Clinical trial NCT06265051: Tirofiban After Successful MT Recanalization in AIS
Official title: Safety and Efficacy of Adjunct Tirofiban Treatment After Successful Mechanical Thrombectomy Recanalization in Acute Anterior Circulation Ischemic Stroke- A Multicenter, Prospective, Double-blind, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Ischemic Stroke
Vessel Occlusion
Keywords: mechanical thrombectomy
acute ischemic stroke
successful recanalization
tirofiban
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Wuhan Central Hospital
name: Zhongnan Hospital
name: Renmin Hospital of Wuhan University
name: Second Affiliated Hospital of Soochow University
name: The First Affiliated Hospital of Zhengzhou University
name: Wuhan Hospital of Traditional Chinese Medicine
name: The Central Hospital of Enshi Tujia And Miao Autonomous Prefecture
name: Huangshi Central Hospital, China
name: The First Affiliated Hospital of Yangtze University
name: The Fifth Hospital of Wuhan
name: Wuhan Puren Hospital
name: Xiangyang No.1 People's Hospital
name: Xianning Central Hospital
name: Hanyang University
name: Wuhan Third Hospital
name: Yichang Central People's Hospital
name: Affiliated Hospital of Chengde Medical University
name: Beijing Tiantan Hospital
name: Nanyang Central Hospital
name: Jingzhou Central Hospital
name: Taihe Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2024-02-20
Enrollment: 1360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute ischemic stroke with large vessel occlusion is a frequently occurring life-threatening condition. Although endovascular treatment can effectively open occluded vessels, the successful reperfusion rate exceeds 80%, but the rate of good prognosis is less than 50%. The current clinical focus is on how to improve futile recanalization. Tirofiban is widely used in the treatment of stroke, as it can effectively prevent vascular reocclusion and improve microcirculation perfusion. It has the potential to improve futile recanalization, but there is a lack of high-level evidence-based medical support. This multicenter, prospective, double-blind, randomized controlled trial was conducted to assess the effectiveness and safety of sequential tirofiban therapy following successful mechanical thrombectomy within 24 hours of onset.

Detailed description: Endovascular treatment is the primary approach for significantly improving the clinical prognosis of patients with acute large vessel occlusion, and it has been consistently recommended by both domestic and foreign guidelines. Successful vascular recanalization and restoration of ischemic tissue reperfusion are crucial for the favorable prognosis of patients with large vessel occlusion. However, the rate of successful reperfusion after endovascular treatment exceeds 80%, but the rate of favorable outcomes at 90 days follow-up is less than 50%. The reasons for ineffective recanalization include reperfusion injury, arterial reocclusion, hemorrhagic transformation, and microvascular reperfusion insufficiency. Although vascular recanalization can be visualized using DSA, not all microvascular beds can be effectively perfused, and persistent microocclusion of the capillary bed in ischemic tissue will also result in a poor prognosis. Currently, drug intervention is not commonly utilized to achieve successful recanalization after mechanical thrombectomy in clinical practice. Additionally, there is a lack of effective methods to improve ineffective recanalization.

Tirofiban is widely used in the treatment of stroke, as it can effectively prevent vascular reocclusion and improve microcirculation perfusion. It has the potential to improve futile recanalization, but there is a lack of high-level evidence-based medical support.

This is a prospective, randomized, multicenter, double-blind clinical trial. In 52 centers in China, 1360 patients with the following situations will be enrolled: achieved successful recanalization after mechanical thrombectomy (mTICI 2b/3) within 24h of stroke onset.

Patients will be randomly assigned into 2 groups according to the ratio of 1:1:

1. experimental group received a bolus of tirofiban at a dosage of 5μg/kg (with a maximum dose not exceeding 0.5mg) through the catheter artery, followed by a continuous intravenous infusion at a rate of 0.1μg/(kg·min) for 24 hours.
2. The control group was given a placebo in the same manner. Face to face interviews will be made on baseline, 24 hours after randomization, 48 hours after randomization, day 7 after randomization or discharge day. Day 90 after randomization will be interviewed by phone or face to face.

The main measure of effectiveness was the rate of mRS 0-2 after 90 days, and the primary focus on safety was the rate of symptomatic intracranial hemorrhage within 48 hours. This study aims to clarify the role of tirofiban in enhancing unsuccessful recanalization after thrombectomy, which holds significant clinical value in improving the prognosis of patients following thrombectomy.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old;
2. NIHSS score: 6-30;
3. Symptom onset to random time of 24h, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
4. mRS 0-1 before the stroke;
5. Subject or legal representative can sign an informed consent form;
6. Clinical symptoms caused by acute occlusion of the following sites confirmed by CTA or MRA: intracranial segment of ICA, M1 segment of middle cerebral artery, M2 trunk of middle cerebral artery;
7. ASPECTS≥6 on NCCT or DWI;
8. After the end of mechanical thrombectomy, the mTICI was stable at 2b/3, and there was no secondary embolism in other non-offending vessels, or the diagnostic angiography before mechanical thrombectomy showed that the occluded vessels improved to mTICI 2b/3, and no mechanical thrombectomy was planned.

Exclusion Criteria:

1. Intra-arterial thrombolysis;
2. Tirofiban was used within 24 hours before endovascular treatment
3. Women who are known to be pregnant or lactating, or have a positive pregnancy test before randomization;
4. Allergy to tirofiban, radiocontrast agent or Nitinol materials;
5. Any active bleeding within 30 days before stroke or recent bleeding (gastrointestinal, urinary, etc.);
6. parenchymal organ surgery or biopsy within 14 days before stroke;
7. History of heparin-induced thrombocytopenia;
8. Platelet count \< 100\*10\^9/L;
9. Being on hemodialysis or peritoneal dialysis; Known severe renal insufficiency (glomerular filtration rate \&lt; 30ml/min or serum creatinine \&gt; 220μmol/L).
10. Subjects requiring hemodialysis or peritoneal dialysis or who have contraindications to angiography for any reason;
11. The expected survival time is less than half a year (such as malignant tumors, serious heart and lung diseases, etc.);
12. Have participated in other interventional clinical studies that may have an impact on the outcome assessment;
13. Other circumstances that the investigator considers inappropriate for participation in the study or that may pose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorder).
14. The midline shift of the brain or cerebral hernia, ventricular mass effect;
15. Acute intracranial hemorrhage on CT or MRI;
16. New bilateral acute stroke or intracranial multi-drainage large vessel occlusion;
17. Simple extracranial occlusion of the internal carotid artery.

Primary outcomes:
measure: Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
timeFrame: 90 days after randomization
measure: Number of participants with symptomatic intracranial hemorrhage
timeFrame: within 48 hours of randomization
Secondary outcomes:
measure: Modified ranking scale (mRS)
timeFrame: 90 days after randomization
measure: Proportion of patients non-disabled (mRS score 0 to 1) or return to pre-morbid mRS score at 90 days (for patients with mRS > 1)
timeFrame: 90 days after randomization
measure: Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)
timeFrame: 90 days after randomization
measure: Number of participants with improvement of neurological function
timeFrame: 36 hours (24-48 hours) after randomization
measure: Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L)
timeFrame: 90 days after randomization
measure: All-cause mortality
timeFrame: 90 days after randomization
measure: Proportion of intracranial hemorrhage of any type
timeFrame: within 48 hours of randomization
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Xiang Luo
role: PRINCIPAL_INVESTIGATOR
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