Ticagrelor With Aspirin Dual Antiplatelet Therapy Combined With Intravenous Thrombolysis for Ischemic Stroke

Phase 3

Recruiting

• Conditions: Ischemic Stroke, Acute
• Interventions: Drug: Early Dual Antiplatelet Therapy; Drug: Placebo

• Registration Number: NCT06316570
• Lead Sponsor: Beijing Tiantan Hospital

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.

Study Timeline

• Study First Submitted: 2024-03-12
• Study First Submitted QC: 2024-03-12
• Study First Posted: 2024-03-18
• Study Start: 2024-04-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-15
• Primary Completion: 2025-12-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1380

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dual Antiplatelet Therapy	Early Dual Antiplatelet Therapy	This group will receive early dual antiplatelet therapy (Ticagrelor with Aspirin) combined with intravenous thrombolysis within 6 hours of the onset.
Placebo	Placebo	This group will receive placebo treatment (with same form and dosage) combined with intravenous thrombolysis within 6 hours of the onset.

Primary Outcome Measures

Name	Time	Method
Excellent functional outcome	90 days	Modified Rankin Scale (mRS) score of 0-1 points; The mRS score ranges from 0 to 6, with higher scores indicating worse functional outcome.

Secondary Outcome Measures

Name	Time	Method
mRS score of 0-2 points	90 days	The mRS score ranges from 0 to 6, with higher scores indicating worse functional outcome.
Distribution of mRS score	90 days	The distribution of mRS score of 0 to 6 points; The mRS score ranges from 0 to 6, with higher scores indicating worse functional outcome.
Neurologic improvement	7 days	NIHSS score decreasing by 4 points or more than the value at baseline; The National Institutes of Health Stroke Scale (NIHSS) score ranges from 0 to 42, with higher scores indicating more severe neurological deficit.
Quality of life (EQ-5D scale)	90 days	The European Quality of Life 5-Dimension（EQ-5D）questionnaire for measuring generic health status. The 5-level EQ-5D version (EQ-5D-5L) comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The sum score on each of the five dimensions ranges from 5 (all domains have level 1) to 25 (all domains have level 5), with higher scores indicating worse health-related quality of life.
Activity of daily living (Barthel index ≥95 points)	90 days	The Barthel index score ranges from 0 to 100, with higher scores indicating greater independence.
Recurrent ischemic stroke	90 days
Symptomatic intracranial hemorrhage (ECASS-III)	7 days
Parenchymal hematoma type 2 (SIST-MOST)	7 days
Bleeding events (GUSTO)	90 days
Adverse events	90 days
Severe adverse events	90 days

Trial Locations

Locations (66)

Liuyang Jili Hospital; 🇨🇳 Changsha, Hunan, China

Northern Jiangsu People's Hospital; 🇨🇳 Yangzhou, Jiangsu, China

Yuci District People's Hospital; 🇨🇳 Jinzhong, Shanxi, China

Beijing Haidian Hospital; 🇨🇳 Beijing, Beijing, China

China Aerospace Science and Industry Corporation 731 Hospital; 🇨🇳 Beijing, Beijing, China

Chongqing Sanbo Changan Hospital; 🇨🇳 Chongqing, Chongqing, China

The First Affiliated Hospital of Guangdong Pharmaceutical University; 🇨🇳 Guangzhou, Guangdong, China

Heyuan People's Hospital; 🇨🇳 Heyuan, Guangdong, China

Huazhou People's Hospital; 🇨🇳 Maoming, Guangdong, China

Meizhou Hospital of Traditional Chinese Medicine; 🇨🇳 Meizhou, Guangdong, China

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