Direct Intra-arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals

NCT03469206 | Completed DMC

• 1 other identifier: DIRECT MT
• Study Type: interventional
• Target: 656
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Ischemic Stroke; Large Vessel Occlusion; Thrombectomy; Thrombosis; Alteplase

Outcome Measures

Primary Outcomes (1)

• mRS (the modified Rankin Scale)

  The mRS is an ordinal hierarchical scale ranging from 0 to 5, with higher scores indicating more severe disability.

  3 months after procedure

Secondary Outcomes (5)

• eTICI score (Extended Treatment In Cerebral Ischemia)

  Immediately after procedure

• NIHSS (The National Institutes of Health Stroke Scale)

  at 24 hours and 5-7 days

• Recanalization rate

  at 24-48 hours after intra-arterial thrombectomy

• Final infarct volume

  at 5-7 days

• sICH (symptomatic intracranial hemorrhage) rate

  7 days after intra-arterial thrombectomy

Study Arms (2)

Direct MT

SHAM COMPARATOR

Direct mechanical thrombectomy (MT) with no intravenous thrombolysis

Procedure: intra-arterial thrombectomy

IVT combine with MT

ACTIVE COMPARATOR

Intravenous thrombolysis before mechanical thrombectomy

Procedure: intra-arterial thrombectomy; Drug: Intravenous thrombolysis

Interventions

intra-arterial thrombectomy PROCEDURE

It is the emergency surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi (blood clots)

Direct MT; IVT combine with MT

Intravenous thrombolysis DRUG

alteplase is used in the intravenous thrombolysis. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.

IVT combine with MT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Changhai Hospital: lead
• National Health and Family Planning Commission, P.R.China: collaborator
• Wu Jieping Medical Foundation: collaborator
• Cardiovascular Chinese Research Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (14)

• Chen 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.

  PMID: 40152857 DERIVED

• Li 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.

  PMID: 37430361 DERIVED

• Cao 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.

  PMID: 36504640 DERIVED

• Xiaoxi 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.

  PMID: 36172030 DERIVED

• Zhou 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.

  PMID: 36151441 DERIVED

• Zhang 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.

  PMID: 35688618 DERIVED

• Zhou 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.

  PMID: 35240861 DERIVED

• Li 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.

  PMID: 35232782 DERIVED

• Zhang 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.

  PMID: 35222248 DERIVED

• Xing 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.

  PMID: 35017204 DERIVED

• Zhou 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.

  PMID: 34915738 DERIVED

• Tian 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.

  PMID: 34872341 DERIVED

• Geng 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.

  PMID: 33496186 DERIVED

• Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, Yin C, Liu S, Wang P, Fang Q, Shi H, Yang J, Wen C, Li C, Jiang C, Sun J, Yue X, Lou M, Zhang M, Shu H, Sun D, Liang H, Li T, Guo F, Ke K, Yuan H, Wang G, Yang W, Shi H, Li T, Li Z, Xing P, Zhang P, Zhou Y, Wang H, Xu Y, Huang Q, Wu T, Zhao R, Li Q, Fang Y, Wang L, Lu J, Li Y, Fu J, Zhong X, Wang Y, Wang L, Goyal M, Dippel DWJ, Hong B, Deng B, Roos YBWEM, Majoie CBLM, Liu J; DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 21;382(21):1981-1993. doi: 10.1056/NEJMoa2001123. Epub 2020 May 6.

  PMID: 32374959 DERIVED

Related Links

• DIRECT-MT website

MeSH Terms

Conditions

Ischemic Stroke; Thrombosis

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis

Study Officials

• Jianmin Liu, M.D.

  Neurosurgery Department of Changhai Hospital

  PRINCIPAL INVESTIGATOR

• Benqiang Deng, M.D.

  Neurology Department of Changhai Hospital

  PRINCIPAL INVESTIGATOR

• Charles Majoie, M.D.

  Radiology Department of Academic Medical Center Amsterdam

  PRINCIPAL INVESTIGATOR

• Yvo Roos, M.D.

  Neurology Department of Academic Medical Center Amsterdam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dean of the department of Neurosurgery

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 19, 2018
• Study Start: February 21, 2018
• Primary Completion: October 20, 2019
• Study Completion: October 26, 2019
• Last Updated: October 29, 2019

Record last verified: 2019-10

Locations

CN (1)