← Back
NeuroTrials.ai
Neurology Clinical Trial Database

TREND

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial

Share Share Copied! Compare

Year of Publication: 2023

Authors: Wenbo Zhao, MD; Sijie Li, MD; Chuanhui Li, ..., MD; Xunming JI

Journal: JAMA Neurology

Citation: JAMA Neurol. 2024;81(5):e235882. DOI:10.1001/jamaneurol.2023.5882

Link: https://jamanetwork.com/journals/jamaneu...article/2814889

Clinical Question

To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin.

Bottom Line

Intravenous tirofiban significantly reduced the incidence of early neurological deterioration within 72 hours in patients with acute noncardioembolic ischemic stroke compared to oral aspirin. This improvement translated to a higher rate of excellent functional outcomes at 90 days, without a significant increase in symptomatic intracranial hemorrhage or major extracranial bleeding.

Major Points

  • 425 patients with acute noncardioembolic stroke were randomized (213 to tirofiban, 212 to aspirin).
  • The primary outcome (early neurological deterioration within 72 hours) occurred in 11.0% (28/254) in the tirofiban group vs 20.9% (53/254) in the aspirin group (adjusted relative risk [aRR], 0.54; 95% CI, 0.35-0.83; P=0.005).
  • Excellent functional outcome (mRS 0-1) at 90 days was significantly higher in the tirofiban group (56.7% vs 46.1%; aRR, 1.23; 95% CI, 1.01-1.50; P=0.038).
  • The incidence of symptomatic intracranial hemorrhage was 1.2% (3/254) in the tirofiban group vs 0.8% (2/254) in the aspirin group (aRR, 1.41; 95% CI, 0.24-8.19; P=0.71).
  • Major extracranial bleeding occurred in 0.8% (2/254) in the tirofiban group vs 0.4% (1/254) in the aspirin group (aRR, 1.70; 95% CI, 0.16-17.75; P=0.66).
  • No significant difference in 90-day mortality (8.3% tirofiban vs 9.1% aspirin; aRR, 0.94; 95% CI, 0.53-1.66; P=0.83).

Design

Study Type: Investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment

Randomization: 1

Blinding: Blinded end-point assessment (outcome assessors were blinded to treatment assignment).

Enrollment Period: September 2020 to March 2023

Follow-up Duration: 90 days (primary outcome)

Centers: 10

Countries: China

Sample Size: 508

Analysis: Intention-to-treat (ITT) population for primary and secondary efficacy outcomes; safety outcomes analyzed in the safety population. Primary outcome analyzed using multivariable logistic regression adjusted for baseline NIHSS score, age, and presence of large artery atherosclerosis. Binary outcomes compared using relative risk ratios. Ordinal shift on mRS analyzed using unadjusted common odds ratios. Sensitivity analyses using per-protocol analysis and adjustment for other variables. Statistical analysis using SAS, version 9.4.

Inclusion Criteria

  • Patients aged 18 to 80 years with acute noncardioembolic stroke.
  • Stroke onset within 24 hours.
  • National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20.
  • Patients with intracranial large-artery atherosclerosis confirmed by CT angiography, MR angiography, or digital subtraction angiography.
  • Patients with atrial fibrillation were excluded, and other cardioembolic sources were excluded by clinical judgment and transthoracic echocardiography.
  • Patients were included with no previous mRS score >1.

Exclusion Criteria

  • Known intracranial hemorrhage on brain imaging.
  • Major stroke (NIHSS score >20).
  • Tandem occlusion or other intracranial vascular malformations.
  • Contraindications to antiplatelet therapy or to tirofiban.
  • Concomitant use of any other antiplatelet agent (excluding aspirin for the tirofiban group) or anticoagulant therapy.
  • History of major bleeding in the last 3 months.
  • Hypersensitivity to tirofiban or aspirin.
  • Pregnancy or lactation.

Arms

FieldTirofiban GroupControl
InterventionIntravenous tirofiban (10 μg/kg bolus, then 0.15 μg/kg per minute infusion for 12 hours) within 24 hours of stroke onset, in addition to oral aspirin (100 mg daily) initiated immediately after bolus.Oral aspirin (100 mg daily) initiated within 24 hours of stroke onset, plus placebo intravenous infusion.
Duration12-hour infusion (followed by 90-day follow-up)90 days

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Early neurological deterioration (END) within 72 hours of stroke onset, defined as an increase of ≥2 points in the total NIHSS score or ≥1 point in motor NIHSS score from baseline within 72 hours, or death within 72 hours.Primary20.9% (53/254 patients)11.0% (28/254 patients)0.540.005
Excellent functional outcome (mRS 0-1) at 90 daysSecondary46.1% (117/254 patients)56.7% (144/254 patients)1.230.038
Good functional outcome (mRS 0-2) at 90 daysSecondary53.5% (136/254 patients)64.2% (163/254 patients)1.20.024
Shift on mRS at 90 days (ordinal analysis)SecondaryMedian -1 (IQR -3 to 1)Median -2 (IQR -4 to 0)1.480.003
90-day mortalitySecondary9.1% (23/254 patients)8.3% (21/254 patients)0.940.83
Recanalization on 24-h MRA/CTASecondary27.6% (70/254 patients)32.7% (83/254 patients)1.210.20
Any new lesion on 24-h DWISecondary27.2% (69/254 patients)28.7% (73/254 patients)1.050.71

Criticisms

  • The trial was open-label, meaning patients and investigators were aware of the treatment assignment, which could introduce bias, though outcome assessors were blinded.
  • The study focused on a Chinese population, which may limit generalizability to other ethnic groups.
  • The study did not perform a long-term follow-up beyond 90 days, so the sustained effects of tirofiban are unknown.
  • The study excluded patients with severe stroke (NIHSS >20) and cardioembolic stroke, limiting generalizability to these patient populations.
  • The rates of sICH and major extracranial hemorrhage were numerically higher in the tirofiban group, although not statistically significant in the main analysis. This warrants caution.

Subgroup Analysis

Subgroup analyses were conducted for the primary outcome based on age (<65 vs. ≥65 years), sex, baseline NIHSS score (4-9 vs. 10-20), time from LKN to randomization (≤12 vs. >12 hours), LVO on CTA/MRA (yes vs. no), and ASPECTS (7-10 vs. ≤6). No significant treatment effect modification was observed across any prespecified subgroups for primary, secondary, or safety outcomes.

Funding

National Natural Science Foundation of China and Beijing Natural Science Foundation.

Based on: TREND (JAMA Neurology, 2023)

Authors: Wenbo Zhao, MD; Sijie Li, MD; Chuanhui Li, ..., MD; Xunming JI

Citation: JAMA Neurol. 2024;81(5):e235882. DOI:10.1001/jamaneurol.2023.5882

Content summarized and formatted by NeuroTrials.ai.