Clinical trial NCT04752631: MRI-guided thrOmbolysis for Stroke bEyond Time Window by 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stroke
Keywords: TNK-tPA
stroke
Lead sponsor: General Hospital of Shenyang Military Region
Sponsor class: OTHER
First posted: 2021-02-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of modified Rankin Scale (mRS) 0-1
timeFrame: 90 Days
Secondary outcomes:
measure: Proportion of modified Rankin Scale (mRS) 0-2
timeFrame: 90 Days
measure: Distribution of the modified Rankin Scale (mRS)
timeFrame: 90 Days
measure: Changes in National Institute of Health stroke scale (NIHSS)
timeFrame: 24 hours and 1 week
measure: vascular events
timeFrame: 90 Days
measure: proportion of death
timeFrame: 14 days
Other outcomes:
measure: Proportion of symptomatic intracranial hemorrhage (sICH)
timeFrame: 48 hours
measure: Proportion of intraparenchymal hemorrhage (PH1 and PH2)
timeFrame: 48 hours
measure: proportion of hemorrhagic transformation
timeFrame: 7 Days
measure: any bleeding events
timeFrame: 7 Days
Locations:
city: Shenyang
country: China
facility: Department of Neurology, General Hospital of Northern Theater Command
Study officials:
affiliation: General Hospital of Shenyang Military Region
name: Chen Hui-Sheng, Doctor
role: STUDY_DIRECTOR
References:
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.