Unknown Time of Onset Stroke RePerfusIon Without Advanced Imaging (UTOPIA)

Intravenous Tenecteplase for Acute Ischemic Stroke With Unknown Time of Onset Under Non-Contrast CT Selection: A Multicenter, Prospective, Randomized, Open-label, Blinded Endpoint Trial

The benefit of intravenous tenecteplase for acute ischemic stroke with unknown time of onset, e.g. wake-up stroke, remains uncertain. This randomized study aims to assess the efficacy and safety of intravenous tenecteplase following non-contrast CT screening for acute ischemic stroke with unknown time of onset.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke; Tenecteplase
• Intervention / Treatment: Other: Standard medical treatment; Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)

Detailed Description

UTOPIA is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) trial that aims to assess the efficacy and safety of intravenous tenecteplase for acute ischemic stroke with unknown time of onset, selected by non-contrast CT. The primary outcome is excellent outcome, as defined by a score of 0 or 1 on modified Rankin Scale (mRS) at 90 days.

Participants randomized to the intervention group will receive intravenous tenecteplase at 0.25 mg/kg with a maximum dose of 25 mg and standard medical treatment, and those randomized to the control group will receive standard medical treatment only, without intravenous thrombolysis.

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dong Pan, MD, PhD; Phone Number: 86-156 2648 3251; Email: dongpan012@hotmail.com

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Dong Pan, MD, PhD; Phone Number: 86-156 2648 3251; Email: dongpan012@hotmail.com
      • Principal Investigator: Yuan Wu, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old.
2. Clinical diagnosis of acute ischemic stroke.
3. Unknown time of stroke onset (e.g., stroke symptom recognized on awakening) but last-known normal time >4.5 hours.
4. Time from stroke symptom recognition (e.g., awakening) to randomization within 3 hours.
5. National Institutes of Health Stroke Scale (NIHSS) score of 6-25 (both inclusive).
6. Pre-stroke modified Rankin Scale (mRS) score of 0-1.
7. Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria:

1. Intracranial hemorrhage confirmed by skull CT, or history of intracranial hemorrhage.
2. Rapid neurological improvement with NIHSS <6 at randomization.
3. Allergy to tenecteplase.
4. Use of vitamin K antagonist with INR >1.7, use of heparin or low molecular heparin in the past 24 hours, or use of direct oral anticoagulants in the past 48 hours.
5. Hypodensity on non-contrast CT >1/3 middle cerebral artery territory.
6. Severe traumatic brain injury or other major trauma in the past 3 months.
7. Intracranial neoplasm, arteriovenous malformation, or aneurysm (≥10mm).
8. Intracranial surgery, intraspinal surgery, or other major surgery in the past 3 months.
9. Gastrointestinal or urinary tract hemorrhage in the past 3 weeks.
10. Active internal bleeding.
11. Aortic dissection.
12. Infective endocarditis.
13. Platelet count <100×10^9/L.
14. Women who are pregnant or breastfeeding.
15. Blood glucose <50 or >400 mg/dL (<2.78 or >22.2 mmol/L).
16. Systolic blood presure >185 mmHg or diastolic blood presure >110 mmHg refractory to treatment.
17. Life expectancy <3 months.
18. Participating in other trials.
19. Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control group; Standard Medical Treatment	Other: Standard medical treatment; Standard medical treatment should adhere to clinical guidelines and usual care at site, including antiplatelet therapy, anticoagulant therapy, lipid-lowering therapy, antihypertensive drugs, etc., as determined by the local investigators.
Experimental: Tenecteplase group; Intravenous tenecteplase thrombolysis	Other: Standard medical treatment; Standard medical treatment should adhere to clinical guidelines and usual care at site, including antiplatelet therapy, anticoagulant therapy, lipid-lowering therapy, antihypertensive drugs, etc., as determined by the local investigators.; Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg); Tenecteplase is administered as a single intravenous bolus at a dose of 0.25 mg/kg, with a maximum of 25 mg, administered as soon as possible after the randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent outcome	The proportion of modified Rankin Scale (mRS) score of 0-1 at 90 days	90 (±14) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of disability	Ordinal shift analysis of the mRS with 5-6 merged at 90 days.	90 (±14) days
Functional independence	The proportion of mRS score of 0-2 at 90 days.	90 (±14) days
Early neurological improvement	The proportion of NIHSS 0-1 or ≥4 points reduction at 24 (±12) hours.	24 (±12) hours
Change in stroke severity	The change of NIHSS score from baseline to 7 days or at discharge (whichever comes first)	7 (±1) days or at discharge
Quality of life measured by EQ-5D-5L	EQ-5D-5L scale score at 90 days.	90 (±14) days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic intracranial hemorrhage	Incidence of symptomatic intracranial hemorrhage within 36 hours from randomization (Heidelberg criteria)	24 (±12) hours
Any intracranial hemorrhage	Incidence of any intracranial hemorrhage within 36 hours from randomization (Heidelberg classification)	24 (±12) hours
Extracranial bleeding	Incidence of moderate-to-severe extracranial bleeding (GUSTO criteria) within 36 hours from randomization	24 (±12) hours
Mortality	All cause death within 90 days.	90 days

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Guangxi Medical University
• Investigators: Principal Investigator: Yuan Wu, MD, PhD, First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: 2026-K0007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data supporting the findings of the study are available on reasonable request after approval of a proposal from the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No