Eptifibatide for Extended Window Ischemic Stroke After Thrombolysis (E-TWIST)

January 15, 2026 updated by: Zhongming Qiu, Xinqiao Hospital of Chongqing

Efficacy and Safety of Eptifibatide Therapy Following Intravenous Thrombolysis in Acute Ischemic Stroke Patients Within 4.5 to 24 Hours After Onset: A Multicenter, Randomized Controlled Trial

This is a multicenter, randomized, open-label, blinded-endpoint clinical trial designed to evaluate the efficacy and safety of early administration of eptifibatide following intravenous thrombolysis in patients with acute ischemic stroke who present 4.5 to 24 hours after symptom onset.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Several clinical trials (e.g., TRACE-3, EXPECTS, HOPE) have successfully extended the time window for intravenous thrombolysis (IVT) from the conventional 4.5 hours up to 24 hours after symptom onset by utilizing advanced imaging selection techniques. Consequently, the 2024 Chinese guidelines for reperfusion therapy recommend IVT for patients presenting 4.5 to 24 hours after onset, based on imaging selection criteria. However, clinical practice indicates that a considerable proportion of patients exhibit suboptimal recanalization outcomes or even experience early neurological deterioration (END) despite receiving standard IVT. Previous research, such as the ASSET-IT trial, has primarily focused on patients treated within 4.5 hours of onset. For the growing population of "extended-window" (4.5-24 hours) patients receiving IVT facilitated by advances in imaging, the optimal antiplatelet strategy following thrombolysis remains an area with no high-level evidence. Therefore, this study aims to evaluate the efficacy and safety of early administration of eptifibatide following standard IVT (with tenecteplase or alteplase) in patients with acute ischemic stroke who present 4.5 to 24 hours after symptom onset. Patients who have received standard IVT but exhibit early neurological deterioration, fluctuation, or lack of significant improvement within 1 hour post-thrombolysis will be randomized 1:1 to receive either eptifibatide (a single intravenous bolus followed by a 2-hour infusion) plus standard medical therapy or standard medical therapy alone. The primary efficacy outcome is the proportion of patients achieving an excellent functional outcome (modified Rankin Scale score of 0-1) at 90 days. The primary safety outcome is the incidence of symptomatic intracranial hemorrhage within 48 hours after randomization. A total of 786 participants are planned to be enrolled to detect a 10% absolute difference in the primary outcome with 80% power.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
786

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400000
        • Xinqiao Hospital and The Second Affiliated Hospital
        • Contact:
    • Hainan
      • Haikou, Hainan, China, 570100
        • The First Affiliated Hospital of Hainan Medical University
        • Contact:
    • Jiangxi
      • Ganzhou, Jiangxi, China, 341000
        • The First Affiliated Hospital of Gannan Medical University
        • Contact:
      • Ganzhou, Jiangxi, China, 341000
        • Ganzhou People's Hospital
        • Contact:
      • Ji’an, Jiangxi, China, 343000
        • The Affiliated Hospital of Jinggangshan University
        • Contact:
      • Nanchang, Jiangxi, China, 330006
        • The First Affiliated Hospital of Nanchang University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Acute ischemic stroke, with the time interval from last known well to hospital presentation being 4.5 to 24 hours.
  3. NIHSS score ≥ 4 before randomization; if large or medium vessel occlusion is present, an NIHSS score ≤ 10 is also required.

  4. Presence of any of the following conditions after completion of standard intravenous thrombolysis:

    1. No significant neurological improvement within 1 hour (defined as a change in NIHSS score ≤ 1 point from baseline).
    2. Early neurological deterioration within 1 hour of onset (defined as an increase in NIHSS score ≥ 2 points from baseline).
    3. Neurological fluctuation within 24 hours after symptom onset (defined as an increase in NIHSS score ≥ 2 points from the lowest value post-thrombolysis).
  5. Ability to receive the assigned study drug within 60 minutes after intravenous thrombolysis.
  6. Signed written informed consent obtained from the patient or their legal representative.

Exclusion Criteria:

  1. Intracranial hemorrhage confirmed by CT or MRI.
  2. Planned endovascular therapy.
  3. Presence of any definite cardioembolic source, including: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, endocarditis, intracardiac thrombus or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, spontaneous echo contrast in the left atrium, or ejection fraction < 30%.
  4. Pre-stroke modified Rankin Scale (mRS) score ≥ 2.
  5. Renal insufficiency (glomerular filtration rate < 30 ml/min or serum creatinine > 220 μmol/L [2.5 mg/dL]).
  6. Known hypercoagulable state.
  7. Platelet count < 100 × 10⁹/L.
  8. Pregnancy or lactation.
  9. Allergy to eptifibatide, other glycoprotein IIb/IIIa inhibitors, aspirin, or clopidogrel.
  10. History of non-atherosclerotic arteriopathy, including moyamoya disease, arterial dissection, or fibromuscular dysplasia.
  11. Pre-existing neurological or psychiatric disease that would preclude accurate neurological assessment.
  12. History of bleeding diathesis, severe cardiac disease, liver disease, or sepsis.
  13. Brain tumor with mass effect on imaging (except for small meningiomas).
  14. Evidence of intracranial arteriovenous malformation or aneurysm with diameter > 5 mm on CT or MR angiography.
  15. Current participation in another clinical trial.
  16. Any terminal illness with life expectancy < 6 months.
  17. Anticipated inability to complete follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Eptifibatide (Integrilin)
Participants randomized to this arm will receive intravenous eptifibatide (135 μg/kg bolus, followed by 0.75 μg/kg/min infusion for 2 hours) initiated within 60 minutes after completion of standard intravenous thrombolysis (either alteplase or tenecteplase). Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.
Drug: Eptifibatide (Integrilin)
Participants will receive intravenous eptifibatide (135 μg/kg bolus, followed by 0.75 μg/kg/min infusion for 2 hours) initiated within 60 minutes after completion of standard intravenous thrombolysis (either alteplase or tenecteplase). Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.
Active Comparator: Standard Medical Therapy
Participants randomized to this arm will not receive intravenous eptifibatide after completion of standard intravenous thrombolysis. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.
Drug: Standard Medical Therapy
Participants will not receive intravenous eptifibatide after completion of standard intravenous thrombolysis. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Excellent functional outcome
Time Frame: 90 days post-randomization
modified Rankin scale score of 0 to 1. 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ordinal degree of disability
Time Frame: 90 days post-randomization
Ordinal degree of disability on the modified Rankin scale score at 90 days (shift analysis)
90 days post-randomization
Functionally independent
Time Frame: 90 days post-randomization
modified Rankin scale score of 0 to 2
90 days post-randomization
Health-related quality of life
Time Frame: 90 days post-randomization
assessed with the European Quality Five Dimensions Five Level scale
90 days post-randomization
Mortality
Time Frame: 90 days post-randomization
The proportion of participants who die from any cause within 90 days after randomization in the study
90 days post-randomization
Conversion to Endovascular Therapy
Time Frame: 24 hours post-randomization
Proportion of patients who converted to endovascular therapy
24 hours post-randomization
Change in NIHSS Score at 48 (±12) Hours
Time Frame: 48 (±12) hours post-randomization
Change in NIHSS score from pre-randomization to 48 (±12) hours
48 (±12) hours post-randomization
Change in NIHSS Score at Discharge or Day 6 (±1)
Time Frame: Day 6 (±1) or discharge post-randomization, whichever came first
Change in NIHSS score from pre-randomization to discharge or day 6 (±1)
Day 6 (±1) or discharge post-randomization, whichever came first
Symptomatic intracranial hemorrhage
Time Frame: 48 (±12) hours post-randomization
defined as per the Heidelberg bleeding classification
48 (±12) hours post-randomization
Incidence of major extracranial bleeding within 48 (±12) hours
Time Frame: 48 (±12) hours post-randomization
GUSTO criteria: moderate and severe bleeding
48 (±12) hours post-randomization
Incidence of non-hemorrhagic serious adverse events
Time Frame: Within 90 days post-randomization
Including but not limited to cerebral herniation, pneumonia, respiratory failure, circulatory failure, stress ulcer, secondary epilepsy, urinary tract infection, sepsis, renal failure, acute coronary syndrome, venous thrombosis, and psychiatric symptoms
Within 90 days post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xinqiao Hospital of Chongqing

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The First Affiliated Hospital of Nanchang University
The First Affiliated Hospital of Hainan Medical College

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daojun Hong, MD, The First Affiliated Hospital of Nanchang University
  • Principal Investigator: Zhongming Qiu, MD, Xinqiao Hospital of the Army Medical University
  • Principal Investigator: Zhenqiang Zhao, MD, The First Affiliated Hospital of Hainan Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2026

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2026

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E-TWIST

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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