
(potentially difficult to identify on 
CT scan) 
Type B 
Catheter was not manipulated past the 
ostium of the new territory (e.g. left 
PICA infarct in a patient with an initial 
right M1 occlusion): lower likelihood 
that infarct is related to procedure 
Type III 
Large (> 20 mm) infarct 
Glossary: NCCT: Non contrast computed tomography; CTA: Computed tomography angiogram; IAT: intra-
arterial treatment; NIHSS: National Institutes of Health Stroke Scale. 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
40/48 
Table 9 Report of Suspicious Medical Device Adverse Events 
Report of Suspicious Medical Device Adverse Events 
 
Report date: 
Code:            
Report source:  Manufacturer     Distributor     User   Unit name: 
Contact address: 
Post code: 
Contact Tel.: 
 
A. Patient 
 
C.  Medical device 
 
1.  Name 
 
2.  Age 
 
3.  Gender:  
 Male    Female 
 
11.  Product name: 
 
4.  Disease to be treated or expected effect: 
 
12.  Trade name: 
 
B. Overview of adverse event 
 
13.  Registration No.: 
5.  Main conditions of the event: 
14.  Name of the manufacturer: 
 
Address of the manufacturer: 
 
Telephone of the manufacture: 
 
6.  Event occurrence date: 
 
7.  Time of discovery or knowledge: 
15.  Model/specification: 
 
Product number: 
 
Lot number: 
8.  Place where the medical device is actually used: 
 
 Medical institution  
 Home 
 Others (please specify): 
 
15. Operator:  
 Professional  Non-professional 
 Patient 
 
Others 
(specific 
information): 
9.  Consequence 
 
 
Death________________________(specific 
time); 
 
 
Life threatening; 
 
 
Permanent injury to the functional structure of the 
body; 
 
 
May lead to permanent injury to the functional 
structure of the body; 
 
 
Need internal and surgical treatment to avoid the 
17.  Expiration date: 
 
18.  Production date: 
 
19.  Discontinuation date: 
 
20.  Implantation date (if implanted): 
 
21.  Preliminary cause analysis of the event: 

 
 
Version No.: 3.0; Date: August 20, 2019  
41/48 
above permanent injury; 
 
 
Others (details should be given in "Event 
description"). 
 
10.  Event description: (Including at least the device 
usage time, purpose of use, usage basis, usage 
situation, adverse event occurred, impact on the 
victim, treatment measures taken, and the joint use 
of devices) 
 
22.  Preliminary handling of the event: 
 
23.  Reporting progress of the event 
 User has been 
notified 
 Manufacturer has been 
notified 
 Distributor has 
been notified 
 Pharmaceutical 
supervision department 
has been notified 
D.  Relevance evaluation 
 
(1) Was there any reasonable chronological 
sequence between the using of medical 
device and occurred/possible injury event? 
Yes   No  
 
(2) Did the occurred/possible injury event belong 
to the injury type that may be caused by the 
medical device used? Yes  No  Not clear 
 
 
(3) Could the occurred/possible injury event be 
explained by combining the effect of drug 
and/or device, patient’s condition or other 
non-medical device factors? 
Yes       No     Not clear  
 
Evaluation conclusion: Very likely  Possible  
Doubtful □ Undeterminable  
E.  AE assessment 
24.  Evaluation opinions of provincial monitoring 
technical site (attached pages are 
acceptable): 
25.  Evaluation opinions of national monitoring 
technical site (attached pages are 
acceptable): 
Reporter: Physician  
Technician  
 Nurse  
Others  
 
Signature of reporter: 
Prepared 
by 
China 
Food 
and 
Drug 
Administration 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
42/48 
15. Figure 
 
Figure 1  DIRECT-MT Trial Logo 
 
Figure 2 Patient Flow in the Trial 
 
Patient Flow in the Trial 
 
Glossary: CTA: Computed tomography angiogram; IAT: intra-arterial treatment; IVT: intravenous 
thrombolysis; NIHSS: National Institutes of Health Stroke Scale. 
 
 

 
 
Version No.: 3.0; Date: August 20, 2019  
43/48 
16. Appendix 
 
16.1 Study committees 
 
Steering Committee 
Chairman: Prof Liu Jianmin, Changhai Hospital Affiliated to the Second Military Medical University 
Members: Prof Deng Benqiang, Changhai Hospital Affiliated to the Second Military Medical 
University; Prof Charles Majoie, Academisch Medisch Centrum bij de Universitieit van Amsterdam 
(AMC); and Prof Yvo Roos, Academisch Medisch Centrum bij de Universitieit van Amsterdam (AMC) 
 
Data Safety Monitoring Board 
Chairman: Prof. Craig Anderson, The George Institute for Global Health at Peking University Health 
Science Center 
Members: Prof. Miao Zhongrong, Beijing Tiantan Hospital Affiliated to Capital Medical University; 
Prof. He Jia, Department of Health Statistics of Second Military Medical University 
 
Imaging Assessment Committee 
Chairman: Prof. Jianping Lu, Department of Radiology, Changhai Hospital, Naval Medical 
University 
Members:  
Prof. Bing Tian, Department of Radiology, Changhai Hospital, Naval Medical University  
Yongxin Zhang, Department of Neurosurgery, Changhai Hospital, Naval Medical University  
Lei Zhang, Department of Neurosurgery, Changhai Hospital, Naval Medical University 
Hao Wang, Department of Neurology, Linyi People's Hospital 
Zhang Shi, Department of Radiology, Changhai Hospital, Naval Medical University 
Wenjia Peng, Department of Radiology, Changhai Hospital, Naval Medical University 
Xuefeng Zhang, Department of Radiology, Changhai Hospital, Naval Medical University 
Xia Tian, Department of Radiology, Changhai Hospital, Naval Medical University 
Tengfei Zhou, Department of Radiology, Henan Provincial People's Hospital 
Xiaoquan Xu, Department of Radiology, Jiangsu Provincial People's Hospital 
Shenqiang Yan, Department of Neurology, Second Affiliated Hospital; Zhejiang University College 
of Medicine 
Jun Ke, Department of Radiology, First Affiliated Hospital, Soochow University 
Guang Zhang, Department of Neurosurgery, First Affiliated Hospital, Harbin Medical University 
Jun Shi, Core lab, Cardiovascular Chinese research center (CCRC) 
Fang Li, Core lab, Cardiovascular Chinese research center (CCRC) 
Xin Wang, Core lab, Cardiovascular Chinese research center (CCRC) 
Adverse Event Adjudication Committee 
Chairman: Prof. Fang Qi, The First Affiliated Hospital of Soochow University 
Members: Prof. Zhang Yongwei, Changhai Hospital Affiliated to the Second Military Medical 
University; Prof. Fu Jianhui, Huashan Hospital Affiliated to Fudan University 

 
 
Version No.: 3.0; Date: August 20, 2019  
44/48 
 
Outcome Committee 
Chairman: Prof. Li Yansheng, Renji Hospital of Shanghai Jiaotong University School of Medicine 
Members: Prof. Zhang Ping, Changhai Hospital Affiliated to the Second Military Medical University; 
Prof. Zhang Yingying, Huadong Hospital Affiliated to Fudan University. 
 
16.2  DIRECT-MT recommendations of the Steering Committee with regard to type of mechanical 
thrombectomy and use of thrombolytic agents during endovascular procedures. 
 
General 
Inclusion in the trial, randomization, and subsequent endovascular treatment with/without prior IVT 
should be started as soon as possible after presentation in all eligible patients.  
The target time from study randomization to groin puncture will be as fast as possible. All patients 
would be better to undergo groin puncture within a median of 60 minutes after randomization. 
 
Neuroimaging 
Neuroimaging studies to assess vessel patency should be done before or simultaneously with 
treatment with intravenous (IV) alteplase, in order not to lose time and brain. We aim to not cause 
any delay prior to intra-arterial treatment, by infusion of IV alteplase. 
 
Additional thrombolytic agents, dose and type 
If deemed indicated by the interventionist, local application (intra-arterial) alteplase is allowed in any 
of the patients included in the DIRECT-MT. 
Patients who have been pre-treated with IV alteplase should not receive more than 30 mg alteplase 
during intra-arterial treatment. The steering committee recommends that the alteplase is delivered 
in shots of 5 mg, in 5-10 minutes time intervals. In individual cases, an equivalent dose of 400,000 
U urokinase, delivered in shots of 50.000 - 100.000 U, in 5-10 minutes time intervals, is also accepted 
as escape medication. Vessel patency should be checked after each shot. 
 
Type of mechanical thrombectomy device(s) 
All stent retriever and aspiration devices for IAT, which are approved for this purpose by CFDA, and 
have been approved for use in the study by the steering committee are allowed in the trial as a first 
line of defense and are listed below: 
Device name 
Manufacturer 
Description 
Solitaire 
Medtronic / Covidien 
Retrievable stent 
Trevo  
Stryker 
Retrievable stent 
Revive  
Johnson & Johnson/ Cerenovus 
Retrievable stent 

 
 
Version No.: 3.0; Date: August 20, 2019  
45/48 
A second device is allowed as a second option, when the first device has failed according to the 
interventionist. The further choice of the particular device for a certain patient is left to the discretion 
of the interventionist. 
 
16.3  Imaging requirements 
 
16.3.1  Minimum baseline imaging requirements 
When 
1)  Before randomization, a NCCT and CTA should be performed to assess eligibility for the study. 
How 
1. 
Pre-randomization NCCT: 
1. The thickness of the NCCT scanning layer is recommended to be 5 mm, and 5-8 mm is 
also acceptable. 
2. The NCCT study should include the whole head. 
2. 
Pre-randomization CTA: 
1. The CTA study should cover the whole area from the aortic arch to the vertex, and 
intracranial part only is also acceptable. 
2. The CTA study should include thin slices (maximum of 1.0 mm) 
3. The CTA study should include the following reconstructions 
i. 
Axial maximum intensity projection (MIP), 
1. MIP slab thickness: 25 mm 
2. Overlap: 5 mm 
ii. 
Coronal MIP 
1. 
MIP slab thickness: 25 mm 
2. 
Overlap: 5 mm 
3. 
After acquisition 
1. All images (both NCCT and CTA) should be saved to the DICOM format 
2. All available series should be sent to the core lab for assessment, including thin slice 
series (for thrombus assessment). 
16.3.2  Intervention-related angiographic imaging 
When 
1) Before the intervention complete AP and Lateral angiograms (of whole head and including 

 
 
Version No.: 3.0; Date: August 20, 2019  
46/48 
venous phase) should be performed to evaluate the site of vessel occlusion, extent of thrombus, 
territories involved, concomitant pathologies and to assess collateral flow.  
2) After each passage of a mechanical or aspirational device, a control angiogram should be 
performed. 
3) After each bolus of (a rescue) thrombolytic agent, a control angiogram should be performed. 
4) At the end of the procedure complete AP and Lateral angiograms (of whole head and including 
venous phase) should be repeated. Without these complete runs, optimal TICI scoring is not 
possible 
 
How 
Pre-intervention and end-of-procedure angiogram: 
a. Angiograms should be performed through the guiding catheter 
b. Baseline and final AP views and lateral views of the intracranial arteries are 
mandatory. Both are required to assess reperfusion after the procedure. 
c. 
Baseline and final angiograms should include both the arterial and venous phases 
of the injection to evaluate the collateral pathways and perfusion of the distal 
vascular bed. 
d. Baseline and final angiograms should include the internal carotid artery feeding the 
target vessel as demonstrated on CTA. 
e. Baseline and final angiograms should include the common carotid and internal 
carotid artery in case of occlusion, dissection or severe stenosis in the carotid 
feeding the target vessel as demonstrated on CTA. 
f. 
Angiograms should be performed via the guiding catheter with the same catheter 
position and same views before and after the procedures to adequately assess the 
results of therapy. 
After each device placement: 
g. A non-contrast radiograph should be obtained 
h. At least one view at the discretion of the interventionalist 
After each passage of mechanical or aspirational device or bolus of (rescue) thrombolytic 
agent : 
i. 
Angiograms should be performed through the guiding catheter 
j. 
At least one view, at the discretion of the interventionalist. 
After the procedure 
k. 
Complete series of the angiograms and microcatheter injections (when performed) 

 
 
Version No.: 3.0; Date: August 20, 2019  
47/48 
should be saved according to the DICOM standard. 
l. 
All series should be forwarded to the imaging assessment committee. 
 
16.3.3  Minimum follow-up imaging requirements 
 
When 
1) 24-72 hours after undergoing endovascular treatment, a NCCT and CTA should be performed 
to assess treatment efficacy. 
2) 5-7 days after undergoing endovascular treatment, or before discharge a NCCT should be 
performed to assess final lesion volume and potential hemorrhages complications. 
3) If clinically required (i.e. in cases of clinical deterioration of the patient) additional imaging as 
needed, at the discretion of the treating physician is acquired. 
 
How 
24-72 hours NCCT: 
1. The thickness of the NCCT scanning layer is recommended to be 5 mm, and 5-8 mm 
is also acceptable. 
2. The NCCT study should include the whole head. 
24-72 hours CTA: 
3. The CTA study should cover the whole area from the aortic arch to the vertex, and 
intracranial part only is also acceptable. 
4. The CTA study should include thin slices (maximum of 1.0 mm) 
5. The CTA study should include the following reconstructions 
i. 
Axial maximum intensity projection (MIP), 
1. MIP slab thickness: 25 mm 
2. Overlap: 5 mm 
ii. 
Coronal MIP 
1. MIP slab thickness: 25 mm 
2. Overlap: 5 mm 
5-7 days NCCT (or before discharge) 
6. The NCCT study should contain both thick (5mm) and thin slices (maximum of 2.5mm). 
7. The NCCT study should include the whole head. 
8. 
In addition, clinically required imaging is at the discretion of the treating physician. 

 
 
Version No.: 3.0; Date: August 20, 2019  
48/48 
9. 
After acquisition, all images (NCCT, CTA, and additional imaging) should be saved 
to the DICOM file format 
10. All available series should be sent to the core lab for assessment, including thin slice 
series (for thrombus assessment).