Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN)

Ischemic Stroke Clinical Trial

— TALISMAN  

Official title:

Phase IIb Study Comparing Tenecteplase to Alteplase in Acute Ischemic Stroke Within 3 to 4.5 Hours From Symptom Onset

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02180204
• Other study ID #: 2013H000
• Secondary ID: TALISMAN
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• First received: June 21, 2014
• Last updated: September 22, 2015
• Start date: January 2015
• Est. completion date: June 2020

Study information

• Verified date: September 2015
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a double-blind parallel arm randomized trial aimed to assess efficacy and safety of intravenous Tenecteplase compared to intravenous Alteplase in eligible patients who present with symptoms of acute ischemic stroke within 3 to 4.5 hours from onset.

Description:

Patients presenting with symptoms of acute ischemic stroke (AIS) who present within 3 to 4.5 hours of symptom onset and who meet the inclusion criteria for intravenous (IV) thrombolysis will receive, in a randomized, double-blind fashion, either IV Alteplase at 0.9 mg/kg per standard protocol or IV Tenecteplase at 0.25 mg/kg with saline infusion over one hour. Patients must also have no exclusion criteria for IV thrombolysis within the 3 to 4.5 hour window. The only required imaging is non-contrasted CT of the head. Patients will be monitored according to standard post-thrombolytic care. A CT of the head will be performed at 24 hours based on standard protocol or if there is any neurological change. Neurological function at 24 hours using NIHSS and at 3 months based on modified mRS and the NIHSS.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age 18 to 80 years

2. Acute neurologic deficit with an NIHSS = 4

3. Non-enhanced computed tomography (NECT) of the head showing no hemorrhage

4. Acute ischemic stroke symptoms with onset, or time last known well, clearly defined between 3 and 4.5 hours

5. Treatment can be initiated within 3 to 4.5 hours from symptom onset

Exclusion Criteria:

1. Evidence of intracranial hemorrhage on NECT

2. Clinical suspicion of subarachnoid hemorrhage even with normal NECT

3. NECT shows hypo-density greater than 1/3 cerebral hemisphere)

4. History of intracranial hemorrhage/stroke

5. Uncontrolled HTN: At time treatment begins SBP remains >185 mmHg or DBP remains >110 mmHg despite repeated measurements

6. Known arteriovenous malformation, neoplasm, or aneurysm

7. Witnessed seizure at stroke onset

8. Acute bleeding tendencies

9. Platelet count <100,000/mm3

10. Heparin received in prior 48 hours with elevated aPTT

11. Current use of an anticoagulant (Coumadin/Warfarin) irrespective of INR

12. Prior use (within 48 hours) of direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban)

13. Within prior 3 months: intracranial or spinal surgery, head trauma, or previous stroke

14. Arterial puncture at non-compressible site within last 7 days

15. Woman of child bearing age who has a positive pregnancy test

16. NIH stroke scale >25 (severe deficit) or <4 and no dysphasia (mild deficit) or rapidly improving

17. Symptoms spontaneously clearing

18. 14 days post-operative or post major trauma

19. Recent gastrointestinal or urinary tract hemorrhage within the past 21 days

20. Recent acute MI within the past 3 months

21. Serum glucose <50 mg/dl or >400 mg/dL

22. Age >80 or less than 18

23. History of ischemic stroke AND diabetes mellitus

24. Unable to obtain consent from patient or power of attorney

25. Baseline mRS > 2

26. Consent not obtained by 20 minutes prior to closure of the therapeutic window.

27. The subject has been treated with a thrombolytic agent within the past 72 hours

28. The subject is a pregnant woman (positive serum ßHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy)

29. The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Tenecteplase
Tenecteplase 0.25 mg/kg IV - Maximum 25 mg
• Alteplase
Alteplase 0.9 mg/kg IV - Maximum: 90 mg

Locations

Country	Name	City	State
United States	The Ohio State University College of Medicine	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Reza Behrouz, DO

Country where clinical trial is conducted

United States, 

References & Publications (6)

Behrouz R. Intravenous tenecteplase in acute ischemic stroke: an updated review. J Neurol. 2014 Jun;261(6):1069-72. doi: 10.1007/s00415-013-7102-0. Epub 2013 Sep 15. Review. — View Citation

Haley EC Jr, Lyden PD, Johnston KC, Hemmen TM; TNK in Stroke Investigators. A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke. 2005 Mar;36(3):607-12. Epub 2005 Feb 3. — View Citation

Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, Fanale C, Libman R, Kwiatkowski TG, Llinas RH, Levine SR, Johnston KC, Buchsbaum R, Levy G, Levin B; Tenecteplase in Stroke Investigators. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010 Apr;41(4):707-11. doi: 10.1161/STROKEAHA.109.572040. Epub 2010 Feb 25. — View Citation

Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM, Donnan GA, Hacke W; ECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group, Allen K, Mau J, Meier D, del Zoppo G, De Silva DA, Butcher KS, Parsons MW, Barber PA, Levi C, Bladin C, Byrnes G. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010 May 15;375(9727):1695-703. doi: 10.1016/S0140-6736(10)60491-6. — View Citation

Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012 Mar 22;366(12):1099-107. doi: 10.1056/NEJMoa1109842. — View Citation

Parsons MW, Miteff F, Bateman GA, Spratt N, Loiselle A, Attia J, Levi CR. Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window. Neurology. 2009 Mar 10;72(10):915-21. doi: 10.1212/01.wnl.0000344168.05315.9d. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological outcome	Measured by modified Rankin Scale score	90 days	No
Secondary	Symptomatic intracranial hemorrhage	Twenty-four hour brain CT scan showing intracranial hemorrhage in conjuction with neurological deterioration of 4 points or more on the NIHSS	24 hours	Yes