Clinical trial NCT02441556: Acute Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment
Official title: Acute Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke Due to Basilar Artery Occlusion
Acute Cerebrovascular Accidents
Keywords: thrombectomy
rt-PA
stroke
endovascular treatment
randomized
Lead sponsor: Jinling Hospital, China
Sponsor class: OTHER
First posted: 2015-05-12
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion within 8 hours of estimated occlusion time.

Detailed description: This clinical trial is designed to compare the safety and efficacy of endovascular treatment plus standard medical therapy with standard medical therapy alone for acute BA occlusion presented within 8 h of estimated occlusion time. There is only one ongoing clinical trial-Basilar Artery International Cooperation Study (BASICS) (NCT01717755) aimed to evaluate the efficacy and safety of additional intra-arterial treatment after intravenous treatment in 750 patients with BA occlusion, which was anticipated to be completed in Oct 2017. Initiation of intra-arterial therapy should be feasible within 6 hours of estimated time of BA occlusion. And patients are required to have an NIHSS ≥ 10 at time of randomization, and take IV rt-PA, age between 18-85 years old.

In this trial, the investigators did not have age or NIHSS score limit, patients who did not fulfill the requirements for IV rt-PA can also be included into the trial, the investigators also extended the time window to 8 hours which will accelerate the recruitment of potential subjects. In endovascular treatment arm, the time interval between randomization to procedure finish will be controlled within 120 mins. The preparation of endovascular treatment will start immediately after randomization for those eligible patients for IV rt-PA within 4.5 hours after acute stroke onset, with no need to wait for the one-hour rt-PA infusion. A positive trial will suggest substantial clinical benefit from endovascular treatment plus standard medical therapy over standard medical therapy. This trial may provide novel evidence of adopting endovascular treatment for acute patients with BA occlusion, which may consequently advance our current approach for acute stroke treatment.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years;
2. Acute ischemic stroke consistent with infarction in the basilar artery territory;
3. Basilar artery occlusion confirmed by CTA/MRA/DSA, within 8 hours of estimated occlusion time;
4. Written informed consent from patient or surrogate, if unable to provide consent.

Exclusion Criteria:

1. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of Cerebral hemorrhage on presentation;
2. Premorbid mRS ≥ 3 points;
3. Currently in pregnant or lactating;
4. Known serious sensitivity to radiographic contrast agents and nitinol metal;
5. Current participation in another investigation drug or device study;
6. Uncontrolled hypertension defined as systolic blood pressure \> 185 mmHg or diastolic blood pressure \> 110 mmHg that cannot be controlled except with continuous parenteral antihypertensive medication;
7. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with INR \>1.7 or institutionally equivalent prothrombin time;
8. Baseline lab values: glucose \< 50 mg/dl or \> 400 mg/dl, platelets \<100\*109/L, or Hct\<25%;
9. Arterial tortuosity that would prevent the device from reaching the target vessel;
10. Life expectancy less than 1 year;
11. History of major hemorrhage in the past 6 months;
12. Angiographic evidence of significant cerebellar mass effect or acute hydrocephalus.
13. Angiographic evidence of bilateral extended brainstem ischemia.

Primary outcomes:
measure: modified Rankin Scale (mRS)
timeFrame: at 90 days from randomization
Secondary outcomes:
measure: mRS score 0-2
timeFrame: at 90 days from randomization
measure: Change of mRS score(shift analysis)
timeFrame: at 90 days from randomization
measure: Vessel recanalization rate evaluated by CT angiography or MRA
timeFrame: at 24 hours from randomization
measure: PC-ASPECT score on CT/MRI
timeFrame: at 24 hours from randomization
measure: GCS score
timeFrame: at 24 hours from randomization
measure: NIHSS score
timeFrame: at 24 hours from randomization
measure: GCS score
timeFrame: at 5-7 days from randomization
measure: NIHSS score
timeFrame: at 5-7 days from randomization
measure: EuroQol 5D (EQ-5D)
timeFrame: at 90 days from randomization
measure: mortality
timeFrame: at 3 months from randomization
measure: symptomatic intracerebral hemorrhage (ICH)
timeFrame: within 24 hours from randomization
measure: incidence of non-intracerebral hemorrhage complications
timeFrame: at 90 days from randomization
measure: severity of non-intracerebral hemorrhage complications
timeFrame: within 90 days from randomization
measure: incidence of nonbleeding severe adverse events (SAEs)
timeFrame: within 90 days from randomization
measure: severity of nonbleeding severe adverse events (SAEs)
timeFrame: within 90 days from randomization
measure: incidence of procedure and device related complications
timeFrame: within 90 days from randomization
measure: severity of procedure and device related complications
timeFrame: within 90 days from randomization
Other outcomes:
Locations:
city: Bengbu
country: China
facility: 123rd Hospital of The People's Liberation Army
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: the First Affiliated Hospital of An'hui Medical University
state: Anhui
city: Huainan
country: China
facility: the First People's Hospital of Huainan
state: Anhui
city: Lu'an
country: China
facility: Lu'an Affiliated Hospital of Anhui Medical University
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Chongqing
country: China
facility: Daping Hospital, Third Military Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Military Region
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
city: Xiamen
country: China
facility: 175th hospital of PLA, the Affiliated Southeast Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Affiliated Zhongshan Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong No.2 Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Chinese Armed Police Force Guangdong Armed Police Corps hospital
state: Guangdong
city: Maoming
country: China
facility: Maoming People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Nanshan Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital,Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Zhongshan Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan No.1 Hospital
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Nanjing
country: China
facility: Jinling Hospital, Medical School of Nanjing University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First Hospital, Nanjing Medical University
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Wuxi
country: China
facility: 101st hospital of PLA
state: Jiangsu
city: Xuzhou
country: China
facility: the Second Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Yancheng
country: China
facility: the Third People's Hospital of Yancheng
state: Jiangsu
city: Yangzhou
country: China
facility: Yangzhou No.1 People's Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: the First People's Hospital of Yangzhou， Yangzhou University
state: Jiangsu
city: Yangzhou
country: China
facility: Yangzhou Hongquan Hospital
state: Jiangsu
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Taian
country: China
facility: Taian City Central Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Chengdu
country: China
facility: Chengdu Military General Hospital
state: Sichuan
city: Chengdu
country: China
facility: Sichuan People's Hospital
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Hangzhou
country: China
facility: the First People's Hospital of Hangzhou,Nanjing Medical University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Lishui
country: China
facility: Lishui Central Hospital
state: Zhejiang
city: Chongqing
country: China
facility: Xinqiao Hospital, the Third Military Medical University
Study officials:
affiliation: Departmnet of Neurology, Jinling Hospital
name: Xinfeng Liu, Doctor
role: STUDY_CHAIR
References:
citation: Schonewille WJ, Wijman CA, Michel P, Rueckert CM, Weimar C, Mattle HP, Engelter ST, Tanne D, Muir KW, Molina CA, Thijs V, Audebert H, Pfefferkorn T, Szabo K, Lindsberg PJ, de Freitas G, Kappelle LJ, Algra A; BASICS study group. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol. 2009 Aug;8(8):724-30. doi: 10.1016/S1474-4422(09)70173-5. Epub 2009 Jul 3.
citation: National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
citation: Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
citation: Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, Akhtar N, Orouk FO, Salam A, Shuaib A, Alexandrov AV; CLOTBUST Investigators. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007 Mar;38(3):948-54. doi: 10.1161/01.STR.0000257304.21967.ba. Epub 2007 Feb 8.
citation: Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013 Mar 7;368(10):904-13. doi: 10.1056/NEJMoa1213701. Epub 2013 Feb 6.
citation: Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7;368(10):893-903. doi: 10.1056/NEJMoa1214300. Epub 2013 Feb 7.
citation: Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013 Mar 7;368(10):914-23. doi: 10.1056/NEJMoa1212793. Epub 2013 Feb 8.
citation: Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP; Multi MERCI Investigators; Frei D, Grobelny T, Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008 Apr;39(4):1205-12. doi: 10.1161/STROKEAHA.107.497115. Epub 2008 Feb 28.
citation: Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, Liebeskind DS, Smith WS; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6;380(9849):1231-40. doi: 10.1016/S0140-6736(12)61299-9. Epub 2012 Aug 26.
citation: Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO; SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012 Oct 6;380(9849):1241-9. doi: 10.1016/S0140-6736(12)61384-1. Epub 2012 Aug 26.
citation: Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.
citation: Mattle HP, Arnold M, Lindsberg PJ, Schonewille WJ, Schroth G. Basilar artery occlusion. Lancet Neurol. 2011 Nov;10(11):1002-14. doi: 10.1016/S1474-4422(11)70229-0.
citation: Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013 Mar;44(3):870-947. doi: 10.1161/STR.0b013e318284056a. Epub 2013 Jan 31.
citation: 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.
citation: Liu X, Xu G, Liu Y, Zhu W, Ma M, Xiong Y, Zi W, Dai Q, Leung T, Yan B, Davis S, Liebeskind DS, Pereira VM, Nogueira RG; BEST Trial Investigators. Acute basilar artery occlusion: Endovascular Interventions versus Standard Medical Treatment (BEST) Trial-Design and protocol for a randomized, controlled, multicenter study. Int J Stroke. 2017 Oct;12(7):779-785. doi: 10.1177/1747493017701153. Epub 2017 Mar 31.