Brief Summary

Study Design and Duration:

This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of REACT. It has a prospective, randomised, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design of up to 1,500 subjects with Acute Ischemic Stroke (AIS) who undergo EVT. Randomisation will be stratified by country/ region, and the IA thrombolytic agent (tenecteplase or alteplase). Minimal sufficient balance algorithm will operate within each stratum to preserve balance on key covariates while maintaining allocation randomness.

Participants 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. Primary outcome data will be determined by simplified, structured method of assessment using the modified Rankin scale (mRS), conducted through centralized telephone interviews or online media performed by central trial personnel blinded to treatment assignment and received.

Domain Interventions:

The intervention group will receive a single dose of local intraarterial thrombolysis using either tenecteplase (at a dose of 0.0625mg/kg; maximum dose of 6.25mg) or alteplase (0.225 mg/kg; maximum dose, 20mg) at the end of EVT procedure plus standard of care while the control group will receive standard of care alone. The selection of the thrombolytic agent will be determined according to local availability. The dose of intraarterial thrombolysis will be increased if the above dose meets prespecified posterior probabilities at the first or second interims.

In all eligible patients:

1. Local intra-arterial thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg\*
2. No intra-arterial thrombolysis.

* The dose of IA thrombolysis may be doubled to 0.125 mg/kg tenecteplase or 0.45 mg/kg alteplase if this dose shows futility at pre-specified interims Randomization will be stratified by country/ region, the IA thrombolytic agent used (tenecteplase or alteplase). IA thrombolysis will be administered as a one-time treatment.

Conditions

• Stroke, Acute Ischemic
• Endovascular Thrombectomy
• Acute Ischemic Stroke AIS

Intervention / Treatment

• Biological: Tenecteplase or Alteplase- depending upon availability at each treating centre
• Other: Control

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)
• University of Calgary- Foothills Medical Centre, Calgary, Canada (Recruiting)
  • Carol C Kenney, RN
  • Mohammed Almekhlafi, MD
  • Mohammed Almekhlafi, MD (Principal Investigator)
• University of Alberta, Edmonton, Canada (Not yet recruiting)
  • Paige Lesoway
  • 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 (Not yet recruiting)
  • Geni Maclean, RN
  • Carson Ma, RN
  • Thalia Field, MD (Principal Investigator)
• University of Manitoba - Winnipeg Health Science Centre, Winnipeg, Canada (Not yet recruiting)
  • Nishita Singh, Dr.
  • Nishita Singh, MD (Principal Investigator)
• Health Sciences North Horizon Sante-Nord, Greater Sudbury, Canada (Not yet recruiting)
  • Mythili Velma
  • Ravinder Singh, MD (Principal Investigator)
• Ottawa Civic Hospital, Ottawa, Canada (Not yet recruiting)
  • Dariush Dowlatshahi, MD
  • Dariush Dowlatshahi, MD (Principal Investigator)
• Sunnybrook Health Science Centre, Toronto, Canada (Not yet recruiting)
  • Richard Swartz, MD
  • Richard Swartz, MD (Principal Investigator)
• CHUM -Centre Hospitalier de l'Universite de Montreal, Montreal, Canada (Not yet recruiting)
  • Alex Poppe, MD
  • 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 (Not yet recruiting)
  • Cassandra Tyson
  • Gary Hunter, MD (Principal Investigator)

Study Officials

• Bijoy K Menon, MD (Principal Investigator) — University of Calgary
• Craig Anderson, MD (Principal Investigator) — The George Institute