Direct Endovascular Treatment Versus Bridging Treatment In Basilar Artery Occlusive Stroke
- Conditions
- Acute Ischemic StrokeAlteplaseEndovascular TreatmentBasilar Artery OcclusionThrombosis
- Interventions
- Procedure: Endovascular treatmentDrug: Intravenous thrombolysis (Alteplase)
- Registration Number
- NCT05631847
- Lead Sponsor
- Sichuan Academy of Medical Sciences
- Brief Summary
Currently, both intravenous thrombolysis (IVT) followed by endovascular treatment (EVT) and EVT alone are widely used for the treatment of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) (AIS-BAO), but no direct comparison of their efficacy and safety was reported. Only a limited number of cohort and registry studies have preliminarily compared the two strategies in the treatment of AIS-BAO, with results generally indicating that IVT followed by EVT was slightly superior to EVT alone. However, these findings are generally limited by small sample sizes, heterogeneous inclusion and exclusion criteria, different endpoint definitions, and distinct study designs, leading to inconsistent conclusions. Therefore, this study plans to conduct a multicentre, prospective, open-label, blinded endpoint evaluation, randomized controlled trial comparing the efficacy and safety of IVT followed by EVT and EVT alone in the treatment of patients with AIS-BAO who are eligible for both treatment strategies within 4.5 hours of symptom onset. This study intends to include patients with AIS due to BAO fulfilling the following inclusion criteria: patients with AIS caused by BAO confirmed by CTA/MRA/DSA; IVT can be started within 4.5 hours after symptoms onset; Age ≥ 18 years old; NIHSS score ≥ 6.
The primary endpoint of the study is the proportion of patients achieving mRS ≤ 2 at 90±14 days after stroke onset.
- Detailed Description
Stroke is a leading cause of death and disability in China, with acute ischemic stroke (AIS) accounting for approximately 85% of all acute strokes. Among these, large vessel occlusion-related AIS (AIS-LVO) represents about 20% of cases. Posterior circulation infarction, which occur in the vertebrobasilar artery territory, comprise 20-25% of all ischemic strokes. Although less common than anterior circulation ischemic strokes, posterior circulation infarctions-particularly AIS caused by basilar artery occlusion (AIS-BAO)-often present with severe symptoms and poor outcomes. Due to the heterogeneity of initial symptoms and diagnostic challenges, AIS-BAO frequently results in poor prognoses, posing significant challenges in clinical diagnosis and treatment.
The safety and efficacy of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset in AIS have been confirmed by numerous randomized controlled trials (RCTs). However, the heterogeneous presentation of posterior circulation AIS, the difficulty in clinical recognition compared to anterior circulation AIS, and the severe neurological deficits-especially the high mortality rate of AIS-BAO-pose various limitations on IVT. Endovascular treatment (EVT), including thrombectomy techniques, has substantially reduced the mortality and disability rates of patients with AIS-LVO. The key to treating AIS-BAO is recanalizing the acutely occluded basilar artery and rescuing the ischemic penumbra. Large RCTs have demonstrated that early EVT achieves better clinical outcomes in anterior circulation AIS-LVO patients eligible for mechanical thrombectomy compared to IVT alone.
In recent years, while multiple large RCTs have confirmed the efficacy of EVT for anterior circulation AIS-LVO, evidence for EVT in posterior circulation AIS-LVO remains limited. The BEST trial enrolled AIS patients with vertebrobasilar artery occlusion within 8 hours of symptom onset to compare EVT plus standard medical treatment versus medical treatment alone. The results showed that the combination group achieved better outcomes at 90 days, with no significant difference in mortality or symptomatic intracranial hemorrhage (sICH) rates compared to the medical treatment-only group. Similarly, the BASICS trial, an international multicenter RCT, enrolled 300 AIS-BAO patients within 6 hours of symptom onset and compared EVT combined with standard medical treatment to standard medical treatment alone. This study found no significant differences between the two groups in good functional outcomes, sICH, or mortality.
Recently, two studies focusing on thrombectomy for AIS-BAO reported promising results. The BAOCHE study randomized AIS-BAO patients who presented 6-24 hours after symptom onset into a thrombectomy plus standard medical treatment group or a standard medical treatment-only group. The primary endpoint was the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 at 90 days. A total of 217 patients (110 in the combination group, 107 in the medical treatment group) were enrolled, and the results demonstrated that thrombectomy performed within 6-24 hours led to better functional outcomes at 90 days. The ATTENTION study, another RCT conducted across 36 stroke centers in China, enrolled AIS-BAO patients within 12 hours of symptom onset. Patients were randomized 2:1 to thrombectomy plus optimal medical treatment or optimal medical treatment alone. The primary outcome was the proportion of patients achieving an mRS score of 0-3 at 90 days, and 340 patients (226 in the combination group, 114 in the medical treatment group) were enrolled. The results showed that thrombectomy within 12 hours significantly improved functional outcomes. Both studies demonstrated that thrombectomy combined with medical treatment yielded better outcomes than medical treatment alone for AIS-BAO. However, questions remain regarding the optimal timing, treatment modalities, bridging strategies, and anesthesia options for EVT in posterior circulation AIS. Further exploration is required to rapidly identify posterior circulation strokes and select appropriate EVT strategies based on clinical indications.
Clinically, the morbidity and mortality of posterior circulation AIS-LVO exceed 80%. AIS-BAO, in particular, is a neurological emergency with extremely high mortality if untreated, significantly affecting patients' quality of life and imposing substantial medical and financial burdens on families and society. IVT remains the most effective ultra-early treatment for AIS within 6 hours of onset. However, the adoption of IVT for posterior circulation AIS is lower than that for anterior circulation AIS, potentially due to delays in diagnosis or missed diagnoses caused by the heterogeneity of AIS-BAO symptoms. Among AIS patients receiving IVT, posterior circulation strokes (PCS) account for about 5-19%. Studies comparing the efficacy and safety of IVT in PCS and anterior circulation strokes (ACS) have found that while the risk of hemorrhagic complications is halved for PCS, functional outcomes are similar, but mortality is higher. Clinically, IVT can be used as standalone therapy for AIS-BAO or as a prelude to EVT. Which approach better improves AIS-BAO outcomes remains uncertain.
To date, most studies on IVT with EVT have focused on anterior circulation AIS. Both IVT and EVT are time-dependent treatments for AIS, with EVT success hinging on prompt initiation and optimization of processes to reduce door-to-puncture time (DTP). The SKIP trial found no significant difference in the time from randomization to femoral artery puncture between only EVT and IVT with EVT. Similarly, the DEVT trial, conducted in China, also reported no difference in this time interval between the two groups. A meta-analysis of 38 observational studies including 11,798 AIS-LVO patients (56% of whom underwent IVT with EVT) also confirmed no significant difference in EVT procedural time between the two groups. For anterior circulation AIS-LVO, four recent RCTs showed mixed results. DIRECT-MT and DEVT demonstrated that only EVT was non-inferior to IVT with EVT in terms of good functional outcomes at 90 days, while SKIP and MR CLEAN-IV did not confirm non-inferiority. Thus, EVT alone requires further robust evidence\[17, 18\]. Regarding safety, all four RCTs confirmed that IVT with EVT does not increase sICH rates. Additionally, the aforementioned meta-analysis\[16\] confirmed that IVT with EVT does not increase sICH risk. SKIP, DIRECT-MT, and DEVT further showed no significant difference in mortality between the two groups. However, the meta-analysis suggested that IVT with EVT significantly reduces 90-day mortality compared to only EVT. A real-world study also found that IVT with EVT was independently associated with lower 90-day mortality compared to only EVT.
Does IVT before EVT achieve higher recanalization rates? A retrospective study including 93 AIS patients with middle cerebral artery occlusion showed that IVT with EVT resulted in a higher proportion of reperfusion within 1 hour of femoral artery puncture compared to only EVT. Moreover, IVT with EVT achieved significantly higher rates of successful reperfusion (mTICI ≥ 2b). The DIRECT-MT study found that IVT with EVT caused fewer new infarctions from thrombus fragmentation than only EVT. Similarly, post-hoc analyses of the ESCAPE trial demonstrated that IVT with EVT significantly reduced new infarct risk compared to only EVT. Another study of 57 patients with M1 segment occlusions reported that IVT with EVT often required fewer thrombectomy passes to achieve recanalization compared to only EVT.
Combination therapy combines the rapidity of IVT with the high recanalization rates of EVT, theoretically offering better outcomes than only EVT. However, most of these studies focus on anterior circulation stroke treatment. To date, no large-scale RCTs have specifically evaluated EVT with or without prior IVT for AIS-BAO. Therefore, we plan to conduct a multicenter, prospective, randomized controlled study to assess the impact of different EVT strategies on outcomes in AIS-BAO.
The primary objective of this trial is to compare the efficacy and safety of IVT followed by EVT versus EVT alone in patients with AIS caused by BAO who are eligible for both treatment strategies within 4.5 hours after symptom onset.
The secondary objectives include assessing the effects of the two treatment strategies on neurological function (assessed by National Institutes of Health Stroke Scale \[NIHSS\] score), activities of daily living (assessed by Barthel Index \[BI\] score), quality of life (assessed by EQ-5D-5L score), cerebrovascular reperfusion (assessed by eTICI), cerebrovascular recanalization (assessed by mAOL), infarct size (assessed by PC-ASPECTS and quantitative imaging detection), mortality, and the incidence of symptomatic intracranial hemorrhage (sICH).
This is a multicentre, prospective, open-label, blinded endpoint evaluation, randomized controlled clinical trial (PROBE design). Based on published observational studies, this trial will first validate the superiority of IVT followed by EVT compared with EVT alone. However, given the limited prior evidence and the current findings from anterior circulation stroke studies, this trial will also validate the non-inferiority of EVT compared with IVT followed by EVT alone if the efficacy of the two treatment strategies is found to be comparable.
An interim analysis is scheduled after one-third of the sample size completes follow-up for the primary endpoint. The primary purpose of the interim analysis is to allow for sample size re-estimation. The data and safety monitoring board (DSMB) will calculate the conditional power based on the current data and provide recommendations to the BEST-BAO research team regarding potential sample size adjustments.
The trial will be conducted at nationally recognized stroke centers and is expected to last for 3 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 340
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Direct endovascular treatment group Endovascular treatment Direct endovascular treatment (EVT) without intravenous thrombolysis (IVT) Bridging treatment group Endovascular treatment Intravenous thrombolysis (IVT) followed by endovascular treatment (EVT) Bridging treatment group Intravenous thrombolysis (Alteplase) Intravenous thrombolysis (IVT) followed by endovascular treatment (EVT)
- Primary Outcome Measures
Name Time Method Proportion of patients achieving mRS ≤ 2. At 90±14 days after stroke onset. The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability.
- Secondary Outcome Measures
Name Time Method Proportions of patients with mRS = 0 or 1. At 90±14 days after stroke onset. The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability.
Proportions of patients with mRS = 0-3. At 90±14 days after stroke onset The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability.
The mRS score. At 90±14 days after stroke onset The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability.
NIHSS (the National Institutes of Health Stroke Scale) score At 18-24 hours after procedure, 24-74 hours after procedure, and 5-7 days after stroke onset and their changes from baseline. The NIHSS score is an ordinal hierarchical scale to evaluate the symptomatic severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores suggesting a more severe deficit.
Proportions of patients with a NIHSS score = 0 or 1, a NIHSS score = 0-2, a NIHSS score improvement ≥ 4 points, and a NIHSS score improvement ≥ 8 points. At 18-24 hours after procedure, 24-74 hours after procedure, and 5-7 days after stroke onset. The NIHSS score is an ordinal hierarchical scale to evaluate the symptomatic severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores suggesting a more severe deficit.
Glasgow Coma Scale At 18-24 hours after procedure, 24-74 hours after procedure, and 5-7 days after stroke onset and their changes from baseline. The Glasgow Coma Scale (GCS) is widely used to assess the level of consciousness in stroke patients, postoperative patients with brain injuries, and those with varying degrees of coma due to other causes.
BI score and the proportion with BI = 95-100. At 30±7 and 90±14 days after stroke onset The Barthel Index (BI) is an ordinal scale used to measure performance in 10 activities of daily living. Scores range from 0 to 100, with higher scores indicating better performance in these activities.
EQ-5D-5L (the European Quality of Life 5-Dimension 5-Level) score At 90±14 days after after stroke onset. The EQ-5D-5L score is an ordinal hierarchical scale to evaluate the quality of life. Scores range from -0.39 to 1, with higher scores indicating a better quality of life.
eTICI (Extended Treatment In Cerebral Ischemia) score and successful reperfusion rates. Before and after EVT. The eTICI is an ordinal hierarchical scale ranging from 0 to 3, with higher scores suggesting better antegrade reperfusion of the previously occluded target artery ischemic territory.
mAOL score and recanalization rates At 24-72 hours after procedure. The modified Arterial Occlusive Lesion (mAOL) scale is a standardized method used to evaluate arterial recanalization in acute ischemic stroke patients following endovascular treatment. It assesses the degree of reopening in the previously occluded artery, providing critical insights into the success of the intervention.
PC-ASPECTS score At 24-72 hours after procedure and 5-7 days after stroke onset. The Posterior Circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) is a standardized tool used to evaluate early ischemic changes in the posterior circulation territory.
Lesion volume. At 24-72 hours after procedure and 5-7 days after stroke onset. Quantitative imaging detection.
All-cause mortality Within 7, 30±7, and 90±14 days after stroke onset. The proportion of total deaths caused by various reasons in both arms
Proportions of patients with intracranial hemorrhage and symptomatic intracranial hemorrhage At 24-72 hours after procedure and 5-7 days after stroke onset. The 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.
New regional cerebral embolisms. During EVT. Embolization to new territory assessment.Type A: Catheter was manipulated past the ostium of the new territory (e.g. large ACA infarct in a patient with an initial M1 occlusion): greater likelihood that infarct is related to the procedure.
Type B: Catheter was not manipulated past the ostium of the new territory (e.g. left PICA infarct in a patient with an initial right M1 occlusion): lower likelihood that infarct is related to procedure.Proportions of patients with new cerebral infarction At 24-72 hours after procedure and 5-7 days after stroke onset. The proportion of the new cerebral infarction compared with the onset of symptoms evaluated with magnetic resource imaging test
EVT procedure-related complications. Within 90±14 days after stroke onset. The pseudoaneurysm and hematoma at puncture site caused by various reasons is one of the important indicators reflecting puncture complications.
Trial Locations
- Locations (85)
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
🇨🇳Hefei, Anhui, China
Banan Hospital Affiliated to Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Chongqing Sanbo Chang'an Hospital
🇨🇳Chongqing, Chongqing, China
Chongqing University Affiliated S Central Hospital
🇨🇳Chongqing, Chongqing, China
Chongqing University Medical University Affiliated Yongchuan Hospital
🇨🇳Chongqing, Chongqing, China
Hechuan District People's Hospital
🇨🇳Chongqing, Chongqing, China
Liangping District People's Hospital
🇨🇳Chongqing, Chongqing, China
The First People's Hospital of Liangjiang New Area
🇨🇳Chongqing, Chongqing, China
Yubei District People's Hospital
🇨🇳Chongqing, Chongqing, China
Zhangzhou Hospital
🇨🇳Zhangzhou, Fujian, China
The Fifth People's Hospital Affiliated to Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Maoming County Traditional Chinese Medicine Hospital
🇨🇳Maoming, Guangdong, China
Yuebei People's Hospital
🇨🇳Shaoguan, Guangdong, China
Yulin First People's Hospital
🇨🇳Yulin, Guangxi, China
Qiandongnan Miao and Dong Autonomous Prefecture People's Hospital
🇨🇳Kaili, Guizhou, China
Tongren People's Hospital
🇨🇳Tongren, Guizhou, China
Qianxinan Buyei and Miao Autonomous Prefecture People's Hospital
🇨🇳Xingyi, Guizhou, China
Anyang People's Hospital
🇨🇳Anyang, Henan, China
Jiaozuo Second People's Hospital
🇨🇳Jiaozuo, Henan, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
Zhoukou Central Hospital
🇨🇳Zhoukou, Henan, China
Zhumadian Central Hospital
🇨🇳Zhumadian, Henan, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
Changde First People's Hospital
🇨🇳Changde, Hunan, China
Zhuzhou Central Hospital
🇨🇳Zhuzhou, Hunan, China
Jingjiang People's Hospital
🇨🇳Jingjiang, Jiangsu, China
The First People's Hospital of Suqian City
🇨🇳Suqian, Jiangsu, China
Yancheng First People's Hospital
🇨🇳Yancheng, Jiangsu, China
Jilin University Sino Japanese Friendship Hospital
🇨🇳Changchun, Jilin, China
The First Hospital of Jilin University
🇨🇳Jilin, Jilin, China
Tieling Central Hospital
🇨🇳Tieling, Liaoning, China
Yingkou Central Hospital
🇨🇳Yingkou, Liaoning, China
Heze Municipal Hospital
🇨🇳Heze, Shandong, China
Linyi Traditional Chinese Medicine Hospital
🇨🇳Linyi, Shandong, China
Rizhao Traditional Chinese Medicine Hospital
🇨🇳Rizhao, Shandong, China
The Second Affiliated Hospital of Shandong First Medical University
🇨🇳Taian, Shandong, China
Bazhong Central Hospital
🇨🇳Bazhong, Sichuan, China
Chengdu Third People's Hospital
🇨🇳Chengde, Sichuan, China
Sichuan Third People's Hospital
🇨🇳Chengdu, Sichuan, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Affiliated Hospital of Chengdu Medical College
🇨🇳Chengdu, Sichuan, China
Chengdu Fifth People's Hospital
🇨🇳Chengdu, Sichuan, China
Chengdu First People's Hospital
🇨🇳Chengdu, Sichuan, China
Chengdu Second People's Hospital
🇨🇳Chengdu, Sichuan, China
Chongzhou People's Hospital
🇨🇳Chengdu, Sichuan, China
Dayi County People's Hospital
🇨🇳Chengdu, Sichuan, China
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
🇨🇳Chengdu, Sichuan, China
Western Theater General Hospital
🇨🇳Chengdu, Sichuan, China
Deyang People's Hospital
🇨🇳Deyang, Sichuan, China
Guang'an Central Hospital
🇨🇳Guang'an, Sichuan, China
Guanghan People's Hospital
🇨🇳Guanghan, Sichuan, China
Guangyuan Central Hospital
🇨🇳Guangyuan, Sichuan, China
Guangyuan First People's Hospital
🇨🇳Guangyuan, Sichuan, China
Jintang County People's Hospital
🇨🇳Jintang, Sichuan, China
Leshan People's Hospital
🇨🇳Leshan, Sichuan, China
Affiliated Hospital of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Meishan Second People's Hospital
🇨🇳Meishan, Sichuan, China
Meishan Traditional Chinese Medicine Hospital
🇨🇳Meishan, Sichuan, China
Mianyang 404 Hospital
🇨🇳Mianyang, Sichuan, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
Mianyang Third People's Hospital
🇨🇳Mianyang, Sichuan, China
Affiliated Hospital of North Sichuan Medical College
🇨🇳Nanchong, Sichuan, China
Langzhong People's Hospital
🇨🇳Nanchong, Sichuan, China
Nanchong Central Hospital
🇨🇳Nanchong, Sichuan, China
Yilong County People's Hospital
🇨🇳Nanchong, Sichuan, China
Neijiang Second People's Hospital
🇨🇳Neijiang, Sichuan, China
Pangang Group General Hospital
🇨🇳Panzhihua, Sichuan, China
Panzhihua Central Hospital
🇨🇳Panzhihua, Sichuan, China
Pingchang County People's Hospital
🇨🇳Pingchang, Sichuan, China
Shifang People's Hospital
🇨🇳Shifang, Sichuan, China
Suining Central Hospital
🇨🇳Suining, Sichuan, China
Suining First People's Hospital
🇨🇳Suining, Sichuan, China
The First People's Hospital of Liangshan Yi Autonomous Prefecture
🇨🇳Xichang, Sichuan, China
Ya'an People's Hospital
🇨🇳Ya'an, Sichuan, China
Yibin First People's Hospital
🇨🇳Yibin, Sichuan, China
Yibin Second People's Hospital
🇨🇳Yibin, Sichuan, China
Zigong First People's Hospital
🇨🇳Zigong, Sichuan, China
Zigong Fourth People's Hospital
🇨🇳Zigong, Sichuan, China
Zigong Third People's Hospital
🇨🇳Zigong, Sichuan, China
Ziyang First People's Hospital
🇨🇳Ziyang, Sichuan, China
Kashgar First People's Hospital
🇨🇳Kashgar, Xinjiang, China
Qujing First People's Hospital
🇨🇳Qujing, Yunnan, China
Jinhua Central Hospital
🇨🇳Jinhua, Zhejiang, China
Taizhou First People's Hospital
🇨🇳Taizhou, Zhejiang, China
Yongkang First People's Hospital
🇨🇳Yongkang, Zhejiang, China