Adjunct tirofiban treatment after successful endovascular thrombectomy recanalisation in acute anterior circulation ischemic stroke (ATTRACTION): protocol of a multicenter, prospective, double-blind, randomised trial

The ATTRACTION trial is a multicenter, prospective, double-blind, randomized study designed to evaluate the safety and efficacy of adjunct tirofiban therapy versus placebo in improving 90-day functional outcomes for patients with anterior circulation large vessel occlusion strokes who achieve successful recanalization following endovascular thrombectomy.

The Gist

Imagine your brain is a bustling city, and its streets are the blood vessels that deliver oxygen and nutrients. Sometimes, a massive truck (a blood clot) gets stuck in a major highway, blocking traffic and causing a traffic jam that threatens to shut down the city. This is a large vessel occlusion stroke.

For years, doctors have had a powerful tool called Endovascular Thrombectomy (EVT). Think of this as a specialized tow truck that drives right up to the stuck truck and pulls it out. This procedure is a miracle; it clears the blockage in over 70% of cases.

But here's the problem: Even after the tow truck clears the main road, the city doesn't always bounce back. Why? Because the "side streets" (tiny capillaries) are still clogged with debris, or the road surface is so damaged that traffic starts jamming up again immediately. In medical terms, this is called "futile recanalization." The road is open, but the city is still in trouble.

The New Idea: The "Traffic Police" (Tirofiban)

The ATTRACTION trial is a massive new study asking a simple question: What if we send in a specialized traffic police force immediately after the tow truck leaves to keep the roads clear?

This "traffic police" is a drug called Tirofiban.

• How it works: Unlike other drugs that try to dissolve the clot (like a chemical solvent), Tirofiban acts like a "peacekeeper." It stops the tiny cars (platelets) from sticking together and forming new traffic jams right on the freshly cleared road.
• The Goal: To see if adding this "peacekeeper" helps more patients walk out of the hospital and return to their normal lives.

How the Study Works (The Experiment)

The researchers are running a giant, fair test across about 80 hospitals in China. Here is the setup:

1. The Players: They are looking for 1,360 patients who have just had their "tow truck" (EVT) successfully clear the main highway.
2. The Coin Flip: Once the road is clear, the patient is randomly assigned to one of two groups, like flipping a coin:
   • Group A (The Treatment): Gets the Tirofiban "peacekeeper" drug.
   • Group B (The Control): Gets a "fake" drug (placebo), which looks and tastes exactly the same but does nothing.
3. The Blindfold: Neither the doctors nor the patients know who got which drug. This ensures the results are honest and not influenced by expectations.
4. The Check-up: They will wait 90 days (about three months) to see who recovered better.

What Are They Looking For?

• The Good News (Efficacy): Did the patients in the Tirofiban group end up with a Modified Rankin Scale (mRS) score of 0–2?
  • Simple translation: This is a score from 0 (perfect health) to 6 (death). A score of 0–2 means the patient is back to their normal life or has only very minor disabilities. They can walk, talk, and take care of themselves.
• The Safety Check: The biggest worry with any new drug for stroke is bleeding. The study is closely watching to see if the "peacekeeper" causes dangerous brain bleeds (hemorrhage) in the first 48 hours.

Why Does This Matter?

Right now, we have a great tow truck (EVT), but we don't have a perfect strategy for what happens immediately after the tow truck leaves. Some previous studies tried using different drugs (like dissolving agents), but the results were mixed—sometimes they helped, sometimes they caused too much bleeding.

Tirofiban is different. It doesn't dissolve the clot; it just stops new ones from forming. If this study proves that Tirofiban is safe and effective, it could become the new standard of care. It would mean that for every major stroke where the blockage is cleared, we have a proven way to ensure the "city" stays open and the patient recovers fully.

In short: The ATTRACTION trial is a giant, scientific experiment to see if a specific "traffic police" drug can turn a "successful rescue" into a "full recovery" for stroke patients.

Technical Summary

Based on the provided preprint, here is a detailed technical summary of the ATTRACTION trial protocol.

1. Problem Statement

Despite the establishment of Endovascular Thrombectomy (EVT) as the standard of care for acute anterior circulation large vessel occlusion (LVO) ischemic stroke, a significant clinical gap remains:

• The "Futile Recanalization" Phenomenon: While EVT achieves successful recanalization (mTICI 2b-3) in >70% of patients, only 40–50% achieve functional independence (modified Rankin Scale [mRS] 0–2) at 90 days.
• Unmet Need: This discrepancy is attributed to multifactorial reperfusion failure, including microcirculatory dysfunction, distal embolization, and re-occlusion.
• Limitations of Current Adjuncts: Previous trials investigating adjunctive intra-arterial thrombolysis (e.g., alteplase, tenecteplase) have yielded conflicting results, with some showing benefit and others showing no effect or increased bleeding risks.
• Theoretical Gap: There is a lack of robust evidence regarding the use of tirofiban, a glycoprotein (GP) IIb/IIIa inhibitor, specifically for preventing re-occlusion and treating microvascular dysfunction after successful recanalization. Unlike fibrinolytics, tirofiban targets platelet aggregation without thrombolytic properties.

2. Methodology

The ATTRACTION trial is designed as a multicenter, prospective, double-blind, randomized, controlled trial (RCT) conducted across approximately 80 clinical centers in China.

• Study Population:
  • Inclusion: Adults with acute anterior circulation LVO stroke who have achieved successful recanalization (mTICI 2b-3) via EVT within 24 hours of symptom onset.
  • Eligibility: Includes patients with tandem occlusions and those who received prior intravenous thrombolysis (IVT).
  • Exclusion: Patients receiving intra-arterial thrombolysis (including intra-arterial tirofiban) during the procedure.
• Randomization & Blinding:
  • Ratio: 1:1 allocation to Tirofiban vs. Placebo.
  • Method: Centralized 24/7 network system with block randomization (block size 4), stratified by clinical center.
  • Blinding: Double-blind (investigators, patients, and outcome assessors are unaware of assignment). Unblinding is permitted only for safety emergencies.
• Intervention:
  • Tirofiban Group: Receives an intra-arterial bolus of tirofiban (5 µg/kg, max 0.5 mg) followed by a continuous intravenous infusion (0.1 µg/kg/min) for up to 24 hours.
  • Placebo Group: Receives normal saline via the same infusion protocol and volume.
  • Timing: Infusion begins immediately after randomization (post-EVT confirmation of mTICI 2b-3).
• Outcomes:
  • Primary Efficacy: Proportion of patients with an mRS score of 0–2 at 90 days (±7 days).
  • Primary Safety: Proportion of symptomatic intracranial hemorrhage (sICH) within 48 hours of randomization (defined by Heidelberg Bleeding Classification).
  • Secondary Outcomes: mRS 0–1 and 0–3 at 90 days, mRS shift analysis, NIHSS improvement at 36 hours, EQ-5D-5L scores, all-cause mortality, and any intracranial hemorrhage.
• Sample Size:
  • Target enrollment: 1,360 patients (680 per arm).
  • Power Calculation: Based on an assumed 44.0% success rate in the placebo group (derived from RESCUE BT subgroup analysis) and an expected 8% absolute improvement in the tirofiban group.
  • Parameters: 80% power, 5% two-sided type I error, accounting for 10% loss to follow-up.
• Statistical Analysis:
  • Primary Analysis: Intention-to-treat (Full Analysis Set) using a modified Poisson regression model to estimate Risk Ratios (RR) with 95% Confidence Intervals (CI).
  • Adjustments: Covariates include age, baseline NIHSS, ASPECTS, occlusion site, and time from last known well.
  • Subgroup Analyses: Planned for age, sex, time window, stroke severity, etiology (including cardioembolism), and rescue therapy requirements.

3. Key Contributions

• First Large-Scale RCT on Post-EVT Tirofiban: ATTRACTION is the largest randomized trial specifically designed to evaluate the safety and efficacy of sequential tirofiban therapy immediately following successful EVT.
• Mechanistic Differentiation: Unlike previous trials focusing on fibrinolytics (alteplase/tenecteplase), this trial investigates a GP IIb/IIIa inhibitor, targeting the final common pathway of platelet aggregation to prevent re-occlusion and microvascular plugging.
• Broad Etiology Inclusion: Unlike some concurrent trials (e.g., ANGEL-DRUG) that exclude cardioembolic sources, ATTRACTION includes patients with cardioembolic stroke. This addresses a critical knowledge gap regarding the safety of antiplatelet therapy in cardioembolic contexts post-EVT.
• Rigorous Design: The study employs a large sample size, centralized adjudication of outcomes, and strict blinding to minimize bias, aiming to provide definitive evidence where previous small-scale or retrospective studies were inconclusive.

4. Results

• Status: As this document is a protocol preprint (posted February 26, 2026), no clinical results are available yet.
• Timeline:
  • First patient enrolled: April 9, 2024.
  • Enrollment completion: September 2025.
  • Follow-up completion: December 2025.
• The paper outlines the expected outcomes and the statistical framework for analyzing the data once the trial is completed.

5. Significance

• Clinical Practice: If successful, the trial could establish tirofiban as a standard adjunctive therapy for patients achieving successful recanalization, potentially converting "futile recanalizations" into functional recoveries.
• Policy and Guidelines: Results will inform national and international stroke guidelines regarding the use of antiplatelet agents in the acute post-thrombectomy phase.
• Research Direction: The inclusion of cardioembolic patients will clarify the safety profile of tirofiban in this high-risk subgroup, potentially resolving current controversies about hemorrhagic risks in cardioembolic stroke.
• Long-term Impact: The authors plan an extended follow-up analysis to assess long-term vascular events and sustained functional status, providing a comprehensive view of the therapy's value beyond the acute 90-day window.

Note: The document explicitly states that this is a preprint not yet certified by peer review and should not be used to guide clinical practice at this stage. The trial is registered under NCT06265051.