Brief Summary

This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design. Up to 4,000 patients with presumed acute ischemic stroke (AIS) will be followed for 90 days (or until death, if prior to 90 days). The end of the trial is defined as the date that all participants have completed their Day 90 assessment.

This domain aim is to efficiently, reliably, and simultaneously, determine the comparative effectiveness of intravenous thrombolysis (IVT) using standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) in all patients who present to hospital with acute ischemic stroke and are considered for intravenous thrombolysis. In addition, this domain also seeks to study standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) vs. no TNK upfront with rescue IA TNK if necessary (in those eligible for emergency EVT) and no TNK upfront in those who have taken DOACs during the preceding 48 hours. This domain therefore seeks to generate more robust randomized evidence to guide clinicians in their decisions over the balance of risks and treatment with intravenous thrombolysis with tenecteplase wherever such evidence is currently insufficient.

This domain will currently evaluate four research questions in relation to the use of IVT with tenecteplase:

1. In patients with recent (48 hours) intake of a standard-dose direct oral anticoagulant (DOAC), how should IVT be used? - Use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg) or not at all.
2. In patients planned to be treated with endovascular thrombectomy, how should tenecteplase be used? -Treat with IV tenecteplase (standard- or low-dose) or not at all.
3. In any patient receiving IVT, what is the optimal dose of tenecteplase? - use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg).
4. To what extent is the treatment effect of standard- vs. low-dose tenecteplase modified by key patient characteristics, such as diabetes, prior antiplatelet therapy, renal failure, or frailty, old age or having a heavy burden of cerebral small vessel disease on brain imaging.

Conditions

• Acute Ischemic Stroke AIS
• Stroke Acute
• Stroke, Acute, Stroke Ischemic

Intervention / Treatment

• Drug: Tenecteplase

Primary Outcome Measures

• A reduction of functional dependence analyzed across the whole distribution of outcomes assessed on the modified Rankin Scale (mRS), (From enrollment to the Day 90 assessment - Day 90 outcomes are assessed in a blinded manner)
  Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.

Countries

Australia, Canada

Locations and Investigators

• The George Institute for Global Health, Sydney, Australia (Not yet recruiting)
  • Xiaoying Chen, PHD
  • Craig Anderson, MD (Principal Investigator)
• Royal Prince Alfred Hospital, Sydney, Australia (Recruiting)
  • Timothy Ang, MD (Principal Investigator)
• Monash University (Box Hill), Melbourne, Australia (Recruiting)
  • Tessa Busch
  • Philip Choi, MD (Principal Investigator)
• University of Calgary, Calgary, Canada (Recruiting)
  • Carol C Kenney, RN
  • Michael D Hill, MD
  • Michael D Hill, MD (Principal Investigator)
• Medicine Hat Regional Hospital, Medicine Hat, Canada (Not yet recruiting)
  • Chloe Kilkenny, RN
  • Herbert Alejandro Manosalva, MD (Principal Investigator)
• Red Deer Regional Hospital, Red Deer, Canada (Not yet recruiting)
  • Elaine Shand, RN
  • Oje Imoukheude, MD (Principal Investigator)
• University of Alberta, Edmonton, Canada (Recruiting)
  • Paige Fairall
  • Emily Sugars
  • Brian Buck, MD (Principal Investigator)
• Kelowna Regional Hospital, Kelowna, Canada (Not yet recruiting)
  • Aleksander Tkach, MD (Principal Investigator)
• Royal Columbian Hospital, New Westminster, Canada (Not yet recruiting)
  • Vishaya Naidoo
  • George Medvedev, MD (Principal Investigator)
• University of British Columbia, Vancouver, Canada (Recruiting)
  • Geni Maclean, RN,
  • Carson Ma, RN,
  • Thalia S Field, MD (Principal Investigator)
• Brandon Regional Hospital, Brandon, Canada (Not yet recruiting)
  • Leanne Anderson
  • Arturo Tamayo Tamayo, MD (Principal Investigator)
• University of Manitoba - Winnipeg Health Science Centre, Winnipeg, Canada (Recruiting)
  • Nishita Singh, Dr.
  • Nishita Singh, MD (Principal Investigator)
• Queen Elizabeth II Health Science Center (Halifax), Halifax, Canada (Not yet recruiting)
  • Sherry Hu, MD (Principal Investigator)
• Health Sciences North Horizon Sante-Nord, Greater Sudbury, Canada (Recruiting)
  • Mythili Velma
  • Ravinder Singh, MD (Principal Investigator)
• McMaster University Hamilton Health Sciences Centre, Hamilton, Canada (Recruiting)
  • Kanchana Ratnayake
  • Lucianna Catanese, MD (Principal Investigator)
• Kingston General Hospital, Kingston, Canada (Not yet recruiting)
  • Shirin Jalini, MD (Principal Investigator)
• Lawson Health Research Institute- London, London, Canada (Not yet recruiting)
  • Beth Beauchamp, RN
  • Lindsay Lindsay.Lambourn@lhsc.on.ca, RN
  • Jennifer Mandzia, MD (Principal Investigator)
• Ottawa Hospital Research Institute, Ottawa, Canada (Recruiting)
  • Brian Dewar, MS
  • Dariush Dowlatshahi, MD (Principal Investigator)
• St. Michael's Hospital, Toronto, Canada (Recruiting)
  • Pawell Kostyrko
  • Alexandra Muccilli, MD (Principal Investigator)
• Sunnybrook Health Science Centre, Toronto, Canada (Recruiting)
  • Richard Swartz, MD
  • Richard Swartz, MD (Principal Investigator)
• Queen Elizabeth Hospital (PEI), Charlottetown, Canada (Recruiting)
  • Heather Williams, MD (Principal Investigator)
• Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Canada (Not yet recruiting)
  • Alex Poppe, MD (Principal Investigator)
• CIUSSS de l'Estrie - CHUS Fleurimont Hôpital (Sherbrooke), Sherbrooke, Canada (Not yet recruiting)
  • Caroline Cayer, RN
  • Francois Moreau, MD (Principal Investigator)
• Royal University Hospital, Saskatoon, Canada (Recruiting)
  • Cassandra Tyson
  • Gary Hunter, MD (Principal Investigator)

Study Officials

• Bijoy K Menon, MD, MSc (Principal Investigator) — University of Calgary
• Craig Anderson, MD, Ph.D. (Principal Investigator) — The George Institute
• Dariush Dowlatshahi, MD, Ph.D. (Principal Investigator) — Ottawa Hospital Research Institute
• Mohammed Almekhlafi,, MD, MSc (Principal Investigator) — University of Calgary
• Xiaoying Chen, Ph.D. (Principal Investigator) — The George Institute