Tirofiban for Successful Endovascular Stroke Thrombectomy

NCT06373042 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ADJUVANT-2
• Study Type: interventional
• Target: 712
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Stroke, Acute Ischemic

Outcome Measures

Primary Outcomes (1)

• Functional independence

  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)

  90 days post-randomization

Secondary Outcomes (12)

• Recanalization on follow-up CTA or MRA

  within 48 hours post-randomization

• Early neurologic improvement

  within 48 hours post-randomization

• Level of disability

  90 days post-randomization

• Excellent outcome

  90 days post-randomization

• Independent ambulation

  90 days post-randomization

Study Arms (2)

Tirofiban

EXPERIMENTAL

Intraarterial and intravenous tirofiban

Drug: Intraarterial and intravenous tirofiban

Placebo

PLACEBO COMPARATOR

Intraarterial and intravenous placebo

Drug: Intraarterial and intravenous placebo

Interventions

Intraarterial and intravenous tirofiban DRUG

Intraarterial and intravenous tirofiban after endovascular thrombectomy

Also known as: Tirofiban

Tirofiban

Intraarterial and intravenous placebo DRUG

Intraarterial and intravenous placebo after endovascular thrombectomy

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhongming Qiu: lead
• Mianyang Central Hospital: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• The Second Hospital of Jiaozuo: collaborator
• Chongzhou People's Hospital: collaborator
• Xihua People's Hospital: collaborator
• Xingguo People's Hospital: collaborator

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Infusions, Intra-Arterial; Tirofiban

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Infusions, Parenteral; Drug Administration Routes; Drug Therapy; Therapeutics; Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Zhongming Qiu, MD

  The 903rd Hospital of PLA, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhongming Qiu, MD

CONTACT

+8613236599269; qiuzhongmingdoctor@163.com

Thanh N. Nguyen, MD

CONTACT

thanh.nguyen@bmc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Related papers published 3 months later, the IPD will be shared.
• Access Criteria: qiuzhongmingdoctor@163.com