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

Primary Purpose

Stroke

Status

Completed

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Tenecteplase

About this trial

This is an interventional treatment trial for Stroke focused on measuring TNK-tPA, stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient age 18-80 years;
The time from onset to treatment: 4.5-24 hours;
Acute Ischemic stroke confirmed by MRI;
NIHSS score ：6-25, or NIHSS score≤ 5 but culprit vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on CTA/MRA;
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;
the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1);
Signed informed consent

Exclusion Criteria:

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

Sites / Locations

Department of Neurology, General Hospital of Northern Theater Command

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

TNK-tPA

Routine Therapy

Arm Description

TNK-tPA (0.25mg/kg) given as a single bolus over 5-10 seconds immediately upon randomization.

Patients will be treated with standard of care in compliance with guidelines for acute stroke

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

vascular events

The incidence of stroke and other vascular events

proportion of death

death due to any cause

Full Information

NCT ID

NCT04752631

First Posted

February 9, 2021

Last Updated

July 31, 2022

Sponsor

General Hospital of Shenyang Military Region

1. Study Identification

Unique Protocol Identification Number

NCT04752631

Brief Title

MRI-guided thrOmbolysis for Stroke bEyond Time Window by TNK

Acronym

ROSE-TNK

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

March 9, 2021 (Actual)

Primary Completion Date

July 24, 2022 (Actual)

Study Completion Date

July 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

General Hospital of Shenyang Military Region

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke

Keywords

TNK-tPA, stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

The Outcomes will be performed by a blinded assessor.

Allocation

Randomized

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TNK-tPA

Arm Type

Experimental

Arm Description

TNK-tPA (0.25mg/kg) given as a single bolus over 5-10 seconds immediately upon randomization.

Arm Title

Routine Therapy

Arm Type

No Intervention

Arm Description

Patients will be treated with standard of care in compliance with guidelines for acute stroke

Intervention Type

Drug

Intervention Name(s)

Tenecteplase

Other Intervention Name(s)

TNK-tPA

Intervention Description

The participants received TNK-tPA thrombolytic therapy

Primary Outcome Measure Information:

Title

Proportion of modified Rankin Scale (mRS) 0-1

Description

the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome

Time Frame

90 Days

Secondary Outcome Measure Information:

Title

Proportion of modified Rankin Scale (mRS) 0-2

Description

the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome

Time Frame

90 Days

Title

Distribution of the modified Rankin Scale (mRS)

Description

the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome

Time Frame

90 Days

Title

Changes in National Institute of Health stroke scale (NIHSS)

Description

the minimum and maximum values of NIHSS are 42 and 0, respectively; higher NIHSS mean a worse outcome

Time Frame

24 hours and 1 week

Title

vascular events

Description

The incidence of stroke and other vascular events

Time Frame

90 Days

Title

proportion of death

Description

death due to any cause

Time Frame

14 days

Other Pre-specified Outcome Measures:

Title

Proportion of symptomatic intracranial hemorrhage (sICH)

Description

sICH was defined as 4 or more increase in NIHSS caused by hemorrhage

Time Frame

48 hours

Title

Proportion of intraparenchymal hemorrhage (PH1 and PH2)

Description

Proportion of PH1 and PH2 within 48 hours after the treatment

Time Frame

48 hours

Title

proportion of hemorrhagic transformation

Description

Intracranial hemorrhage assessed by MRI/CT

Time Frame

7 Days

Title

any bleeding events

Description

proportion of any bleeding events

Time Frame

7 Days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient age 18-80 years; The time from onset to treatment: 4.5-24 hours; Acute Ischemic stroke confirmed by MRI; NIHSS score ：6-25, or NIHSS score≤ 5 but culprit vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on CTA/MRA; 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; the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1); Signed informed consent Exclusion Criteria: Planned endovascular treatment; Serious neurological deficits before onset ( mRS ≥ 2); Obvious head injuries or strokes within 3 months; Subarachnoid hemorrhage; History of intracranial hemorrhage; Intracranial tumor, arteriovenous malformation or aneurysm; Intracranial or spinal cord surgery within 3 months; Arterial puncture at a noncompressible site within the previous seven days; Active internal hemorrhage; coagulation abnormalities: platelet count of <100000/mm3 ； Aortic arch dissection； Heparin therapy within 24 hours; Infective endocarditis； Oral warfarin is being taken and INR>1.6 or APTT abnormal； oral anticoagulation therapy； Systolic pressure ≥185 mmHg or diastolic pressure ≥110 mmHg； Blood glucose < 50 mg/dl (2.7mmol/L)； Pregnancy; Neurological deficit after epileptic seizures; Major surgery within 1 month; Gastrointestinal or urinary tract hemorrhage within the previous 30 days; Myocardial infarction within 3 months; allergy to study drugs; Contradictory to MRI examination； MRI image not qualified for evaluation； Other serious illness； Participating in other clinical trials within 3 months; patients not suitable for this clinical studies considered by researcher.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chen Hui-Sheng, Doctor

Organizational Affiliation

General Hospital of Shenyang Military Region

Official's Role

Study Director

Facility Information:

Facility Name

Department of Neurology, General Hospital of Northern Theater Command

City

Shenyang

ZIP/Postal Code

110016

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29766770

Citation

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.

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