MRI-guided thrOmbolysis for Stroke bEyond Time Window by TNK (ROSE-TNK)

MRI-guided thrOmbolysis for Stroke bEyond Time Window by TNK (ROSE-TNK): a Prospective, Randomized, Blinded Assessment of Outcome and Open Label Multi-center Study

This is an open label multicentre trial, evaluating the utility of MRI-guided thrombolysis for stroke beyond time window by Tenecteplase (TNK-tPA). This exploratory study was to describe the feasibility and outcome of thrombolytic therapy with TNK-tPA in 4.5-24 hours after stroke guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Tenecteplase

Detailed Description

In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome at 90 days. This trial will enroll acute ischemic stroke patients within 4.5 to 24 hours of onset. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had a ischemic penumbra. Randomization will be 1:1 to TNK-tPA (experimental) or standard treatment (control), in compliance with guidelines for acute stroke. Clinical outcome was assessed by disability on the basis of the modified Rankin scale at 90 days follow-up, which will be performed by a blinded assessor.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110016
    • Department of Neurology, General Hospital of Northern Theater Command

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient age 18-80 years;
2. The time from onset to treatment: 4.5-24 hours;
3. Acute Ischemic stroke confirmed by MRI;
4. NIHSS score ：6-25, or NIHSS score≤ 5 but culprit vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on CTA/MRA;
5. Imaging requirements: (1) DWI infarct region: no more than 1/3 of middle cerebral artery territory or 1/2 of the anterior cerebral artery territory or 1/2 of the posterior cerebral artery territory; (2) DWI infarct volume <70 ml; (2) presence of DWI/Flair mismatch: DWI high signal and Flair visually normal;
6. the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1);
7. Signed informed consent

Exclusion Criteria:

1. Planned endovascular treatment;
2. Serious neurological deficits before onset ( mRS ≥ 2);
3. Obvious head injuries or strokes within 3 months;
4. Subarachnoid hemorrhage;
5. History of intracranial hemorrhage;
6. Intracranial tumor, arteriovenous malformation or aneurysm;
7. Intracranial or spinal cord surgery within 3 months;
8. Arterial puncture at a noncompressible site within the previous seven days;
9. Active internal hemorrhage;
10. coagulation abnormalities: platelet count of <100000/mm3 ；
11. Aortic arch dissection；
12. Heparin therapy within 24 hours;
13. Infective endocarditis；
14. Oral warfarin is being taken and INR>1.6 or APTT abnormal；
15. oral anticoagulation therapy；
16. Systolic pressure ≥185 mmHg or diastolic pressure ≥110 mmHg；
17. Blood glucose < 50 mg/dl (2.7mmol/L)；
18. Pregnancy;
19. Neurological deficit after epileptic seizures;
20. Major surgery within 1 month;
21. Gastrointestinal or urinary tract hemorrhage within the previous 30 days;
22. Myocardial infarction within 3 months;
23. allergy to study drugs;
24. Contradictory to MRI examination；
25. MRI image not qualified for evaluation；
26. Other serious illness；
27. Participating in other clinical trials within 3 months;
28. patients not suitable for this clinical studies considered by researcher.

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
Experimental: TNK-tPA; TNK-tPA (0.25mg/kg) given as a single bolus over 5-10 seconds immediately upon randomization.	Drug: Tenecteplase; The participants received TNK-tPA thrombolytic therapy; Other Names: TNK-tPA
No Intervention: Routine Therapy; Patients will be treated with standard of care in compliance with guidelines for acute stroke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of modified Rankin Scale (mRS) 0-1	the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of modified Rankin Scale (mRS) 0-2	the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome	90 Days
Distribution of the modified Rankin Scale (mRS)	the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome	90 Days
Changes in National Institute of Health stroke scale (NIHSS)	the minimum and maximum values of NIHSS are 42 and 0, respectively; higher NIHSS mean a worse outcome	24 hours and 1 week
vascular events	The incidence of stroke and other vascular events	90 Days
proportion of death	death due to any cause	14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of symptomatic intracranial hemorrhage (sICH)	sICH was defined as 4 or more increase in NIHSS caused by hemorrhage	48 hours
Proportion of intraparenchymal hemorrhage (PH1 and PH2)	Proportion of PH1 and PH2 within 48 hours after the treatment	48 hours
proportion of hemorrhagic transformation	Intracranial hemorrhage assessed by MRI/CT	7 Days
any bleeding events	proportion of any bleeding events	7 Days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Investigators: Study Director: Chen Hui-Sheng, Doctor, General Hospital of Shenyang Military Region

Publications and helpful links

General Publications

• Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, Ford I, Galinovic I, Gellissen S, Golsari A, Gregori J, Gunther M, Guibernau J, Hausler KG, Hennerici M, Kemmling A, Marstrand J, Modrau B, Neeb L, Perez de la Ossa N, Puig J, Ringleb P, Roy P, Scheel E, Schonewille W, Serena J, Sunaert S, Villringer K, Wouters A, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018 Aug 16;379(7):611-622. doi: 10.1056/NEJMoa1804355. Epub 2018 May 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): July 24, 2022
• Study Completion (Actual): July 24, 2022

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 31, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: stroke; TNK-tPA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: Y(2020)067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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