Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison/control (C)

Follow-up

Outcome measures and effect size

Comments

Jovin, 2022

(BAOCHE trial)

Type of study:
randomized controlled trial.

Setting and country:
certified stroke centers in China

Funding and conflicts of interest:
Supported by a grant (2016YFC1301502) from the Chinese National Ministry of Science and Technology.

Inclusion criteria:
Patients were eligible for inclusion in the trial if they were 18 to 80 years of age; had an occlusion of the basilar artery or intracranial segments of both vertebral arteries that could be treated within 6 to 24 hours after symptom onset, which was defined as the time at which the patient was last known to be free from acute stroke symptoms except for isolated vertigo; had a prestrioe score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]); and had a score of 10 or higher on the National Institutes of Health Stroke Scale (NIHSS; range, 0 to 42, with higher values indicating more severe deficit) at presentation. Because of slow recruitment, after the enrollment of 61 patients, the inclusion criteria were expanded to allow for the enrollment of patients with an NIHSS score of 6 or higher.

Exclusion criteria:
Patients with evidence of recent intracranial hemorrhage; the presence of a large infarct in the posterior circulation, defined as a posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) of less than 6 (range, 0 to 10, with higher values indicating less infarct burden) on computed tomography (CT), CT angiographic (CTA) source images, or diffusionweighted

magnetic resonance imaging (MRI)8; and the presence on CT, CTA source images, or MRI of a large infarct in the brain stem, defined as a Pons-Midbrain Index of more than 2 points (range, 0 to 8, with higher values indicating more infarct burden; 1 point is attributed to infarction of <50% and 2 points to infarction of ≥50% on one side of the pons or midbrain).

N total at baseline:
Intervention: 110
Control: 107

Important prognostic factors²:

age ± SD
I: 64.2 ± 9.6
C: 63.7 ± 9.8

Sex:
I: 73% M
C: 74% M

Groups comparable at baseline?
Yes

Patients received thrombectomy plus standard medical care (thrombectomy group)

Patients received standard medical care alone (control group).

Length of follow-up:
90 days

Loss-to-follow-up:

Intervention: 1 (0.9%)
Control: 2 (1.9%)

Reasons: withdrawal of consent

Incomplete outcome data:
3 (1.4%)

Reasons: missing primary outcome data.

Functional outcome
Defined by the number of patients who scored mRS 0-2, indicating good clinical outcome.

Effect measure: Risk ratio (RR): 2.79 [1.65 – 1.71] in favor of endovascular therapy.

Mortality
Defined by the incidence of deaths at 90 days.

Effect measure: RR [95% CI]: 1.36 [0.95 - 1.94] in favor of endovascular therapy.

Intracranial haemorrhage
Defined by the number of patients with symptomatic haemorrhage.

Effect measure: RR [95% CI]: 0.19 [0.02 - 1.57] in favor of the control group.

Author’s conclusion
Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages.

Langezaal, 2021

(BASICS trial)

Type of study:
randomized controlled trial.

Setting and country:
23 centers in seven countries.

Funding and conflicts of interest:
Supported by the Dutch Heart Foundation, the Swiss Heart Foundation, the São Paulo Research Foundation, the National Council for Scientific and Technological Development in Brazil, the University Medical Center Utrecht, and St. Antonius Hospital Nieuwegein.

Inclusion criteria:
patients were eligible for inclusion if they were younger than 85 years of age and had acute symptoms and signs compatible with ischemia in the basilar-artery territory, a proven basilar-artery occlusion on computed tomographic (CT) angiography (CTA) or magnetic resonance angiography (MRA), and an NIHSS score of 10 or more.

Exclusion criteria:
Patients with intracranial haemorrhage; extensive, bilateral brainstem infarction on CT; cerebellar mass effect; or acute hydrocephalus evident on neuroimaging were excluded.

N total at baseline:
Intervention: 154
Control: 146

Important prognostic factors²:

age ± SD
I: 66.1 ± 13.1
C: 67. ± 11.9

Sex:
I: 64.9% M
C: 65.8% M

Groups comparable at baseline?
There was an imbalance in the incidence of atrial fibrillation (in 28.6% of the patients in the endovascular group and 15.1% of those in the medical care group); other baseline characteristics were similar in the two groups.

The methods and devices used for endovascular thrombectomy were determined by the local interventional operator. Angioplasty or stenting of the vertebral artery in patients assigned to endovascular therapy was allowed if stenosis hampered access to the basilar artery, and stenting of the basilar artery was allowed if there was residual stenosis after thrombectomy.

Medical care, which consisted of conventional care according to local protocols and national guidelines as determined by the site investigators, could include intravenous thrombolysis.

Length of follow-up:
90 days

Loss-to-follow-up:

Intervention: 0
Control: 0

Incomplete outcome data:
Intervention: 3 (1.9%)
Control: 7 (4.8%)

Reasons: crossover to other treatment.

Functional outcome
Defined by the number of patients who scored mRS 0-2, indicating good clinical outcome.

Effect measure: Risk ratio (RR): 1.15 [0.84 - 1.61] in favor of endovascular therapy.

Mortality
Defined by the incidence of deaths at 90 days.

Effect measure: RR [95% CI]: 1.09 [0.90 - 1.31] in favor of endovascular therapy.

Intracranial haemorrhage
Defined by the number of patients with symptomatic haemorrhage.

Effect measure: RR [95% CI]: 0.96 [0.93 - 1.00] in favor of the control group.

Author’s conclusion:
In patients with basilar-artery occlusion, endovascular therapy and medical therapy were not significantly different with respect to a favorable functional outcome, but the results of our trial could not exclude a benefit of endovascular intervention. Data from larger trials are needed to determine the efficacy and safety of endovascular therapy in patients with basilar-artery occlusion.

Risk of bias
The limitations of our trial include data from screening logs showing that 29.2% of eligible patients were treated outside the trial and that 79.0% of these patients received endovascular therapy, a factor that may have introduced bias in the enrolled population. In addition, 5% of the patients in the medical treatment group crossed over to the endovascular group. We did not use advanced imaging, such as CT perfusion, for patient selection. There was an imbalance of patients with atrial fibrillation in the two treatment groups, but adjustment for this imbalance did not substantially alter effect size between the groups. The NIHSS, which was used for stratification in randomization, is less sensitive to symptoms of posterior-circulation stroke than to those of anterior-circulation stroke. Finally, because recruitment was lower than anticipated, our trial was underpowered for some analyses, including subgroup analyses.

Liu, 2020

(BEST)

Type of study:
multicentre, randomised, open-label trial.

Setting and country:
Multicentre, China.

Funding and conflicts of interest: XinfL reports personal fees from Medtronic and speaker fees from Medtronic, Abbott, and Johnson & Johnson, outside the submitted work. RGN reports personal fees from and collaboration in trials with Stryker Neurovascular, Medtronic, Cerenovus/Neuravi, and Phenox; collaboration in trials from penumbra; and personal fees from Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, and Ceretrieve, outside the submitted work. SD reports grants from the National Health and Medical Research Council of Australia and speaker fees from Abbott, Boehringer Ingelheim, and Medtronic, outside the submitted work; and was on the advisory board of Abbott, Boehringer Ingelheim, and Medtronic. All other authors declare no competing interests.

This trial was funded by an unrestricted grant from the Jiangsu Provincial Special Program of Medical Science (BL2013025).

Inclusion criteria:
Patients were eligible for inclusion in the trial if they had an acute ischaemic stroke consistent with acute occlusion of the basilar artery, could be randomly assigned within 8 h of estimated occlusion time, and had occlusion of the basilar artery confirmed by CT angiography, magnetic resonance angiography, or digital subtraction angiography.Patients with occlusion of the distal intracranial vertebral artery (V4 segment) resulting in no flow to the basilar artery (eg, functional basilar artery occlusion)

were also included in the trial. Other inclusion criteria were age 18 years or older, a prestroke score of 0–2 on the modified Rankin scale (mRS; range 0–6, with a score of 0 indicating no disability and higher scores indicating more severe disability), and no evidence of intracranial haemorrhage, significant cerebellar mass effect, acute hydrocephalus, or extensive bilateral brainstem ischaemia on CT or MRI

Exclusion criteria:
n.r.

N total at baseline:
Intervention: 66 Control: 65

Important prognostic factors²:
age (IQR):
I: 62 (50-74)
C: 68 (57-74)

Sex:
I: 73% M
C: 80% M

Stroke diagnosis:
I: 86% HI, 14% HB
C: 85% HI, 15% HB

Groups comparable at baseline?
Yes

In the intervention group, endovascular preparation was initiated simultaneously with or soon after intravenous alteplase administration was started. The endovascular procedure consisted of mechanical thrombectomy with stent retriever (the preferred method) or thrombo-aspiration devices. Patients in both groups were admitted to stroke units or intensive care units and received standard medical therapy, which followed the American Heart Association/American Stroke Association guidelines.

The control group received standard medical therapy which followed the American Heart Association/American Stroke Association guidelines

Length of follow-up:
90 days

Loss-to-follow-up:

Intervention: 0
Control: 0

Incomplete outcome data:
Intervention: 3 (4.5%)
Reasons: Did not receive intervention due to not suitable for endovascular treatment and death before intervention.

Control: 14 (21.5%)
Reasons: Patients or family did not accept medical therapy.

Functional outcome.
Defined by the number of patients who scored mRS 0-2, indicating good clinical outcome.

Effect measure: Risk ratio (RR) [95% CI]: 1.20 [ 0.72 - 2.03] favoring endovascular therapy.

Mortality
Defined by the incidence of deaths at 90 days.

Effect measure: RR [95% CI]: 1.08 [0.84 - 1.40] favoring endovascular therapy.

Intracranial haemorrhage
Defined by the number of patients with symptomatic haemorrhage.

Effect measure: RR [95% CI]: 0.92 [0.86 to 1.00] in favor of the control group.

Author’s conclusion:
In conclusion, our study did not provide evidence of a difference in favourable neurological outcomes in patients treated with endovascular therapy plus standard medical therapy compared with those treated with standard medical therapy alone. Our results might have been confounded by its reduced sample size and the poor adherence to the assigned study treatment, because patients with basilar artery occlusion who were treated with thrombectomy had better outcomes than those who received standard medical therapy alone.

Risk of bias
However, our results might have been confounded by the fact that equipoise was lost over the course of the study, as shown by the high crossover rates and progressive drop in the average rate of valid per-centre recruitment, which eventually led to the early termination of the trial. This limited our final sample size to only 131 (38%) of our planned target of 344 patients, resulting in an underpowered analysis. Moreover, as suggested by the per-protocol and as-treated analyses, our high rate of crossovers (17 [13%] of 131 patients) might have lowered the treatment effect size. This culminated at a 10% difference in the rate of mRS 0–3 at 90 days, which was lower than our initial assumption of a 15% difference. Finally, the fact that a third of the qualifying patients declined trial participation might have introduced selection biases that also contributed to our negative findings.

Tao, 2022

(ATTENTION)

Type of study:
randomized controlled trial.

Setting and country:
multicenter, prospective, randomized, open-label trial at 36 centers in China

Funding and conflicts of interest:
Supported by the Program for Innovative Research Team of the First Affiliated Hospital of the University of Science and Technology of China, the Beijing Dingyi Foundation (China Special Fund for Stroke Prevention and Treatment), and the Beijing Healthunion Cardio-Cerebrovascular Disease Prevention and Treatment Foundation.

Inclusion criteria:
Patients were eligible for enrollment if they were 18 years of age or older and had had a moderate to- severe acute ischemic stroke consistent with basilar-artery occlusion. A moderate-to-severe acute ischemic stroke was defined by a score of 10 or higher on the National Institutes of Health Stroke Scale (NIHSS; range, 0 to 42, with higher scores indicating greater neurologic deficits) at the time of neuroimaging.

Exclusion criteria:
prestroke score, assessed retrospectively, of at least 3 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death) among those younger than 80 years of age or a modified Rankin scale score of at least 1 among those 80 years of age or older; if they had intracranial hemorrhage on neuroimaging; or if they had a posterior circulation Alberta Stroke Program Early Computed Tomography Score (PC-ASPECTS) of less than 6 points among patients younger than 80 years of age and of less than 8 points among those 80 years of age or older.

N total at baseline:
Intervention: 226
Control: 114

Important prognostic factors²:

age ± SD
I: 66 ± 11.1
C: 67.3 ± 10.2

Sex:
I: 66% M
C: 72% M

Groups comparable at baseline?
Yes

The strategies that were used for endovascular treatment included stent retrievers, thromboaspiration, balloon angioplasty, stent deployment, intraarterial thrombolysis (with alteplase or urokinase), or combinations of these approaches that were left to the discretion of the treating team.

The standard care for acute basilar-artery occlusion in China is that patients arriving at a hospital within 4.5 hours after stroke onset receive intravenous thrombolysis.

Length of follow-up:
90 days

Loss-to-follow-up:

Intervention: 2 (0.9%)
Control: 0 (0%)

Reasons: withdrawal of consent

Incomplete outcome data:
n.r.

Functional outcome
Defined by the number of patients who scored mRS 0-2, indicating good clinical outcome.

Effect measure: Risk ratio (RR): 1.64 [1.09 – 2.48] in favor of endovascular therapy.

Mortality
Defined by the incidence of deaths at 90 days.

Effect measure: RR [95% CI]: 1.50 [1.19 - 1.91] in favor of endovascular therapy.

Intracranial haemorrhage
Defined by the number of patients with symptomatic haemorrhage.

Effect measure: RR [95% CI]: 0.08 [0.04 – 0.44] in favor of the control group.

Author’s conclusion
In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Jovin, 2022

(BAOCHE trial)

Definitely yes;

Reason: Patients were randomly assigned in a 1:1 ratio to undergo thrombectomy plus receive standard medical care (thrombectomy group) or to receive standard medical care alone (control group). Randomization was performed by means of a central, Web-based procedure, with the use of a minimization process to balance the two treatment groups and with stratification according to age (≤70 years or >70 years), the time from symptom onset to randomization (6 to 12 hours or >12 to 24 hours), and baseline NIHSS score (6 to 20 or >20).

No information;

Reason: No information was provided about allocation concealment.

Probably no;

Reason: Only information was provided about blinding of outcome evaluation (which was made sure). Considering that blinding to treatment type was quite difficult to achieve, there was definitely performance bias due to difficulty of blinding to treatment type for patients, healthcare providers and data analysts.

Definitely yes;

Reason: There were few losses to follow-up (1.4%).

Definitely no;

Reason: Protocol changes were made during the trial, most notably to the primary outcome, on the basis of data from other trials that were unavailable at the time of the protocol design.

Probably no;

Reason: Since the population that was enrolled is representative of the Han Chinese population, the generalizability of our trial results to other populations is limited.

Moderate

Langezaal, 2021

(BASICS trial)

Definitely yes;

Reason: Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy or standard medical care. Randomization was conducted with the use of a central, Web-based procedure with permuted blocks (size 2) and was stratified according to center, use of intravenous thrombolysis, and NIHSS score (<20 or ≥20).

No information;

Reason: No information was provided about the concealment of allocation.

Probably no;

Reason: The assessment of endpoints was blinded. Considering that blinding to treatment type was quite difficult to achieve, there was definitely performance bias due to difficulty of blinding to treatment type for patients, healthcare providers and data analysts.

Definitely yes;

Reason: There were few losses to follow-up (<1%).

Definitely yes;

Reason: All the authors vouch for the accuracy and completeness of the presented data, for adherence of the trial to the protocol, and for the accurate reporting of adverse events. The trial was monitored by an independent data and safety monitoring board.

Definitely no;

Reason: The enrolled population derived from inside and outside the trial, crossing over of patients occurred in 5% in the medical treatment group, there was an inbalance of patients with atrial fibrillation in the two groups.

Moderate

Liu, 2020

(BEST trial)

Definitely yes;

Reason: The randomisation sequence was computer generated (SAS Statistical Package, version 9.3) and stratified by participating centres.

Definitely yes;

Reason: Allocation concealment was done by a statistician who did not directly participate in trial recruitment and enrolment. Allocation concealment was implemented by use of sealed envelopes., centralised, webbased randomisation system.

Probably no;

Reason: The assessment of endpoints was blinded. Considering that blinding to treatment type was quite difficult to achieve, there was definitely performance bias due to difficulty of blinding to treatment type for patients, healthcare providers and data analysts.

Definitely yes;

Reason: There was no lost to follow-up.

Definitely yes;

Reason: The safety endpoints were adjudicated by an independent clinical-events committee. The trial was terminated early due to reaching clinically predefined endpoints.

Definitely no;

Reason: A third of the qualifying patients declined trial participation and high crossover rates might have induced confounding of the results.

Moderate

Tao, 2022

(ATTENTION trial)

Definitely yes;

Reason: Patients were randomly assigned in a 2:1 ratio to undergo endovascular thrombectomy and receive best medical care (thrombectomy group) or to receive best medical care alone (control group). Randomization was performed as soon as possible after the occlusion of the basilar artery had been confirmed on imaging at trial hospitals and written informed consent for trial participation had been obtained.

Definitely no;

Reason: Owing to the nature of the intervention, treatment assignments were not concealed from patients or the treating team.

Probably no;

Reason: Only outcome assessors were blinded.

Considering that blinding to treatment type was quite difficult to achieve, there was definitely performance bias due to difficulty of blinding to treatment type for patients, healthcare providers. 

Definitely yes;

Reason: No patients were lost to follow-up or had data missing for main baseline covariates and primary outcome. 

Definitely yes;

Reason: The authors vouch for the accuracy and completeness of the presented data, for the fidelity of the trial to the protocol, and for the accurate reporting of adverse events.

Definitely no;

Reason: Chinese patients have a high prevalence of intracranial large-artery atherosclerosis, and our results may not be generalizable to Western countries.

Moderate