Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial

NCT01492725 | Terminated Phase 2 DMC

• 1 other identifier: NTA1101
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 9

Brief Summary

Patients presenting to the emergency department with acute ischaemic stroke, who are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for "dual target" major vessel occlusion and mismatch to determine their eligibility for randomisation into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intra-arterial clot retrieval after IV tPA or IV tPA alone. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (2)

• Reperfusion at 24 hours (CT or MR perfusion imaging)

  24 hours post stroke onset

• Favourable clinical response at 3 days(National Institutes of Health Stroke Score - NIHSS)

  NIHSS - reduction \>/= 8 points or reaching 0-1)

  3 days post stroke onset

Secondary Outcomes (10)

• Reperfusion at 24 hrs post stroke without symptomatic intracerebral hemorrhage (CT or MR perfusion imaging)

  24 hours post stroke onset

• Recanalisation at 24 hrs post stroke (CT or MR angiography)

  24 hours post stroke onset

• Infarct growth within 24 hrs (CT and MRI)

  24 hours post stroke onset

• Stroke severity (NIHSS) at 24 hours

  24 hours post stroke onset

• Symptomatic intra-cranial hemorrhage (ECASS type 2 parenchymal hematoma on CT or MRI combined with >/=4 point deterioration in NIHSS within 36 hours of treatment).

  within 36 hours of intervention

Study Arms (2)

Intra-arterial Clot Retrieval after iv tPA

EXPERIMENTAL

Device: Intra-arterial Clot Retrieval with Solitaire device

Standard care iv tPA

ACTIVE COMPARATOR

Genetic: intravenous tissue plasminogen activator (tPA)

Interventions

Intra-arterial Clot Retrieval with Solitaire device DEVICE

Intra-arterial mechanical clot retrieval with the Solitaire device after patients have received standard therapy with intravenous tissue plasminogen activator (tPA). Clot retrieval involves cerebral angiography and takes approximately 2 hours.

Intra-arterial Clot Retrieval after iv tPA

intravenous tissue plasminogen activator (tPA) GENETIC

Standard care IV tPA therapy administered as per registered product information

Standard care iv tPA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset
• Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
• Patient"s age is ≥18 years
• Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.
• Dual target:
• Arterial occlusion on CTA or MRA of the ICA, M1 or M2
• Mismatch - Using CT or MRI with a Tmax \>6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume. a) Mismatch ratio of greater than 1.2, and b) Absolute mismatch volume of greater than 10 ml, and. c) Infarct core lesion volume of less than 70mL

You may not qualify if:

• Intracranial haemorrhage (ICH) identified by CT or MRI
• Rapidly improving symptoms at the discretion of the investigator
• Pre-stroke mRS score of ≥ 2 (indicating previous disability)
• Inability to access the cerebral vasculature in the opinion of the neurointerventional team
• Contra indication to imaging with MR with contrast agents
• Participation in any investigational study in the previous 30 days
• Any terminal illness such that patient would not be expected to survive more than 1 year
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
• Pregnant women
• Previous stroke within last three months
• Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
• Current use of oral anticoagulants and a prolonged prothrombin time (INR \> 1.6)
• Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
• Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Prior use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) is permitted.
• Clinically significant hypoglycaemia.

Sponsors & Collaborators

• Neuroscience Trials Australia: lead

Study Sites (9)

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2605, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Western Hospital

Melbourne, Victoria, 3011, Australia

Location

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Auckland Hospital

Grafton, Auckland, 1001, New Zealand

Location

Related Publications (5)

• Sarraj A, Albers GW, Mitchell PJ, Hassan AE, Abraham MG, Blackburn S, Sharma G, Yassi N, Kleinig TJ, Shah DG, Wu TY, Hussain MS, Tekle WG, Gutierrez SO, Aghaebrahim AN, Haussen DC, Toth G, Pujara D, Budzik RF, Hicks W, Vora N, Edgell RC, Slavin S, Lechtenberg CG, Maali L, Qureshi A, Rosterman L, Abdulrazzak MA, AlMaghrabi T, Shaker F, Mir O, Arora A, Martin-Schild S, Sitton CW, Churilov L, Gupta R, Lansberg MG, Nogueira RG, Grotta JC, Donnan GA, Davis SM, Campbell BCV; SELECT, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part-II Investigators. Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study. Neurology. 2023 Jan 17;100(3):e336-e347. doi: 10.1212/WNL.0000000000201384. Epub 2022 Oct 26.

  PMID: 36289001 DERIVED

• Ng FC, Churilov L, Yassi N, Kleinig TJ, Thijs V, Wu T, Shah D, Dewey H, Sharma G, Desmond P, Yan B, Parsons M, Donnan G, Davis S, Mitchell P, Campbell B. Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow). Neurology. 2022 Feb 22;98(8):e790-e801. doi: 10.1212/WNL.0000000000013210. Epub 2021 Dec 14.

  PMID: 34906976 DERIVED

• Campbell BCV, Mitchell PJ, Churilov L, Keshtkaran M, Hong KS, Kleinig TJ, Dewey HM, Yassi N, Yan B, Dowling RJ, Parsons MW, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Rice H, de Villiers L, Ma H, Desmond PM, Meretoja A, Cadilhac DA, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost. Front Neurol. 2017 Dec 14;8:657. doi: 10.3389/fneur.2017.00657. eCollection 2017.

  PMID: 29312109 DERIVED

• Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.

  PMID: 25671797 DERIVED

• Campbell BC, Mitchell PJ, Yan B, Parsons MW, Christensen S, Churilov L, Dowling RJ, Dewey H, Brooks M, Miteff F, Levi C, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Kleinig T, Scroop R, Chryssidis S, Barber A, Hope A, Moriarty M, McGuinness B, Wong AA, Coulthard A, Wijeratne T, Lee A, Jannes J, Leyden J, Phan TG, Chong W, Holt ME, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA investigators. A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA). Int J Stroke. 2014 Jan;9(1):126-32. doi: 10.1111/ijs.12206. Epub 2013 Nov 10.

  PMID: 24207098 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2011
• First Posted: December 15, 2011
• Study Start: June 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 21, 2015

Record last verified: 2014-12

Locations

AU (8); NZ (1)