Tirofiban for Successful Endovascular Stroke Thrombectomy

Phase 2

Not yet recruiting

• Conditions: Stroke, Acute Ischemic
• Interventions: Drug: Intraarterial and intravenous tirofiban; Drug: Intraarterial and intravenous placebo

• Registration Number: NCT06373042
• Lead Sponsor: Zhongming Qiu

Brief Summary

Up to 50% of acute ischemic stroke patients with large vessel occlusion failed to achieve functional independence even after successful reperfusion therapy, a phenomenon that is referred to as "futile recanalization". The mechanism of futile recanalization is complex, and some studies have shown that it may be related to factors such as tissue no reflow, reocclusion, poor status of collateral circulation, hemorrhagic transformation, impaired cerebrovascular autonomic regulation, and low perfusion volume. Several studies suggested that maximizing the improvement of cerebral reperfusion is still the primary goal of acute large vessel occlusive stroke. Structural and functional alterations in the microvascular system may be a major obstacle to reperfusion. In animal models of cerebral ischemia, downstream microvascular thrombosis may occur in the early stage of cerebral ischemia and before vascular recanalization, which is the main factor leading to incomplete reperfusion and affecting the efficacy of endovascular thrombectomy.

Mechanical thrombectomy mainly addressed the occluded large arteries, and does not consider the distal arteries. However, the recanalization of occluded large arteries does not necessarily translate into successful reperfusion of the ischemic tissue supplied by the distal capillaries. Even with complete recanalization, impaired microcirculatory reperfusion may lead to poor clinical outcomes. Therefore, we speculate that at the end of endovascular thrombectomy, microthrombi remain present in the microcirculation of brain tissue in patients with complete or near-complete cerebral angiography, and that microthrombi is more likely to be dissolved than thrombus more proximal to the heart. Therefore, intra-arterial administration of pharmaceutical, such as tirofiban, may be the only possible option to ensure complete reperfusion of ischemic tissue. Tirofiban is a platelet glycoprotein IIb/IIIa receptor antagonist, which has been widely used in acute coronary syndrome, and its role in acute ischemic stroke has attracted more and more attention from stroke experts. Previous studies have suggested that tirofiban can further increase the incidence of successful recanalization, while reducing the reocclusion rate.

Whether early administration of intraarterial and intravenous tirofiban can further improve the clinical outcomes of patients with large vessel occlusive stroke after successful mechanical thrombectomy remains unclear.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-15
• Study First Submitted QC: 2024-04-15
• Study First Posted: 2024-04-18
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-13
• Last Update Posted: 2024-05-16
• Study Start: 2024-07-31
• Primary Completion: 2026-07-31
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 712

Inclusion Criteria

• Clinical inclusion criteria

  1. Aged 18 years or older;
  2. Acute ischemic stroke within 24 hours from last known well to randomization;
  3. NIHSS score ≥6 and <30 points at baseline;
  4. Written informed consent is obtained from patients and/or their legal representatives.

• Imaging inclusion criteria

  1. CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1 or M2 segment;
  2. For patients within 6 hours from last known well to randomization, ASPECTS 3-10 or infarct volume ≤100ml; 6-24 hours, ASPECTS 6-10 or infarct volume ≤70ml or DWI-FLAIR mismatch;
  3. Treated with endovascular thrombectomy and achieved successful reperfusion (defined as eTICI grade 2b50 or higher).

Exclusion Criteria

1. Cardiogenic embolism;
2. Patient receive tirofiban for angioplasty/stenting prior to randomization;
3. Intracranial hemorrhage confirmed by flat panel CT on angiography machine prior to randomization;
4. Patients who are on prior anticoagulant therapy, e.g. for deep venous thrombosis or pulmonary embolism or mechanical heart valve;
5. Routine blood test platelet count less than 100×10⁹/L;
6. Renal insufficiency, glomerular filtration rate < 60 mL/min;
7. Pregnant or lactating women;
8. Allergy to tirofiban, contrast agent, nickel, titanium or its alloys;
9. History of neurological or psychiatric illness that precludes the assessment of neurological function;
10. History of bleeding disorder, severe heart, liver or kidney disease, or sepsis;
11. Any terminal illness with life expectancy less than 6 months;
12. Participating in other treatment clinical trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirofiban	Intraarterial and intravenous tirofiban	Intraarterial and intravenous tirofiban
Placebo	Intraarterial and intravenous placebo	Intraarterial and intravenous placebo

Primary Outcome Measures

Name	Time	Method
Functional independence	90 days post-randomization	modified Rankin scale score of 0 to 2. (The modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)

Secondary Outcome Measures

Name	Time	Method
Mortality	90 days post-randomization	Death from any cause
Level of disability	90 days post-randomization	Measured with the mRS
Excellent outcome	90 days post-randomization	defined as mRS score of 0-1
Independent ambulation	90 days post-randomization	defined as mRS score of 0-3
Radiologic intracranial hemorrhage rate	within 48 hours post-randomization	using Heidelberg criteria to assess SICH
Long-term of disability level	1 year post-randomization	Measured with the mRS
Incidence of non-hemorrhagic serious adverse events	90 days post-randomization	such as pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc
Recanalization on follow-up CTA or MRA	within 48 hours post-randomization	Measured with the arterial occlusive lesion (AOL) scale
Health-related quality of life	90 days post-randomization	European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score
Health-related quality of life (long-term)	1 year post-randomization	European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score
Early neurologic improvement	within 48 hours post-randomization	defined as NIHSS score at 48 hours after randomization is reduced by 8 or more compared to NIHSS score at randomization; or the NIHSS at 48 hours after randomization is 0 to 1
Incidence of symptomatic intracranial hemorrhage (SICH)	within 48 hours post-randomization	using Heidelberg criteria to assess SICH