Clinical Trial Details
Randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion - A prospective, multicenter, randomized trial
The goal of this study is to make clear the efficacy of endovascular alone therapy for ischemic stroke.
Trial summarized by: Irene L Llorente, PhD Content reviewed by: Ralph Sacco, MD, MS
In a Japanese stroke population this trial did not show the noninferiority of direct EVT to bridging therapy with respect to favorable outcomes. However, intracerebral hemorrhages of direct EVT was significantly fewer than bridging therapy.
Purpose: To determine if endovascular therapy (EVT) is as effective as bridging therapy with EVT and intravenous thrombolysis (IVT) in acute ischemic stroke.?
Trial Design: prospective, multicenter, open-treatment trial. N= 204, mean age 74 years. Patients with ICA and M1 acute ischemic stroke were randomized within 4.5 hours of stroke symptom onset to either EVT alone or to IVT and EVT.
Primary Endpoints: Noninferiority: mRS of 0-2 90 days after onset of stroke.
|@90 Days||EVT||IVT + EVT||OR P value|
|mRS 0-2||59.4%||57.3%||OR 1.09 P=0.18
|Intracranial hemorrhage within 36 hours||33.7%||50.5%||)R 0.50 P=0.02|
|Mortality @ 90 days||7.9%||8.7%||P=1.00|
Results: Noninferiority of direct EVT to bridging therapy was not demonstrated.
This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities.
Rate of favorable outcome at 90 days between two groups was not significantly different. However, intracerebral hemorrhages of direct EVT was significantly fewer than bridging therapy. In a Japanese stroke population this trial did not show the noninferiority of direct EVT to bridging therapy with respect to favorable outcomes.
- Rate of Modified Rankin Scale (mRS) 0-2 at 90 days after onset: Unadjusted logistic regression model (ITT): odds ratio 1.09, 95% CI 0.63 - 1.90, p=0.17 for noninferiority.
- Shift analysis(ITT): odds ratio 0.97, 95% CI 0.60 - 1.56, p=0.27 for noninferiority.
- Unadjusted logistic regression model (PPT): odds ratio 1.06, 95% CI 0.60 - 1.88, p=0.22 for noninferiority
- Mortality at 90 days did not differ between the two groups (8 [7.9%] and 9 [8.7%], respectively; odds ratio 0.90, 95% CI 0.33-2.43, P=1.00
- Reperfusion rate at MT (TICI grade≥2B): odds ratio 0.89, 95% CI 0.51-1.55, p=0.78
- The rate of any intracranial hemorrhage within 36 hours from onset were 34 (33.7%) in the direct EVT group and 52 (50.5%) in the bridging therapy group (odds ratio, 0.50; 95% CI, 0.28 to 0.88; P=0.02).
- Symptomatic ICH (NINDS criteria) at 36h: odds ratio, 0.65; 95% CI, 0.25 to 1.67; P=0.48
- Symptomatic ICH (SIT-MOST criteria) at 36h: odds ratio, 0.75; 95% CI, 0.25 to 2.24; P=0.78
Recommended and supporting content:
- Presented by Kentaro Suzuki at International Stroke Conference 2020, Los Angeles, Calif.
- Kentaro Suzuki's presentation slides (PDF) from ISC 2020
- Kentaro Suzuki's Abstract from ISC 2020
- UMIN Registry: UMIN000021488(link opens in new window)
- Basic design: Parallel
- Randomization: Randomized
- Randomization unit: Cluster
- Blinding: Open (no one is blinded)
- Control: Active
- Inclusion criteria:
- Patients of from 18 to 85 years old
- Continued clinical symptoms in patients with acute cerebral infarction
- Pre mRS within 2
- Patients with ICA or M1 occlusion and be able to puncture within 4 hours.
- DWI-ASPECTS more than 5 or ASPECTS more than 6 at pre endovascular therapy
- NIHSS more than 6
- Puncture within 4 h from onset.
- Research consent have been obtained in writing from the person or alternative person
- Exclusion criteria:
- Contraindication of contrast agent or endovascular therapy
- Contraindication of IVT
- Presence of severe renal disorder (patients undergoing introduction of dialysis can be included)
- Pregnancy or possibility of pregnancy
- Unlikely to complete the study, such as due to progressive malignant tumor
- Judged as incompatible for the study by the investigators
Patients randomized to the direct EVT group receive EVT without IVT. EVT can be performed using several devices (e.g. Merci, Penumbra, Trevo, Solitaire, Revive, any stents and percutaneous angioplasty balloon). Patients randomized to the bridging therapy group receive IVT preceding EVT. Intravenous recombinant tissue plasminogen activator (rt-PA) is administered at 0.6 mg/kg body weight up to a maximum of 60 mg, 10% as bolus, and 90% as continuous infusion over 1 h according to the Japanese guidelines. EVT has to be initiated as soon as possible, within 90 min from hospital admission.
- Rate of Modified Rankin Scale (mRS) 0-2 at 90 days after onset.
- mRS score (Shift analysis)
- mRS score 0-2 (Per protocol analysis)
- Death at 90 days
- Reperfusion rate at MT (TICI grade≥2B)
- Rate of asymptomatic and symptomatic intracranial hemorrhage at 36 hours after onset.
Sponsors and Collaborators:
- Nippon Medical School
- Goyal, M, Menon, BK, van Zwam, WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387: 1723–1731.
- Broeg-Morvay, A, Mordasini, P, Bernasconi, C, et al. Direct mechanical intervention versus combined intravenous and mechanical intervention in large artery anterior circulation stroke: a matched-pairs analysis. Stroke 2016; 47: 1037–1044.
- Fischer, U, Kaesmacher, J, Mendes Pereira, V, et al. Direct mechanical thrombectomy versus combined intravenous and mechanical thrombectomy in large-artery anterior circulation stroke: a topical review. Stroke 2017; 48: 2912–2918.
- Weber, R, Nordmeyer, H, Hadisurya, J, et al. Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis. J Neurointerv Surg 2017; 9: 229–233.
- Presented by: Bruce C. Campbell, Ph.D., International Stroke Conference 2020, Los Angeles, CA
- Suzuki K, Kimura K, Takeuchi M, Morimoto M, Kanazawa R, Kamiya Y, Shigeta K, Ishii N, Takayama Y, Koguchi Y, Takigawa T, Hayakawa M, Ota T, Okubo S, Naito H, Akaji K, Kato N, Inoue M, Hirano T, Miki K, Ueda T, Iguchi Y, Fujimoto S, Otsuka T, Matsumaru Y. The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study). Int J Stroke. 2019 Oct;14(7):752-755.
- TRIAL REGISTRATION: UMIN000021488
Stroke, Ischemia, Cerebral Infarction, Cerebrovascular Disorders, Endovascular therapy, intravenous thrombolysis
Related Clinical Topics:
Fibrinolytic agents, Fibrin Modulating agents, Plasminogen, Tissue Plasminogen Activator
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