Clinical trial NCT06316570: Ticagrelor With Aspirin Dual Antiplatelet Therapy Combined With Intravenous Thrombolysis for Ischemic Stroke
Official title: Efficacy and Safety of Ticagrelor With Aspirin Dual Antiplatelet Therapy Combined With Intravenous Thrombolysis in Patients With Ischemic Stroke (TAPIS): a Multicenter, Randomized, Double-blind, Placebo-parallel Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke, Acute
Keywords: Ischemic Stroke
Antiplatelet Therapy
Intravenous Thrombolysis
Randomized Controlled Trial
Double Blind Study
Multicenter Study
Clinical Trial
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-03-18
Enrollment: 1380
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Early antiplatelet therapy is promising for further improvement of functional prognosis on the basis of intravenous thrombolytic therapy. The primary purpose of this multicenter, randomized, double-blind, placebo-parallel controlled trial is to evaluate the efficacy and safety of the early dual antiplatelet therapy (within 6 hours of onset ) of ticagrelor with aspirin combined with intravenous thrombolysis in improving good functional outcome (mRS score 0-1) at 90 days inpatients with ischemic stroke.

Detailed description: Theoretically, early administration of antiplatelet therapy is expected to counteract platelet aggregation during intravenous thrombolysis, improving the efficacy of intravenous thrombolysis as well as the functional prognosis. According to current evidence, mainstream guidelines clearly state that the administration of intravenous aspirin (or other antiplatelet agents) within 24 hours of Recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy is not recommended as an adjunctive treatment of intravenous thrombolysis therapy, despite the fact that rt-PA thrombolytic therapy is still acceptable for patients who have received antiplatelet therapy before the onset of stroke. Evidence from high-quality clinical trials for the routine use of oral antiplatelet drugs before and within 24 hours of intravenous thrombolysis in acute ischemic stroke (AIS) patients is quite limited. Meanwhile, trials including INSPIRES and CHANCE 2 have demonstrated that early initiation of dual antiplatelet therapy could significantly reduce the risk of recurrence and thus improve the functional prognosis without significantly increasing the risk of bleeding, providing a promising treatment for early oral antiplatelet therapy in patients undergoing intravenous thrombolysis.

This trial is a multicenter, randomized, double-blind, placebo-parallel controlled designed clinical trial. A total of 1380 patients (aged 18-80 years) who have a new diagnosed ischemic stroke (within 6 hours of onset), a NIHSS score of 4-10 points, and have received/are planned to receive intravenous thrombolysis therapy with will be enrolled from 50 centers in China. Patients will be randomly assigned into intervention (dual antiplatelet therapy of Ticagrelor and Aspirin) and control group (placebo) by the ratio of 1:1. Face to face or distance (via video or telephone) interviews will be made at baseline, 7 ± 1 days, 30 ± 3 days, 60 ± 5 days and 90 ± 7 days after randomization.

Primary outcome is defined as good functional outcomes (mRS score of 0-1 points) at 90 days. Secondary outcomes include neurologic improvement，quality of life ( quality-of-life EuroQol-5 Dimensions scale)，activity of daily living (Barthel index)，recurrent ischemic stroke. Safety outcomes, relating to antiplatelet and intravenous thrombolysis therapy (i.e., symptomatic intracranial hemorrhage, parenchymal hematoma type 2, bleeding events) will also be investigated.

The Chi-square test was used to compare the proportion difference of good functional outcomes between two groups after 90 days of treatment, and the 95% confidence interval (CI) was calculated by using the Newcombe method. The generalized linear regression model was used to calculate the relative risk (RR) and its 95%CI. For survival outcomes, hazard ratio (HR) and 95% CI were calculated using the Cox proportional risk model.

Eligibility criteria: Inclusion Criteria:

* 1. 18-80 years old;

  2. Clinical diagnosis of acute ischemic stroke;

  3. Time from onset to treatment ≤6.0 hours;

  4. Having received or planning to receive intravenous thrombolytic therapy;

  5. NIHSS score of 4-10 points, and at least one of the 5th (upper limb exercise) or 6 th (lower limb exercise) scale is ≥1 point;

  6. Signed informed consent.

Exclusion Criteria:

* 1. Planning to receive endovascular therapy;

  2. mRS scores ≥2 points before the onset;

  3. Receiving any antiplatelet therapy after the onset;

  4. Bleeding or other pathological brain disorders, such as vascular malformations, tumors, abscesses, or other common non-ischemic brain diseases (such as multiple sclerosis), identified by CT/MRI;

  5. Pre-existing clotting disorders, systemic bleeding, thrombocytopenia, or neutropenia;

  6. Pre-existing atrial fibrillation or anticoagulant therapy (warfarin, heparin, thrombin inhibitors or factor Xa inhibitors);

  7. Hepatic or renal insufficiency (hepatic insufficiency refers to the alanine transaminase (ALT) value \> 2 times the upper limit of normal value or aspartate aminotransferase (AST) times \> 2 times the upper limit of normal value; renal insufficiency refers to creatinine values \> 2 times the upper limit of normal value);

  8. Allergic to Ticagrelor or Aspirin or thier components and excipients;

  9. Women who are pregnant or breastfeeding, or those with negative pregnancy test records while refusing to use effective contraceptives;

  10. Having participated investigational drugs or device tests within 30 days;

  11. Being considered inappropriate to participate by researchers.

Primary outcomes:
measure: Excellent functional outcome
timeFrame: 90 days
Secondary outcomes:
measure: mRS score of 0-2 points
timeFrame: 90 days
measure: Distribution of mRS score
timeFrame: 90 days
measure: Neurologic improvement
timeFrame: 7 days
measure: Quality of life (EQ-5D scale)
timeFrame: 90 days
measure: Activity of daily living (Barthel index ≥95 points)
timeFrame: 90 days
measure: Recurrent ischemic stroke
timeFrame: 90 days
measure: Symptomatic intracranial hemorrhage (ECASS-III)
timeFrame: 36 hours
measure: Symptomatic intracranial hemorrhage (ECASS-III)
timeFrame: 7 days
measure: Parenchymal hematoma type 2 (SIST-MOST)
timeFrame: 36 hours
measure: Parenchymal hematoma type 2 (SIST-MOST)
timeFrame: 7 days
measure: Bleeding events (GUSTO)
timeFrame: 90 days
measure: Adverse events
timeFrame: 90 days
measure: Severe adverse events
timeFrame: 90 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Haidian Hospital
state: Beijing
city: Beijing
country: China
facility: China Aerospace Science and Industry Corporation 731 Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Sanbo Changan Hospital
state: Chongqing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Heyuan
country: China
facility: Heyuan People's Hospital
state: Guangdong
city: Maoming
country: China
facility: Huazhou People's Hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou Hospital of Traditional Chinese Medicine
state: Guangdong
city: Zhanjiang
country: China
facility: Wuchuan People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Yulin
country: China
facility: Yulin First People's Hospital
state: Guangxi
city: Xingtai
country: China
facility: Qinghe County People's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Affiliated First Hospital
state: Heilongjiang
city: Harbin
country: China
facility: Wuchang Hospital of Traditional Chinese Medicine
state: Heilongjiang
city: Anyang
country: China
facility: Puyang Anyang District Hospital
state: Henan
city: Jiyuan
country: China
facility: Jiyuan Hospital of Traditional Chinese Medicine
state: Henan
city: Kaifeng
country: China
facility: Kaifeng Central Hospital
state: Henan
city: Kaifeng
country: China
facility: Lankao County Central Hospital
state: Henan
city: Kaifeng
country: China
facility: Lankao County Traditional Chinese Medicine Hospital
state: Henan
city: Kaifeng
country: China
facility: Qixian People's Hospital
state: Henan
city: Kaifeng
country: China
facility: Qixian Traditional Chinese Medicine Hospital
state: Henan
city: Kaifeng
country: China
facility: The First People's Hospital of Xiangfu District, Kaifeng City
state: Henan
city: Luohe
country: China
facility: Luohe Third People's Hospital
state: Henan
city: Puyang
country: China
facility: Nanle Zhongxing Hospital
state: Henan
city: Shangqiu
country: China
facility: Shangqiu First People's Hospital
state: Henan
city: Shangqiu
country: China
facility: Shangqiu Third People's Hospital
state: Henan
city: Shangqiu
country: China
facility: Suixian Hospital of Traditional Chinese Medicine
state: Henan
city: Shangqiu
country: China
facility: Suixian People's Hospital
state: Henan
city: Shangqiu
country: China
facility: Xiayi People's Hospital
state: Henan
city: Shangqiu
country: China
facility: Yongcheng People's Hospital
state: Henan
city: Weishi
country: China
facility: Weishi County Central Hospital
state: Henan
city: Weishi
country: China
facility: Weishi County Traditional Chinese Medicine Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Jingmen
country: China
facility: Jingmen Hospital of Traditional Chinese Medicine
state: Hubei
city: Wuhan
country: China
facility: Wuhan Huangpi District People's Hospital
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Liuyang Jili Hospital
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou First People's Hospital
state: Hunan
city: Chenzhou
country: China
facility: The Fourth People's Hospital of Chenzhou City
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
state: Inner Mongolia
city: Hinggan
country: China
facility: Tuquan People's Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia Hangtian Hospital
state: Inner Mongolia
city: Hulun Buir
country: China
facility: Zalantun People's Hospital
state: Inner Mongolia
city: Hulun Buir
country: China
facility: Zalantun Zhongmeng Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huaian Second People's Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Anshan
country: China
facility: Anshan Changda Hospital
state: Liaoning
city: Benxi
country: China
facility: Benxi Central Hospital
state: Liaoning
city: Dalian
country: China
facility: Dalian Lushunkou District People's Hospital
state: Liaoning
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Dalian
country: China
facility: Xinhua Hospital Affiliated to Dalian University
state: Liaoning
city: Dandong
country: China
facility: Dandong Central Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shenyang First People's Hospital
state: Liaoning
city: Henan
country: China
facility: Lingbao First People's Hospital
state: Sanmenxia
city: Liaocheng
country: China
facility: Guanxian People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linshu People's Hospital
state: Shandong
city: Penglai
country: China
facility: Yantai Penglai Traditional Chinese Medicine Hospital
state: Shandong
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
state: Shandong
city: Weihai
country: China
facility: Weihai Wendeng District People's Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Municipal Hospital
state: Shandong
city: Jincheng
country: China
facility: Jincheng People's Hospital
state: Shanxi
city: Jinzhong
country: China
facility: Yuci District People's Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Xiqing Hospital
state: Tianjin
city: Shihezi
country: China
facility: The First Affiliated Hospital of Shihezi University Medical College
state: Xinjiang
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yilong Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: