Ischemic StrokeDIRECT-MTNCT03469206
Direct Intra-arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals
A study testing intra-arterial thrombectomy and Intravenous thrombolysis in people with Ischemic Stroke and Large Vessel Occlusion, run by Changhai Hospital at 1 site in China.
Trial summary
Background: Intravenous thrombolysis (IVT) combined with mechanical thrombectomy (MT) has been proven safe and effective in patients with acute ischemic stroke (AIS) of anterior circulation large vessel occlusion (LVO). Despite recanalization, a considerable proportion of patients do not recover. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke, Large Vessel Occlusion, Thrombectomy
- What is being tested?
- intra-arterial thrombectomy and Intravenous thrombolysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 656 participants
- Where
- 1 siteChina
- Study dates
- 21 Feb 2018to 26 Oct 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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),
- a score of at least 2 on the NIH Stroke Scale,
- age of 18 years or older,
- written informed consent.
Who cannot join
- - 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.:
- arterial blood pressure exceeding 185/110 mmHg
- blood glucose less than 2.7 or over 22.2 mmol/L
- cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging
- serious head trauma in the previous 3 months
Show all 13Show fewer
- 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 x 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Background: Intravenous thrombolysis (IVT) combined with mechanical thrombectomy (MT) has been proven safe and effective in patients with acute ischemic stroke (AIS) of anterior circulation large vessel occlusion (LVO). Despite recanalization, a considerable proportion of patients do not recover. The incidence of symptomatic intracerebral hemorrhage (sICH) was similar between combined IVT plus MT and IVT, suggesting that this complication could not be attributed to the MT, but rather to pre-treatment with IVT. Meanwhile, the incidence of intracranial atherosclerosis stenosis (ICAS) is higher in Asians. It is not clear whether patients with ICAS benefit from pretreatment with alteplase or not and how ICAS modifies treatment effect.
Objective: To assess whether direct MT is non-inferior compared to combined IVT plus MT in patients with AIS due to an anterior circulation LVO, and to assess treatment effect modification by presence of ICAD.
Read more
Study design: This is a parallel group, RCT of direct MT compared to combined IVT plus MT, using a non-inferiority design. The trial has observer blinded assessment of the primary outcome and of neuro-imaging at baseline and follow up. The trial will be executed in collaboration with MRCLEAN NO-IV investigators.
Study population: Patients with AIS of anterior circulation VLO confirmed 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.
Main outcomes: The full distribution of the mRS at 3 months. Secondary outcomes: 1. death within 90 +/- 14 days; 2. pre-interventional reperfusion assessed on first intracranial DSA; 3. eTICI19 score on final angiography of MT; 4. score on the NIHSS at 24 +/- 6 hours and 5-7 days, or at discharge; 5. recanalization rate at 24-72h by CTA; 6. Final lesion volume at 5-7 days on NCCT20; 7. score on the EuroQoL 5-dimensions 5-level (EQ5D-5L)21 and Barthel index22 at 90 +/- 14 days; 8. dichotomous clinical outcome on the mRS at 90 +/- 14 days.
Read the detailed description
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: Mechanical thrombectomy (MT) by means of retrievable stents has been proven safe and effective in patients with acute ischemic stroke (AIS) 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 MT. 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 MT, but rather to pre-treatment with IVT. Therefore, the investigators hypothesize that direct MT may lead to a 8% absolute increase in good outcome compared to MT preceded by IVT.
Objective: To assess whether direct MT is non-inferior compared to combined IVT plus MT in patients with AIS due to an anterior circulation LVO, and to assess treatment effect modification by presence of ICAD.
Study design: This is a multicenter, prospective, open label parallel group trial with blinded outcome assessment (PROBE design) assessing non-inferiority of direct MT compared to combined IVT plus MT.
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 carotid artery or middle M1/proximal M2) cerebral artery confirmed by CTA,
- CT or MRI ruling out intracranial hemorrhage,
- eligible for IVT and MT (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. 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.:
- arterial blood pressure exceeding 185/110 mmHg
- blood glucose less than 2.7 or over 22.2 mmol/L
- cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of 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 x 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.
Intervention: The intervention group will undergo immediate MT 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 MT using a stent retriever. the investigators strive to reduce delays associated with IVT administration to a minimum to adequately assess the effect of IVT itself with MT.
Main study parameters/outcomes: The primary outcome is the score on the modified Rankin Scale assessed blindly at 90 (+/- 14) days. An common odds ratio, adjusted for the prognostic factors (age, NIHSS, collateral score), representing the shift on the 6-category mRS scale measured at 3 months, estimated with ordinal logistic regression, will be the primary effect parameter.
Secondary outcomes: 1. death within 90 +/- 14 days; 2. pre-interventional reperfusion assessed on first intracranial DSA; 3. eTICI19 score on final angiography of MT; 4. score on the NIHSS at 24 +/- 6 hours and 5-7 days, or at discharge; 5. recanalization rate at 24-72h by CTA; 6. Final lesion volume at 5-7 days on NCCT20; 7. score on the EuroQoL 5-dimensions 5-level (EQ5D-5L)21 and Barthel index22 at 90 +/- 14 days; 8. dichotomous clinical outcome on the mRS at 90 +/- 14 days.
- Conditions
- Ischemic Stroke, Large Vessel Occlusion, Thrombectomy, Thrombosis, Alteplase
- Being tested
- intra-arterial thrombectomy, Intravenous thrombolysis
- Medical subject headings
- Ischemic Stroke, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intra-arterial thrombectomyProcedure or surgery
It is the emergency surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi (blood clots)
Intravenous thrombolysisDrug
alteplase is used in the intravenous thrombolysis. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.
| Study group | Role | What they receive |
|---|---|---|
| Direct MT | Sham comparator | Direct mechanical thrombectomy (MT) with no intravenous thrombolysis Receives: Procedure: intra-arterial thrombectomy |
| IVT combine with MT | Active comparator | Intravenous thrombolysis before mechanical thrombectomy Receives: Procedure: intra-arterial thrombectomy; Drug: Intravenous thrombolysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
mRS (the modified Rankin Scale)
The mRS is an ordinal hierarchical scale ranging from 0 to 5, with higher scores indicating more severe disability.
Measured: 3 months after procedure
Secondary outcomes (5)
eTICI score (Extended Treatment In Cerebral Ischemia)
The eTICI is an ordinal hierarchical scale ranging from 0 to 3, with higher scores indicating better antegrade reperfusion of the previously occluded target artery ischemic territory.
Measured: Immediately after procedure
NIHSS (The National Institutes of Health Stroke Scale)
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.
Measured: at 24 hours and 5-7 days
Recanalization rate
Recanalization rate at 24-48 hours after intra-arterial thrombectomy, assessed with CT angiography
Measured: at 24-48 hours after intra-arterial thrombectomy
Final infarct volume
Final infarct volume will be assessed with the use of an automated, validated algorithm.
Measured: at 5-7 days
sICH (symptomatic intracranial hemorrhage) rate
SICH means any hemorrhage with neurological deterioration, as indicated by an NIHSS score that was higher by ≥4 points than the value at baseline or the lowest value in the first 7 days or any hemorrhage leading to death.
Measured: 7 days after intra-arterial thrombectomy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2018
- Study start21 Feb 2018
- Primary completion20 Oct 2019
- Study completion26 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 656 participants (actual)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Family Planning Commission, P.R.China, Wu Jieping Medical Foundation, Cardiovascular Chinese Research Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Responsible party
- Principal investigator, Jian-min Liu, Changhai Hospital
- Investigators
- Jianmin Liu, M.D., Principal investigator, Neurosurgery Department of Changhai HospitalBenqiang Deng, M.D., Principal investigator, Neurology Department of Changhai HospitalCharles Majoie, M.D., Principal investigator, Radiology Department of Academic Medical Center AmsterdamYvo Roos, M.D., Principal investigator, Neurology Department of Academic Medical Center Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03469206
- Sponsor's protocol ID
- DIRECT MT
- Acronym
- DIRECT-MT
- Status last verified
- Oct 2019
- First submitted
- 28 Feb 2018
- Last updated
- 29 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen R, Luo J, Yu Y, Hua W, Huyan M, Zhang Y, Zhang H, Liu J, Zhang L, Yang P. Interaction of basal ganglia infarction with bridging therapy vs mechanical thrombectomy on parenchymal hemorrhage: A secondary analysis of the DIRECT-MT trial. J Clin Neurosci. 2026 Jul;149:112017. doi: 10.1016/j.jocn.2026.112017. Epub 2026 Apr 8.
PubMed 41955857Chen R, Hua W, Zhang Y, Zhang Y, Zhang H, Zhang Y, Liu J, Yang P, Zhang X, Zhang L. Asymptomatic Hemorrhagic Events and Functional Outcomes in Acute Stroke: A Secondary Analysis of the DIRECT-MI Randomized Clinical Trial. JAMA Netw Open. 2025 Mar 3;8(3):e252411. doi: 10.1001/jamanetworkopen.2025.2411.
PubMed 40152857Wu Q, Chen X, Wu Y, Ma L, Chen Y, Zhang W, Deng R, Liu J, Zhang L, Li Z, Xing P, Zhang Y, Yang P, Liu Y, Xie P, Wang L, Chen S, Liu J. Impact of Body Mass Index on Outcome of Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke in China: A Post Hoc Analysis of DIRECT-MT Trial. Cerebrovasc Dis. 2025;54(6):873-884. doi: 10.1159/000544907. Epub 2025 Mar 3.
PubMed 40031887Li Z, Ma H, Li B, Zhang L, Zhang Y, Xing P, Zhang Y, Zhang X, Zhou Y, Huang Q, Li Q, Zuo Q, Ye X, Liu J, Qureshi AI, Chen W, Yang P; DIRECT-MT Investigators. Impact of anesthesia modalities on functional outcome of mechanical thrombectomy in patients with acute ischemic stroke: a subgroup analysis of DIRECT-MT trial. Eur J Med Res. 2023 Jul 10;28(1):228. doi: 10.1186/s40001-023-01171-x.
PubMed 37430361Cao J, Xing P, Zhu X, Chen R, Shao H, Xuan J, Jiang T, Yang P, Zhang Y, Li Z, Chen W, Li T, Wang S, Lou M, Peng Y, Liu J. Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy: A subgroup analysis of a randomized clinical trial (DIRECT-MT). Front Neurol. 2022 Nov 24;13:1013819. doi: 10.3389/fneur.2022.1013819. eCollection 2022.
PubMed 36504640Xiaoxi Z, Xuan Z, Lei Z, Zifu L, Pengfei X, Hongjian S, Yongxin Z, Weilong H, Yihan Z, Dongwei D, Qiang L, Rui Z, Qinghai H, Yi X, Song L, Anderson CS, Jianmin L, Yongwei Z, Pengfei Y. Baseline blood pressure does not modify the effect of intravenous thrombolysis in successfully revascularized patients. Front Neurol. 2022 Sep 12;13:984599. doi: 10.3389/fneur.2022.984599. eCollection 2022.
PubMed 36172030Zhou Y, Wang Z, Ospel J, Goyal M, McDonough R, Yang P, Zhang Y, Zhang L, Ye X, Wei F, Su D, Lu H, Que X, Han H, Li T, Liu J; DIRECT-MT investigators. Effect of Admission Hyperglycemia on Safety and Efficacy of Intravenous Alteplase Before Thrombectomy in Ischemic Stroke: Post-hoc Analysis of the DIRECT-MT trial. Neurotherapeutics. 2022 Oct;19(6):1932-1941. doi: 10.1007/s13311-022-01281-0. Epub 2022 Sep 23.
PubMed 36151441Zhang M, Xing P, Tang J, Shi L, Yang P, Zhang Y, Zhang L, Peng Y, Liu S, Zhang L, Fu J, Liu J; DIRECT-MT Investigators. Predictors and outcome of early neurological deterioration after endovascular thrombectomy: a secondary analysis of the DIRECT-MT trial. J Neurointerv Surg. 2023 Sep;15(e1):e9-e16. doi: 10.1136/neurintsurg-2022-018976. Epub 2022 Jun 10.
PubMed 35688618Zhou Y, Zhang L, Ospel J, Goyal M, McDonough R, Xing P, Li Z, Zhang X, Zhang Y, Zhang Y, Hong B, Xu Y, Huang Q, Li Q, Yu Y, Zuo Q, Ye X, Yang P, Liu J; DIRECT-MT Investigators. Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial. Stroke. 2022 Jun;53(6):1828-1836. doi: 10.1161/STROKEAHA.121.037061. Epub 2022 Mar 4.
PubMed 35240861Li H, Huang J, Ye S, Chen H, Yuan L, Liao G, Du W, Li C, Fang L, Liu S, Yang P, Zhang Y, Xing P, Zhang X, Ye X, Peng Y, Cao J, Zhang L, Yang Z, Liu J; DIRECT-MT investigators. Predictors of mortality in acute ischemic stroke treated with endovascular thrombectomy despite successful reperfusion: subgroup analysis of a multicentre randomised clinical trial. BMJ Open. 2022 Mar 1;12(3):e053765. doi: 10.1136/bmjopen-2021-053765.
PubMed 35232782Zhang P, Shen HJ, Chen L, Zhu X, Zhang MM, Jiang Y, Yang PF, Zhang L, Xing PF, Ye XF, Lou M, Yin CG, Deng BQ, Wu T, Zhang YW, Liu JM. Patient-Reported Anxiety/Depression After Endovascular Thrombectomy: A post-hoc Analysis of Direct-MT Trial. Front Neurol. 2022 Feb 9;13:811629. doi: 10.3389/fneur.2022.811629. eCollection 2022.
PubMed 35222248Xing P, Zhang X, Shen H, Shen F, Zhang L, Li Z, Zhang Y, Hong B, Shi H, Han H, Ye X, Zhang Y, Yang P, Liu J; DIRECT-MT investigators. Effect of stroke etiology on endovascular thrombectomy with or without intravenous alteplase: a subgroup analysis of DIRECT-MT. J Neurointerv Surg. 2022 Dec;14(12):1200-1206. doi: 10.1136/neurintsurg-2021-018275. Epub 2022 Jan 11.
PubMed 35017204Zhou Y, Xing P, Li Z, Zhang X, Zhang L, Zhang Y, Zhang Y, Hong B, Xu Y, Huang Q, Li Q, Zhao K, Zou C, Yu Y, Zuo Q, Liu S, Zhang L, Majoie CBLM, Roos YBWEM, Treurniet KM, Ye X, Peng Y, Yang P, Liu J; DIRECT-MT Investigators. Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT. Stroke. 2022 Jan;53(1):7-16. doi: 10.1161/STROKEAHA.121.035267. Epub 2021 Dec 17.
PubMed 34915738Tian B, Tian X, Shi Z, Peng W, Zhang X, Yang P, Li Z, Zhang X, Lou M, Yin C, Zhang Y, Lu J, Liu J; DIRECT-MT Investigators. Clinical and Imaging Indicators of Hemorrhagic Transformation in Acute Ischemic Stroke After Endovascular Thrombectomy. Stroke. 2022 May;53(5):1674-1681. doi: 10.1161/STROKEAHA.121.035425. Epub 2021 Dec 7.
PubMed 34872341Geng C, Li SD, Zhang DD, Ma L, Liu GW, Jiao LQ, Liu JM, Chen WH, Zhu WS, Wen CM, Peng B. Endovascular Thrombectomy Versus Bridging Thrombolysis: Real-World Efficacy and Safety Analysis Based on a Nationwide Registry Study. J Am Heart Assoc. 2021 Feb 2;10(3):e018003. doi: 10.1161/JAHA.120.018003. Epub 2021 Jan 26.
PubMed 33496186
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03469206
- Acronym / sponsor ID
- DIRECT-MT / DIRECT MT
- Conditions
- Ischemic Stroke, Large Vessel Occlusion, Thrombectomy, Thrombosis, Alteplase
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 656 participants (actual)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Collaborators
- National Health and Family Planning Commission, P.R.China, Wu Jieping Medical Foundation, Cardiovascular Chinese Research Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 20 Oct 2019 (actual)
- Study completion
- 26 Oct 2019 (actual)
- First posted
- 19 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Intravenous thrombolysis (IVT) combined with mechanical thrombectomy (MT) has been proven safe and effective in patients with acute ischemic stroke (AIS) of anterior circulation large vessel occlusion (LVO). Despite recanalization, a considerable proportion of patients do not recover. The incidence of symptomatic intracerebral hemorrhage (sICH) was similar between combined IVT plus MT and IVT, suggesting that this complication could not be attributed to the MT, but rather to pre-treatment with IVT. Meanwhile, the incidence of intracranial atherosclerosis stenosis (ICAS) is higher in Asians. It is not clear whether patients with ICAS benefit from pretreatment with alteplase or not and how ICAS modifies treatment effect.
Objective: To assess whether direct MT is non-inferior compared to combined IVT plus MT in patients with AIS due to an anterior circulation LVO, and to assess treatment effect modification by presence of ICAD.
Study design: This is a parallel group, RCT of direct MT compared to combined IVT plus MT, using a non-inferiority design. The trial has observer blinded assessment of the primary outcome and of neuro-imaging at baseline and follow up. The trial will be executed in collaboration with MRCLEAN NO-IV investigators.
Study population: Patients with AIS of anterior circulation VLO confirmed 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.
Main outcomes: The full distribution of the mRS at 3 months. Secondary outcomes: 1. death within 90 +/- 14 days; 2. pre-interventional reperfusion assessed on first intracranial DSA; 3. eTICI19 score on final angiography of MT; 4. score on the NIHSS at 24 +/- 6 hours and 5-7 days, or at discharge; 5. recanalization rate at 24-72h by CTA; 6. Final lesion volume at 5-7 days on NCCT20; 7. score on the EuroQoL 5-dimensions 5-level (EQ5D-5L)21 and Barthel index22 at 90 +/- 14 days; 8. dichotomous clinical outcome on the mRS at 90 +/- 14 days.
Detailed description
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: Mechanical thrombectomy (MT) by means of retrievable stents has been proven safe and effective in patients with acute ischemic stroke (AIS) 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 MT. 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 MT, but rather to pre-treatment with IVT. Therefore, the investigators hypothesize that direct MT may lead to a 8% absolute increase in good outcome compared to MT preceded by IVT.
Objective: To assess whether direct MT is non-inferior compared to combined IVT plus MT in patients with AIS due to an anterior circulation LVO, and to assess treatment effect modification by presence of ICAD.
Study design: This is a multicenter, prospective, open label parallel group trial with blinded outcome assessment (PROBE design) assessing non-inferiority of direct MT compared to combined IVT plus MT.
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 carotid artery or middle M1/proximal M2) cerebral artery confirmed by CTA,
- CT or MRI ruling out intracranial hemorrhage,
- eligible for IVT and MT (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. 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.:
- arterial blood pressure exceeding 185/110 mmHg
- blood glucose less than 2.7 or over 22.2 mmol/L
- cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of 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 x 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.
Intervention: The intervention group will undergo immediate MT 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 MT using a stent retriever. the investigators strive to reduce delays associated with IVT administration to a minimum to adequately assess the effect of IVT itself with MT.
Main study parameters/outcomes: The primary outcome is the score on the modified Rankin Scale assessed blindly at 90 (+/- 14) days. An common odds ratio, adjusted for the prognostic factors (age, NIHSS, collateral score), representing the shift on the 6-category mRS scale measured at 3 months, estimated with ordinal logistic regression, will be the primary effect parameter.
Secondary outcomes: 1. death within 90 +/- 14 days; 2. pre-interventional reperfusion assessed on first intracranial DSA; 3. eTICI19 score on final angiography of MT; 4. score on the NIHSS at 24 +/- 6 hours and 5-7 days, or at discharge; 5. recanalization rate at 24-72h by CTA; 6. Final lesion volume at 5-7 days on NCCT20; 7. score on the EuroQoL 5-dimensions 5-level (EQ5D-5L)21 and Barthel index22 at 90 +/- 14 days; 8. dichotomous clinical outcome on the mRS at 90 +/- 14 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Direct MT | Sham comparator | Procedure: intra-arterial thrombectomyDirect mechanical thrombectomy (MT) with no intravenous thrombolysis |
| IVT combine with MT | Active comparator | Procedure: intra-arterial thrombectomy, Drug: Intravenous thrombolysisIntravenous thrombolysis before mechanical thrombectomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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),
- a score of at least 2 on the NIH Stroke Scale,
Key exclusion criteria (13 listed)
- - 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.:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intra-arterial thrombectomyIt is the emergency surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi (blood clots) | Procedure or surgery | Direct MT, IVT combine with MT |
| Intravenous thrombolysisalteplase is used in the intravenous thrombolysis. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. | Drug | IVT combine with MT |
Primary outcome
mRS (the modified Rankin Scale)
Time frame: 3 months after procedure
The mRS is an ordinal hierarchical scale ranging from 0 to 5, with higher scores indicating more severe disability.
5 secondary outcomes
eTICI score (Extended Treatment In Cerebral Ischemia)
Time frame: Immediately after procedure
NIHSS (The National Institutes of Health Stroke Scale)
Time frame: at 24 hours and 5-7 days
Recanalization rate
Time frame: at 24-48 hours after intra-arterial thrombectomy
Final infarct volume
Time frame: at 5-7 days
sICH (symptomatic intracranial hemorrhage) rate
Time frame: 7 days after intra-arterial thrombectomy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
- Derived from this study: PubMed 41955857Chen R, Luo J, Yu Y, Hua W, Huyan M, Zhang Y, Zhang H, Liu J, Zhang L, Yang P. Interaction of basal ganglia infarction with bridging therapy vs mechanical thrombectomy on parenchymal hemorrhage: A secondary analysis of the DIRECT-MT trial. J Clin Neurosci. 2026 Jul;149:112017. doi: 10.1016/j.jocn.2026.112017. Epub 2026 Apr 8.
- Derived from this study: PubMed 40152857Chen R, Hua W, Zhang Y, Zhang Y, Zhang H, Zhang Y, Liu J, Yang P, Zhang X, Zhang L. Asymptomatic Hemorrhagic Events and Functional Outcomes in Acute Stroke: A Secondary Analysis of the DIRECT-MI Randomized Clinical Trial. JAMA Netw Open. 2025 Mar 3;8(3):e252411. doi: 10.1001/jamanetworkopen.2025.2411.
- Derived from this study: PubMed 40031887Wu Q, Chen X, Wu Y, Ma L, Chen Y, Zhang W, Deng R, Liu J, Zhang L, Li Z, Xing P, Zhang Y, Yang P, Liu Y, Xie P, Wang L, Chen S, Liu J. Impact of Body Mass Index on Outcome of Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke in China: A Post Hoc Analysis of DIRECT-MT Trial. Cerebrovasc Dis. 2025;54(6):873-884. doi: 10.1159/000544907. Epub 2025 Mar 3.
- Derived from this study: PubMed 37430361Li Z, Ma H, Li B, Zhang L, Zhang Y, Xing P, Zhang Y, Zhang X, Zhou Y, Huang Q, Li Q, Zuo Q, Ye X, Liu J, Qureshi AI, Chen W, Yang P; DIRECT-MT Investigators. Impact of anesthesia modalities on functional outcome of mechanical thrombectomy in patients with acute ischemic stroke: a subgroup analysis of DIRECT-MT trial. Eur J Med Res. 2023 Jul 10;28(1):228. doi: 10.1186/s40001-023-01171-x.
- Derived from this study: PubMed 36504640Cao J, Xing P, Zhu X, Chen R, Shao H, Xuan J, Jiang T, Yang P, Zhang Y, Li Z, Chen W, Li T, Wang S, Lou M, Peng Y, Liu J. Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy: A subgroup analysis of a randomized clinical trial (DIRECT-MT). Front Neurol. 2022 Nov 24;13:1013819. doi: 10.3389/fneur.2022.1013819. eCollection 2022.
- Derived from this study: PubMed 36172030Xiaoxi Z, Xuan Z, Lei Z, Zifu L, Pengfei X, Hongjian S, Yongxin Z, Weilong H, Yihan Z, Dongwei D, Qiang L, Rui Z, Qinghai H, Yi X, Song L, Anderson CS, Jianmin L, Yongwei Z, Pengfei Y. Baseline blood pressure does not modify the effect of intravenous thrombolysis in successfully revascularized patients. Front Neurol. 2022 Sep 12;13:984599. doi: 10.3389/fneur.2022.984599. eCollection 2022.
- Derived from this study: PubMed 36151441Zhou Y, Wang Z, Ospel J, Goyal M, McDonough R, Yang P, Zhang Y, Zhang L, Ye X, Wei F, Su D, Lu H, Que X, Han H, Li T, Liu J; DIRECT-MT investigators. Effect of Admission Hyperglycemia on Safety and Efficacy of Intravenous Alteplase Before Thrombectomy in Ischemic Stroke: Post-hoc Analysis of the DIRECT-MT trial. Neurotherapeutics. 2022 Oct;19(6):1932-1941. doi: 10.1007/s13311-022-01281-0. Epub 2022 Sep 23.
- Derived from this study: PubMed 35688618Zhang M, Xing P, Tang J, Shi L, Yang P, Zhang Y, Zhang L, Peng Y, Liu S, Zhang L, Fu J, Liu J; DIRECT-MT Investigators. Predictors and outcome of early neurological deterioration after endovascular thrombectomy: a secondary analysis of the DIRECT-MT trial. J Neurointerv Surg. 2023 Sep;15(e1):e9-e16. doi: 10.1136/neurintsurg-2022-018976. Epub 2022 Jun 10.
- Derived from this study: PubMed 35240861Zhou Y, Zhang L, Ospel J, Goyal M, McDonough R, Xing P, Li Z, Zhang X, Zhang Y, Zhang Y, Hong B, Xu Y, Huang Q, Li Q, Yu Y, Zuo Q, Ye X, Yang P, Liu J; DIRECT-MT Investigators. Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial. Stroke. 2022 Jun;53(6):1828-1836. doi: 10.1161/STROKEAHA.121.037061. Epub 2022 Mar 4.
- Derived from this study: PubMed 35232782Li H, Huang J, Ye S, Chen H, Yuan L, Liao G, Du W, Li C, Fang L, Liu S, Yang P, Zhang Y, Xing P, Zhang X, Ye X, Peng Y, Cao J, Zhang L, Yang Z, Liu J; DIRECT-MT investigators. Predictors of mortality in acute ischemic stroke treated with endovascular thrombectomy despite successful reperfusion: subgroup analysis of a multicentre randomised clinical trial. BMJ Open. 2022 Mar 1;12(3):e053765. doi: 10.1136/bmjopen-2021-053765.
- Derived from this study: PubMed 35222248Zhang P, Shen HJ, Chen L, Zhu X, Zhang MM, Jiang Y, Yang PF, Zhang L, Xing PF, Ye XF, Lou M, Yin CG, Deng BQ, Wu T, Zhang YW, Liu JM. Patient-Reported Anxiety/Depression After Endovascular Thrombectomy: A post-hoc Analysis of Direct-MT Trial. Front Neurol. 2022 Feb 9;13:811629. doi: 10.3389/fneur.2022.811629. eCollection 2022.
- Derived from this study: PubMed 35017204Xing P, Zhang X, Shen H, Shen F, Zhang L, Li Z, Zhang Y, Hong B, Shi H, Han H, Ye X, Zhang Y, Yang P, Liu J; DIRECT-MT investigators. Effect of stroke etiology on endovascular thrombectomy with or without intravenous alteplase: a subgroup analysis of DIRECT-MT. J Neurointerv Surg. 2022 Dec;14(12):1200-1206. doi: 10.1136/neurintsurg-2021-018275. Epub 2022 Jan 11.
- DIRECT-MT websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jianmin Liu, M.D. principal investigator
Neurosurgery Department of Changhai Hospital
Benqiang Deng, M.D. principal investigator
Neurology Department of Changhai Hospital
Charles Majoie, M.D. principal investigator
Radiology Department of Academic Medical Center Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intra-arterial thrombectomy and Intravenous thrombolysis in people with Ischemic Stroke and Large Vessel Occlusion, run by Changhai Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mRS (the modified Rankin Scale) (time frame: 3 months after procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03469206, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2019.