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CHOICE

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial

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Year of Publication: 2022

Authors: Arturo Renú, Mónica Millán, Luis San Román, ..., Ángel Chamorro

Journal: JAMA

Citation: JAMA. 2022;327(9):826-835.

Link: https://doi.org/10.1001/jama.2022.1645

PDF: https://jamanetwork.com/journals/jama/ar...50100.36983.pdf

Clinical Question

Does adjunct intra-arterial alteplase after successful thrombectomy improve functional outcomes in patients with large vessel occlusion acute ischemic stroke?

Bottom Line

Intra-arterial alteplase after successful thrombectomy significantly increased the likelihood of excellent 90-day functional outcome (mRS 0–1), but the trial was underpowered due to early termination and its findings are preliminary.

        Major Points
        CHOICE was a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial conducted at 7 stroke centers in Catalonia, Spain.
Included patients had large vessel occlusion stroke treated with thrombectomy within 24 hours and achieved reperfusion (eTICI ≥2b50).
Patients were randomized to receive intra-arterial alteplase (0.225 mg/kg, max 22.5 mg) or placebo infused over 15–30 minutes after thrombectomy.
The trial was stopped early after enrolling 121 patients due to COVID-19-related logistical limitations.
Primary outcome (mRS 0–1 at 90 days): 59.0% in alteplase group vs 40.4% in placebo (adjusted RD 18.4%; 95% CI, 0.3%–36.4%; P = 0.047).
No symptomatic ICH in alteplase group vs 3.8% in placebo group.
No significant differences in mRS shift analysis, infarct volume, or quality of life metrics.

      

Design

Study Type: Phase 2b, randomized, double-blind, placebo-controlled trial

Randomization: 1

Blinding: Double-blind (participants and assessors)

Enrollment Period: December 2018 to May 2021

Follow-up Duration: 90 days

Centers: 7

Countries: Spain

Sample Size: 121

Analysis: Binomial regression for primary outcome (adjusted for prior IV alteplase), proportional odds logistic regression for mRS shift; sensitivity and subgroup analyses included.

Inclusion Criteria

Acute ischemic stroke due to large vessel occlusion (anterior, middle, or posterior cerebral artery)
Treated with thrombectomy within 24 hours
Post-thrombectomy eTICI score of 2b50 or higher
Age ≥18 years
Pre-stroke independence (mRS ≤1)

Exclusion Criteria

Contraindication to IV alteplase (excluding time-based)
NIHSS >25 at admission
Complete recovery in angiography suite
Other standard exclusions listed in Supplement (e.g., recent anticoagulant use, severe comorbidity)

Baseline Characteristics

Characteristic	Control	Active
Age, median (IQR), y	73 (69–77)	73 (71–76)
Female, %	46%	46%
NIHSS, median (IQR)	14 (10–20)	14 (8–20)
IV alteplase before randomization	60%	62%
Glucose, median (IQR), mg/dL	119 (103–143)	134 (108–164)
Hypertension	65%	64%
Diabetes	21%	31%
ASPECTS, median (IQR)	10 (8–10)	9 (9–10)

Arms

Field	Control	Alteplase
Intervention	Intra-arterial placebo infusion over 15–30 minutes after thrombectomy	Intra-arterial alteplase 0.225 mg/kg (max 22.5 mg) infused over 15–30 minutes after thrombectomy
Duration	Single infusion (15–30 minutes)	Single infusion (15–30 minutes)

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Proportion of patients with mRS 0–1 at 90 days	Primary	40.4%	59.0%		0.047
mRS shift analysis	Secondary			OR 1.54 (95% CI, 0.79–2.94)	0.38
Barthel Index 95–100 at 90 days	Secondary	61.4%	67.9%		0.60
EQ-5D-3L VAS at 90 days	Secondary	80 (IQR 50–90)	80 (IQR 60–90)		0.88
Symptomatic ICH	Adverse	3.8%	0%
Death at 90 days	Adverse	15.4%	8.2%

Subgroup Analysis

No statistically significant treatment interaction in subgroups (IV alteplase use, sex, glucose >100 mg/dL, time to groin puncture, eTICI score).

Criticisms

Trial stopped early (60% enrolled) due to COVID-19 disruptions, reducing statistical power.
Wide confidence interval for the primary endpoint (0.3% to 36.4%) limits precision.
Only 7% of thrombectomy-treated patients were included, limiting generalizability.
No benefit seen in shift analysis or infarct volume metrics.
No multiple testing correction for secondary endpoints.

Funding

Fundació La Marató de TV3, Spanish Ministry of Health, European Regional Development Fund. Drug/placebo provided by Boehringer Ingelheim.

Based on: CHOICE (JAMA, 2022)

Authors: Arturo Renú, Mónica Millán, Luis San Román, ..., Ángel Chamorro

Citation: JAMA. 2022;327(9):826-835.

Content summarized and formatted by NeuroTrials.ai.

CHOICE

(2022)

Objective

To assess whether adjunct intra-arterial alteplase after successful thrombectomy improves 90-day functional outcomes in patients with acute ischemic stroke due to large vessel occlusion.

Study Summary

• In patients with acute ischemic stroke and successful reperfusion (eTICI 2b50–3) after thrombectomy, intra-arterial alteplase (0.225 mg/kg) significantly increased the rate of excellent outcome (mRS 0–1) at 90 days versus placebo. The study was prematurely terminated due to COVID-19 constraints and placebo supply expiration.

Intervention

Intra-arterial alteplase (0.225 mg/kg, max 22.5 mg) vs placebo, infused over 15–30 minutes following thrombectomy.

Inclusion Criteria

Adults ≥18 years with acute ischemic stroke and large vessel occlusion (anterior, middle, or posterior cerebral artery), treated with thrombectomy within 24 hours and achieving eTICI 2b50–3. ASPECTS ≥6 if <4.5h from onset, or perfusion/DWI-MRI selection if later.

Study Design

Arms: IA alteplase (n=61) vs IA placebo (n=52)

Patients per Arm: IA alteplase: 61, IA placebo: 52

Outcome

• Primary: mRS 0–1 at 90 days: 59.0% (alteplase) vs 40.4% (placebo); adjusted RD 18.4% (95% CI, 0.3–36.4); P=0.047.<br>• sICH: 0% vs 3.8%.<br>• Mortality at 90 days: 8.2% vs 15.4%.<br>• No significant differences in angiographic improvement, infarct expansion, or 90-day infarct volume. Shift analysis not significant.

Bottom Line

Major Points

CHOICE was a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial conducted at 7 stroke centers in Catalonia, Spain.
Included patients had large vessel occlusion stroke treated with thrombectomy within 24 hours and achieved reperfusion (eTICI ≥2b50).
Patients were randomized to receive intra-arterial alteplase (0.225 mg/kg, max 22.5 mg) or placebo infused over 15–30 minutes after thrombectomy.
The trial was stopped early after enrolling 121 patients due to COVID-19-related logistical limitations.
Primary outcome (mRS 0–1 at 90 days): 59.0% in alteplase group vs 40.4% in placebo (adjusted RD 18.4%; 95% CI, 0.3%–36.4%; P = 0.047).
No symptomatic ICH in alteplase group vs 3.8% in placebo group.
No significant differences in mRS shift analysis, infarct volume, or quality of life metrics.

Study Design

Study Type: Phase 2b, randomized, double-blind, placebo-controlled trial
Randomization: Yes
Blinding: Double-blind (participants and assessors)
Sample Size: 121
Follow-up: 90 days
Centers: 7
Countries: Spain

Primary Outcome

Definition: Proportion of patients with mRS 0–1 at 90 days

Control	Intervention	HR/OR	P-value
40.4%	59.0%	- (0.3% to 36.4%)	0.047

Limitations & Criticisms

Trial stopped early (60% enrolled) due to COVID-19 disruptions, reducing statistical power.
Wide confidence interval for the primary endpoint (0.3% to 36.4%) limits precision.
Only 7% of thrombectomy-treated patients were included, limiting generalizability.
No benefit seen in shift analysis or infarct volume metrics.
No multiple testing correction for secondary endpoints.

Citation

JAMA. 2022;327(9):826-835.

View Original Publication →

CHOICE

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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