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CLOTBUST-ER

Combined Lysis of Thrombus With Ultrasound and Systemic tPA for Emergent Revascularization in Acute Ischemic Stroke–Enhanced Regimen

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Year of Publication: 2019

Authors: Andrei V. Alexandrov, Georgios Tsivgoulis, Haralampos Milionis, et al.

Journal: Stroke

Citation: Stroke. 2019;50:351-354. doi:10.1161/STROKEAHA.118.023687

Link: https://doi.org/10.1161/STROKEAHA.118.023687

Clinical Question

Does adding 2 hours of transcranial ultrasound to IV tPA improve functional outcomes in acute ischemic stroke compared to tPA alone?

Bottom Line

In this prematurely terminated trial, ultrasound plus tPA did not significantly improve 90-day functional independence versus tPA alone, but was safe without increasing sICH.

        Major Points
        Planned 830 patient enrollment; stopped after 126 due to slow recruitment
Randomized 1:1 to tPA + ultrasound vs tPA + sham
Primary endpoint: mRS 0–1 at 90 days (33% vs 29%, OR 1.14, p=0.70)
Symptomatic ICH: 3% in each arm
Mortality: 8% (ultrasound) vs 10% (sham)
NIHSS median 16; median onset-to-tPA time ~150 minutes

      

Design

Study Type: Multicenter, randomized, blinded-endpoint, sham-controlled trial

Randomization: 1

Blinding: Outcome assessors blinded; patients and treating teams not blinded to ultrasound

Enrollment Period: 2013–2015

Follow-up Duration: 90 days

Centers: 10

Countries: USA, Europe

Sample Size: 126

Analysis: Intention-to-treat; logistic regression adjusted for baseline NIHSS and age

Inclusion Criteria

Age ≥18 years
Acute ischemic stroke within 3 hours of onset
NIHSS ≥10
Eligible for standard IV tPA

Exclusion Criteria

Contraindications to tPA
Large established infarct on imaging
Inability to insonate temporal bone window
Prior intracranial hemorrhage

Arms

Field	tPA + Ultrasound	Control
Intervention	Standard IV alteplase plus 2-hour continuous 2-MHz transcranial Doppler insonation of occluded artery	Standard IV alteplase plus sham insonation
Duration	Single acute treatment	Single acute treatment

Outcomes

Outcome	Type	Control	Intervention	P-value
mRS 0–1 at 90 days	Primary	29%	33%	0.70
Symptomatic ICH	Secondary	3%	3%	1.00
Mortality	Secondary	10%	8%	0.75
Symptomatic ICH	Adverse	3%	3%
Any ICH	Adverse	8%	10%

Subgroup Analysis

No significant treatment interaction by occlusion site, baseline NIHSS, or time to treatment

Criticisms

Terminated early with only 15% of planned enrollment, underpowered
No blinding of treating clinicians
High rate of technical exclusions due to poor bone window
Findings not generalizable to patients without adequate insonation window

Funding

National Institute of Neurological Disorders and Stroke

Based on: CLOTBUST-ER (Stroke, 2019)

Authors: Andrei V. Alexandrov, Georgios Tsivgoulis, Haralampos Milionis, et al.

Citation: Stroke. 2019;50:351-354. doi:10.1161/STROKEAHA.118.023687

Content summarized and formatted by NeuroTrials.ai.

CLOTBUST-ER

(2019)

Objective

Transcranial ultrasound plus IV tPA vs tPA alone to improve functional outcomes in acute ischemic stroke.

Study Summary

• Trial stopped early after enrolling 20% of planned sample size due to slow recruitment
• No significant difference in 90-day mRS 0–1 between ultrasound+tPA and tPA alone
• Safety profile similar, with no excess in symptomatic ICH

Intervention

Multicenter, randomized, blinded-endpoint trial comparing 2-hour 2-MHz transcranial Doppler ultrasound plus standard IV tPA vs sham ultrasound plus tPA. Planned enrollment 830 patients; actual enrollment 126 before termination.

Inclusion Criteria

• Age ≥18 years
• Acute ischemic stroke ≤3 h from onset
• NIHSS ≥10
• Eligible for IV tPA per guidelines

Study Design

Arms: tPA + ultrasound, tPA + sham ultrasound

Patients per Arm: Ultrasound: 63, Sham: 63

Outcome

• mRS 0–1 at 90 days: 33% (ultrasound) vs 29% (sham), OR 1.14, p=0.70
• Symptomatic ICH: 3% vs 3%
• Mortality: 8% vs 10%

Bottom Line

In this prematurely terminated trial, ultrasound plus tPA did not significantly improve 90-day functional independence versus tPA alone, but was safe without increasing sICH.

Major Points

Planned 830 patient enrollment; stopped after 126 due to slow recruitment
Randomized 1:1 to tPA + ultrasound vs tPA + sham
Primary endpoint: mRS 0–1 at 90 days (33% vs 29%, OR 1.14, p=0.70)
Symptomatic ICH: 3% in each arm
Mortality: 8% (ultrasound) vs 10% (sham)
NIHSS median 16; median onset-to-tPA time ~150 minutes

Study Design

Study Type: Multicenter, randomized, blinded-endpoint, sham-controlled trial
Randomization: Yes
Blinding: Outcome assessors blinded; patients and treating teams not blinded to ultrasound
Sample Size: 126
Follow-up: 90 days
Centers: 10
Countries: USA, Europe

Primary Outcome

Definition: mRS 0–1 at 90 days

Control	Intervention	HR/OR	P-value
29%	33%	- (0.54–2.41)	0.70

Limitations & Criticisms

Terminated early with only 15% of planned enrollment, underpowered
No blinding of treating clinicians
High rate of technical exclusions due to poor bone window
Findings not generalizable to patients without adequate insonation window

Citation

Stroke. 2019;50:351-354. doi:10.1161/STROKEAHA.118.023687

View Original Publication →

CLOTBUST-ER

Combined Lysis of Thrombus With Ultrasound and Systemic tPA for Emergent Revascularization in Acute Ischemic Stroke–Enhanced Regimen

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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