Basilar Artery Occlusion Chinese Endovascular Trial

Ischemic Stroke Clinical Trial

Official title:

Randomized Trial of Revascularization With Solitaire Stentriever Versus Best Medical Therapy in the Treatment of Acute Ischemic Stroke Due to Basilar Artery Occlusion Presenting Within 6-24 Hours of Symptom Onset

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02737189
• Other study ID #: Xuanwu201601
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 2016
• Est. completion date: June 2022

Study information

• Verified date: May 2022
• Source: Xuanwu Hospital, Beijing
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endovascular treatment of acute ischemic stroke has shown strong benefit in several prospective randomized trials in the anterior circulation and endovascular therapy for basilar artery occlusion has shown promising results in several single-arm studies. This has led to a broad adoption of these techniques which are now considered standard of care in many institutions despite the lack of adequate evidence to prove their benefit. Indeed, the rates of symptomatic intracerebral hemorrhage in these studies have consistently been around 5% which raises the question as to whether patients could actually be harmed as opposed to helped by these procedures. This is a prospective, multi-center, randomized, controlled, open, blinded-endpoint trial, with the aim to evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving better outcomes in subjects presenting with an acute ischemic stroke caused by occlusion of the basilar artery within 6-24 hours from symptom onset.

Description:

Study Objective: To evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving favourable outcomes defined as modified Rankin score (mRS) 0-3 at 90 days in subjects presenting with ischemic stroke due to basilar artery occlusion up to 24 hours from symptom onset.

Subject Population: Subjects presenting with acute ischemic stroke within 6-24 hours from symptom onset/last seen well and whose strokes are attributable to an occlusion of the basilar artery. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. The randomization employs a 1:1 ratio of mechanical embolectomy with Solitaire stentriever in conjunction with manual aspiration versus medical management alone. Randomization will be done under a stratification process using age, baseline National Institute of Health Stroke Scale (NIHSS) and therapeutic window. For the primary endpoint, subjects will be followed for 90 days post-randomization.Sample size is projected to be 318 patients.

Care providers: Vascular neurologists and trained interventional neuroradiologists or neurologists in certified comprehensive stroke centers that treat more than 500 acute stroke patients and perform more than 30 acute mechanical thrombectomies every year will treat patients. Neurointerventionalists have to have previously performed at least 10 thrombectomies with Solitaire device in acute ischemic stroke patients.

Interventions: Patients in both arms will be admitted at acute stroke units (or Intensive Care Unit if needed) and treated following the Chinese Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Concomitant medications and non-pharmacological therapies will be recorded. If a decision of stopping support life measures is adopted, this will be recorded in the Case Report Form (CRF).A maximum of six attempts to retrieve the thrombus in a single vessel can be made with any Solitaire device or aspiration. In case an atherosclerotic lesion is found underlying the occlusive lesion angioplasty/stenting through detachment of the Solitaire device will be allowed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 217
• Est. completion date: June 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Posterior circulation AIS within 6-24 hours from symptom onset/last seen well where patient is ineligible for i.v. thrombolytic treatment, or patient has received i.v. thrombolytic therapy without recanalization.

2. Occlusion (Thrombolysis in Myocardial Infarction, TIMI 0-1) of the basilar artery or intracranial segments of both vertebral arteries as evidenced by computed tomography (CT) angiography, magnetic resonance (MR) angiography or angiogram.

3. Age =18 and =80 years.

4. Baseline National Institutes of Health Stroke Scale (NIHSS) score obtained prior to randomization must be equal to or higher than 6 points.

5. No significant pre-stroke functional disability (modified Rankin Scale, mRS = 1).

6. Patient treatable within 24 hours from time last seen well. Isolated vertigo with nausea and/or vomiting is not considered onset of symptom.

7. Informed consent obtained from patient or acceptable patient surrogate.

Exclusion criteria

General Exclusion Criteria:

1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with international normalized ratio > 3.0.

2. Baseline platelet count < 50.000/µL.

3. Baseline blood glucose < 50mg/dL or > 400mg/dL.

4. Severe, sustained hypertension (systolic blood pressure > 220 mm Hg or diastolic blood pressure > 110 mm Hg).

5. Patients in sedation and/or intubated patients could not be included if baseline NIHSS is not obtained by a neurologist or emergency physician prior to sedation or intubation.

6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS.

7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.

8. History of life threatening allergy (more than rash) to contrast medium

9. Subjects who has received i.v. tissue plasminogen activator (t-PA) treatment beyond 4.5 hours from the beginning of the symptoms.

10. Patients with acute stroke within the first 48 hours after percutaneous cardiac, cerebrovascular interventions and major surgery (beyond 48h they should be randomized in BAOCHE or excluded for endovascular treatment if poor medical conditions).

11. Renal insufficiency with creatinine = 3 mg/dl.

12. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.

13. Subject participating in a study involving an investigational drug or device that would impact this study.

14. Cerebral vasculitis.

15. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations; mRS score at baseline must be = 1.

16. Unlikely to be available for 90 days follow-up.

Neuroimaging Exclusion Criteria:

1. Hypodensity amounting to a posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) < 6 and Pons-midbrain-index of = 3 on CT angiography source images or MR with diffusion-weighted imaging or NCCT.

2. CT or MR evidence of hemorrhage (the presence of microbleeds on MRI is allowed).

3. Complete cerebellar infarct on CT or MRI with significant mass effect and compression of the fourth ventricle.

4. Complete unilateral or bilateral thalamic infarction on CT or MRI

5. Evidence of vertebral occlusion, high grade stenosis or arterial dissection in the extracranial or intracranial segment that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment.

6. Subjects with occlusions in both anterior and posterior circulation.

7. Evidence of intracranial tumor (except small meningioma).

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Basilar Artery Occlusion
• Cerebrovascular Disorders
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Procedure:
• Mechanical embolectomy
Mechanical embolectomy with Solitaire stentriever in conjunction with manual aspiration

Drug:
• Medical Treatment
Best Medical Treatment and maximum supportive care, not including mechanical thrombectomy, no intra arterial treatment

Locations

Country	Name	City	State
China	Baotou Central Hospital	Baotou
China	Beijing Luhe Hospital	Beijing
China	Beijing Tiantan Hospital	Beijing
China	The Military General Hospital of Beijing, PLA	Beijing
China	Xuanwu Hospital	Beijing
China	The First People's Hospital of Changzhou	Changzhou
China	Chongqing Three Gorges Central Hospital	Chongqing
China	Xinqiao Hospital of Chongqing	Chongqing
China	Shengli Oilfield Hospital	Dongying
China	The Affiliated Hospital Of Guizhou Medical University	Guiyang
China	First Hospital of Jilin University	Jilin
China	Liaocheng Third People's Hospital	Liaocheng
China	Linyi People's Hospital	Linyi
China	Luoyang Central Hospital	Luoyang
China	Nanjing First People's Hospital	Nanjing
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing
China	Nanning Second People's Hospital	Nanning
China	Nantong University	Nantong
China	Nanyang Central Hospital	Nanyang
China	Changhai Hospital	Shanghai
China	Shenzhen Bao'an District People's Hospital	Shenzhen
China	Hebei General Hospital	Shijiazhuang
China	Second Affiliated Hospital of Soochow University	Suzhou
China	PLA 264 Hospital	Taiyuan
China	The First Affiliated Hospital of Shanxi Medical University	Taiyuan
China	Peking University Binhai Hospital	Tianjin
China	The Fifth Central Hospital of Tianjin	Tianjin
China	Tianjin Huanhu Hospital	Tianjin
China	Tianjin TEDA Hospital	Tianjin
China	The 101st Hospital of Chinese People's Liberation Army	Wuxi
China	The Affiliated Hospital of Northwest University, Xi'an NO.3 Hospital	Xi'an
China	Subei People's Hospital of Jiangsu Province	Yangzhou
China	Yantaishan Hospital	Yantai
China	Zhangzhou Municipal Hospital of Fujian Province	Zhangzhou
China	Henan Provincial Hospital	Zhengzhou
China	PLA 148 Hospital	Zibo

Sponsors (36)

Lead Sponsor

Collaborator

Xuanwu Hospital, Beijing

Affiliated Hospital of Nantong University, Baotou Central Hospital, Beijing Luhe Hospital, Beijing Tiantan Hospital, Changhai Hospital, Chongqing Three Gorges Central Hospital, Hebei General Hospital, Henan Provincial People's Hospital, Liaocheng People's Hospital, Linyi People's Hospital, Luoyang Central Hospital, Nanning Second People's Hospital, Nanyang Central Hospital, Peking University Binhai Hospital, PLA 148 Hospital, Zibo, Shandong, Second Affiliated Hospital of Soochow University, Shengli Oilfield Hospital, Shenzhen Bao'an District People's Hospital, Subei People's Hospital of Jiangsu Province, The 904 Hospital of PLA, The 985 Hospital of PLA, Taiyuan, Shanxi, The Affiliated Hospital Of Guizhou Medical University, The Affiliated Hospital of Northwest University, Xi'an NO.3 Hospital, The Fifth Central Hospital of Tianjin,TianJin, The First Affiliated Hospital of Dalian Medical University, The First Affiliated Hospital of Shanxi Medical University, The First Affiliated Hospital with Nanjing Medical University, The First Hospital of Jilin University, The First People's Hospital of Changzhou, The Military General Hospital of Beijing, PLA, Tianjin Huanhu Hospital, Tianjin TEDA Hospital, Xinqiao Hospital of Chongqing, Yantaishan Hospital, Zhangzhou Municipal Hospital of Fujian Province

Country where clinical trial is conducted

China, 

References & Publications (21)

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Hann S, Chalouhi N, Starke R, Gandhe A, Koltz M, Theofanis T, Jabbour P, Gonzalez LF, Rosenwasser R, Tjoumakaris S. Comparison of neurologic and radiographic outcomes with Solitaire versus Merci/Penumbra systems for acute stroke intervention. Biomed Res Int. 2013;2013:715170. doi: 10.1155/2013/715170. Epub 2013 Dec 30. — View Citation

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Lindsberg PJ, Pekkola J, Strbian D, Sairanen T, Mattle HP, Schroth G. Time window for recanalization in basilar artery occlusion: Speculative synthesis. Neurology. 2015 Nov 17;85(20):1806-15. doi: 10.1212/WNL.0000000000002129. Review. — View Citation

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Liu X, Dai Q, Ye R, Zi W, Liu Y, Wang H, Zhu W, Ma M, Yin Q, Li M, Fan X, Sun W, Han Y, Lv Q, Liu R, Yang D, Shi Z, Zheng D, Deng X, Wan Y, Wang Z, Geng Y, Chen X, Zhou Z, Liao G, Jin P, Liu Y, Liu X, Zhang M, Zhou F, Shi H, Zhang Y, Guo F, Yin C, Niu G, Zhang M, Cai X, Zhu Q, Chen Z, Liang Y, Li B, Lin M, Wang W, Xu H, Fu X, Liu W, Tian X, Gong Z, Shi H, Wang C, Lv P, Tao Z, Zhu L, Yang S, Hu W, Jiang P, Liebeskind DS, Pereira VM, Leung T, Yan B, Davis S, Xu G, Nogueira RG; BEST Trial Investigators. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol. 2020 Feb;19(2):115-122. doi: 10.1016/S1474-4422(19)30395-3. Epub 2019 Dec 9. — View Citation

Macleod MR, Davis SM, Mitchell PJ, Gerraty RP, Fitt G, Hankey GJ, Stewart-Wynne EG, Rosen D, McNeil JJ, Bladin CF, Chambers BR, Herkes GK, Young D, Donnan GA. Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke. Cerebrovasc Dis. 2005;20(1):12-7. Epub 2005 May 30. — View Citation

Palaniswami M, Yan B. Mechanical Thrombectomy Is Now the Gold Standard for Acute Ischemic Stroke: Implications for Routine Clinical Practice. Interv Neurol. 2015 Oct;4(1-2):18-29. doi: 10.1159/000438774. Epub 2015 Sep 18. Review. — View Citation

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Writing Group for the BASILAR Group, Zi W, Qiu Z, Wu D, Li F, Liu H, Liu W, Huang W, Shi Z, Bai Y, Liu Z, Wang L, Yang S, Pu J, Wen C, Wang S, Zhu Q, Chen W, Yin C, Lin M, Qi L, Zhong Y, Wang Z, Wu W, Chen H, Yao X, Xiong F, Zeng G, Zhou Z, Wu Z, Wan Y, Peng H, Li B, Hu X, Wen H, Zhong W, Wang L, Jin P, Guo F, Han J, Fu X, Ai Z, Tian X, Feng X, Sun B, Huang Z, Li W, Zhou P, Tu M, Sun X, Li H, He W, Qiu T, Yuan Z, Yue C, Yang J, Luo W, Gong Z, Shuai J, Nogueira RG, Yang Q. Assessment of Endovascular Treatment for Acute Basilar Artery Occlusion via a Nationwide Prospective Registry. JAMA Neurol. 2020 May 1;77(5):561-573. doi: 10.1001/jamaneurol.2020.0156. — View Citation

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Yeung JT, Matouk CC, Bulsara KR, Sheth KN. Endovascular revascularization for basilar artery occlusion. Interv Neurol. 2015 Jan;3(1):31-40. doi: 10.1159/000368968. Review. — View Citation

Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, Li Y, Wang L, Liu Y, Yin P, Liu J, Yu S, Tan F, Barber RM, Coates MM, Dicker D, Fraser M, González-Medina D, Hamavid H, Hao Y, Hu G, Jiang G, Kan H, Lopez AD, Phillips MR, She J, Vos T, Wan X, Xu G, Yan LL, Yu C, Zhao Y, Zheng Y, Zou X, Naghavi M, Wang Y, Murray CJ, Yang G, Liang X. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016 Jan 16;387(10015):251-72. doi: 10.1016/S0140-6736(15)00551-6. Epub 2015 Oct 26. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of patients achieving favourable outcomes defined as mRS 0-3 at 90 days	The primary objective of this study is to evaluate the hypothesis that mechanical embolectomy with the Solitaire device is superior to medical management alone in achieving favourable outcomes (mRS = 3) at 90 days in subjects presenting with an acute ischemic stroke caused by occlusion of the basilar artery within 6-24 hours from symptom onset.	90 days
Secondary	Dramatic early favorable response	Dramatic early favorable response as determined by an National Institute of Health stroke scale (NIHSS) of 0-2 or NIHSS improvement = 8 points at 24 (-2/+12) hours.	24 (-2/+12) hours
Secondary	Dichotomized mRS score (0-2 versus 3-6 and 0-4 versus 5-6 )		90 days
Secondary	Proportion of patients achieving meaningful outcomes defined as mRS 0-4 at 12 months.		12 months
Secondary	Final infarct volume and the change of infarct volume compared with baseline	Infarct volume evaluated on Computed Tomography (CT) or Magnetic Resonance (MR) at 24 hours (-2/+12 hours)	24 hours (-2/+12 hours)
Secondary	Vessel recanalization with Arterial Occlusive Lesion (AOL) grades	Vessel recanalization at 24 hours (-2/+12 hours) in both treatment groups assessed by using Arterial Occlusive Lesion (AOL) grades	24 hours (-2/+12 hours)
Secondary	Modified Rankin Score (mRS)		90 days
Secondary	Barthel Index		90 days
Secondary	NIHSS		90 days
Secondary	Quality of life analysis	Quality of life analysis as measured by EuroQol/EQ5D and SF-36 at 3 month, 6 months and 1 year, between interventional therapy vs medical therapy alone	3 month, 6 months and 1 year
Secondary	Mortality		at 90 days
Secondary	Symptomatic intracranial hemorrhage (SICH)		24 (-2/+12) hours
Secondary	Serious Adverse Events		1 year
Secondary	Montreal Cognition Test (MOCA)		90 days
Secondary	Immediate Post-Endovascular Treatment Recanalization (for the Solitaire arm only)	Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 in the post-procedure angiography.	Immediate Post-Endovascular Treatment
Secondary	Procedural related complications	arterial perforation, arterial dissection, embolization in a previously uninvolved vascular territory and so on.	Perioperative period