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Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN) (TALISMAN)

Primary Purpose

Ischemic Stroke

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tenecteplase

Alteplase

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Cerebral Infarction, Ischemic Stroke, Thrombolysis

Eligibility Criteria

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

Inclusion Criteria:

Age 18 to 80 years
Acute neurologic deficit with an NIHSS ≥ 4
Non-enhanced computed tomography (NECT) of the head showing no hemorrhage
Acute ischemic stroke symptoms with onset, or time last known well, clearly defined between 3 and 4.5 hours
Treatment can be initiated within 3 to 4.5 hours from symptom onset

Exclusion Criteria:

Evidence of intracranial hemorrhage on NECT
Clinical suspicion of subarachnoid hemorrhage even with normal NECT
NECT shows hypo-density greater than 1/3 cerebral hemisphere)
History of intracranial hemorrhage/stroke
Uncontrolled HTN: At time treatment begins SBP remains >185 mmHg or DBP remains >110 mmHg despite repeated measurements
Known arteriovenous malformation, neoplasm, or aneurysm
Witnessed seizure at stroke onset
Acute bleeding tendencies
Platelet count <100,000/mm3
Heparin received in prior 48 hours with elevated aPTT
Current use of an anticoagulant (Coumadin/Warfarin) irrespective of INR
Prior use (within 48 hours) of direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban)
Within prior 3 months: intracranial or spinal surgery, head trauma, or previous stroke
Arterial puncture at non-compressible site within last 7 days
Woman of child bearing age who has a positive pregnancy test
NIH stroke scale >25 (severe deficit) or <4 and no dysphasia (mild deficit) or rapidly improving
Symptoms spontaneously clearing
14 days post-operative or post major trauma
Recent gastrointestinal or urinary tract hemorrhage within the past 21 days
Recent acute MI within the past 3 months
Serum glucose <50 mg/dl or >400 mg/dL
Age >80 or less than 18
History of ischemic stroke AND diabetes mellitus
Unable to obtain consent from patient or power of attorney
Baseline mRS > 2
Consent not obtained by 20 minutes prior to closure of the therapeutic window.
The subject has been treated with a thrombolytic agent within the past 72 hours
The subject is a pregnant woman (positive serum βHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy)
The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason

Sites / Locations

The Ohio State University College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tenecteplase

Alteplase

Arm Description

Tenecteplase 0.25 mg/kg IV - Maximum dose: 25 mg

Alteplase 0.9 mg/kg IV - Maximum dose: 90 mg

Outcomes

Primary Outcome Measures

Neurological outcome

Measured by modified Rankin Scale score

Secondary Outcome Measures

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

Full Information

NCT ID

NCT02180204

First Posted

June 21, 2014

Last Updated

September 22, 2015

Sponsor

Reza Behrouz, DO

1. Study Identification

Unique Protocol Identification Number

NCT02180204

Brief Title

Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN)

Acronym

TALISMAN

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Withdrawn

Study Start Date

January 2015 (undefined)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Reza Behrouz, DO

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

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

Ischemic Stroke

Keywords

Cerebral Infarction, Ischemic Stroke, Thrombolysis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tenecteplase

Arm Type

Experimental

Arm Description

Tenecteplase 0.25 mg/kg IV - Maximum dose: 25 mg

Arm Title

Alteplase

Arm Type

Active Comparator

Arm Description

Alteplase 0.9 mg/kg IV - Maximum dose: 90 mg

Intervention Type

Drug

Intervention Name(s)

Tenecteplase

Other Intervention Name(s)

TNKase

Intervention Description

Tenecteplase 0.25 mg/kg IV - Maximum 25 mg

Intervention Type

Drug

Intervention Name(s)

Alteplase

Other Intervention Name(s)

Activase, t-PA

Intervention Description

Alteplase 0.9 mg/kg IV - Maximum: 90 mg

Primary Outcome Measure Information:

Title

Neurological outcome

Description

Measured by modified Rankin Scale score

Time Frame

90 days

Secondary Outcome Measure Information:

Title

Symptomatic intracranial hemorrhage

Description

Twenty-four hour brain CT scan showing intracranial hemorrhage in conjuction with neurological deterioration of 4 points or more on the NIHSS

Time Frame

24 hours

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: Age 18 to 80 years Acute neurologic deficit with an NIHSS ≥ 4 Non-enhanced computed tomography (NECT) of the head showing no hemorrhage Acute ischemic stroke symptoms with onset, or time last known well, clearly defined between 3 and 4.5 hours Treatment can be initiated within 3 to 4.5 hours from symptom onset Exclusion Criteria: Evidence of intracranial hemorrhage on NECT Clinical suspicion of subarachnoid hemorrhage even with normal NECT NECT shows hypo-density greater than 1/3 cerebral hemisphere) History of intracranial hemorrhage/stroke Uncontrolled HTN: At time treatment begins SBP remains >185 mmHg or DBP remains >110 mmHg despite repeated measurements Known arteriovenous malformation, neoplasm, or aneurysm Witnessed seizure at stroke onset Acute bleeding tendencies Platelet count <100,000/mm3 Heparin received in prior 48 hours with elevated aPTT Current use of an anticoagulant (Coumadin/Warfarin) irrespective of INR Prior use (within 48 hours) of direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban) Within prior 3 months: intracranial or spinal surgery, head trauma, or previous stroke Arterial puncture at non-compressible site within last 7 days Woman of child bearing age who has a positive pregnancy test NIH stroke scale >25 (severe deficit) or <4 and no dysphasia (mild deficit) or rapidly improving Symptoms spontaneously clearing 14 days post-operative or post major trauma Recent gastrointestinal or urinary tract hemorrhage within the past 21 days Recent acute MI within the past 3 months Serum glucose <50 mg/dl or >400 mg/dL Age >80 or less than 18 History of ischemic stroke AND diabetes mellitus Unable to obtain consent from patient or power of attorney Baseline mRS > 2 Consent not obtained by 20 minutes prior to closure of the therapeutic window. The subject has been treated with a thrombolytic agent within the past 72 hours The subject is a pregnant woman (positive serum βHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy) The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reza Behrouz, DO

Organizational Affiliation

The Ohio State University College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Ohio State University College of Medicine

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22435369

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.

Results Reference

background

PubMed Identifier

19273826

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.

Results Reference

background

PubMed Identifier

20185783

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.

Results Reference

background

PubMed Identifier

15692126

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. doi: 10.1161/01.STR.0000154872.73240.e9. Epub 2005 Feb 3.

Results Reference

background

PubMed Identifier

20472172

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.

Results Reference

background

PubMed Identifier

24036924

Citation

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.

Results Reference

background

PubMed Identifier

26387127

Citation

Logallo N, Kvistad CE, Thomassen L. Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke. CNS Drugs. 2015;29(10):811-8. doi: 10.1007/s40263-015-0280-9.

Results Reference

derived

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Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN)

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