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NCT Number: NCT06373042

Tirofiban for Successful Endovascular Stroke Thrombectomy

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Clinical inclusion criteria
  • Aged 18 years or older;
  • Acute ischemic stroke within 24 hours from last known well to randomization;
  • NIHSS score ≥6 and <30 points at baseline;
  • Written informed consent is obtained from patients and/or their legal representatives.
  • Imaging inclusion criteria
  • CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1 or M2 segment;
  • 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;
  • Treated with endovascular thrombectomy and achieved successful reperfusion (defined as eTICI grade 2b50 or higher).

Exclusion criteria

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

Treatment and study plan

Intraarterial and intravenous tirofiban

Drug

Intraarterial and intravenous tirofiban after endovascular thrombectomy

Other names: Tirofiban

Intraarterial and intravenous placebo

Drug

Intraarterial and intravenous placebo after endovascular thrombectomy

Other names: Placebo

Primary outcomes

  1. Functional independence

    Time frame: 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 outcomes

  1. Recanalization on follow-up CTA or MRA

    Time frame: within 48 hours post-randomization

    Measured with the arterial occlusive lesion (AOL) scale

  2. Early neurologic improvement

    Time frame: 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

  3. Level of disability

    Time frame: 90 days post-randomization

    Measured with the mRS

  4. Excellent outcome

    Time frame: 90 days post-randomization

    defined as mRS score of 0-1

  5. Independent ambulation

    Time frame: 90 days post-randomization

    defined as mRS score of 0-3

  6. Health-related quality of life

    Time frame: 90 days post-randomization

    European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score

  7. Long-term of disability level

    Time frame: 1 year post-randomization

    Measured with the mRS

  8. Health-related quality of life (long-term)

    Time frame: 1 year post-randomization

    European Quality Five-Dimension Five-Level (EQ-5D-5L) scale score

  9. Incidence of symptomatic intracranial hemorrhage (SICH)

    Time frame: within 48 hours post-randomization

    using Heidelberg criteria to assess SICH

  10. Radiologic intracranial hemorrhage rate

    Time frame: within 48 hours post-randomization

    using Heidelberg criteria to assess SICH

  11. Mortality

    Time frame: 90 days post-randomization

    Death from any cause

  12. Incidence of non-hemorrhagic serious adverse events

    Time frame: 90 days post-randomization

    such as pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc

Study contacts

Contact information is provided by the study sponsor or research team.

Thanh N. Nguyen, MD

CONTACT

[email protected]

Zhongming Qiu, MD

CONTACT

[email protected]

+8613236599269

Sponsors and collaborators

Lead sponsor

Zhongming Qiu

Other

Collaborators

  • Chongzhou People's Hospital
  • Mianyang Central Hospital
  • The Second Affiliated Hospital of Chongqing Medical University
  • The Second Hospital of Jiaozuo
  • Xihua People's Hospital
  • Xingguo People's Hospital

Registry information

Official study title

Efficacy and Safety of Tirofiban Versus Placebo After Successful Reperfusion With Endovascular Thrombectomy in Acute Ischemic Stroke Patients With Anterior Circulation Large Vessel Occlusion: a Multicenter, Double-Blind, Randomized Clinical Trial

Acronym: ADJUVANT-2

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Apr 18, 2024
Registry last updated
May 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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