Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke

NCT ID: NCT03889249

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-10
• Study Completion Date: 2023-04-30

Brief Summary

The proposed trial is a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per standard care. All patients will have standard of care medical management on an acute stroke unit. There are no additional trial specific management recommendations. Patients will be followed for approximately 90-120 days.

Detailed Description

There are two established therapies for acute ischemic stroke, namely intravenous alteplase and endovascular thrombectomy (EVT). The guiding principles behind these therapies are fast, effective and safe reperfusion of ischemic brain. Patients with acute ischemic stroke presenting within 4.5 hours from symptom onset are administered intravenous alteplase. If there is evidence of large vessel occlusion (LVO), these patients are transferred to the nearest comprehensive stroke center (CSC) for EVT.Physicians, hospitals and health systems are focused on implementing efficient triaging systems and workflow processes to improve speed and efficacy of administration of these life-saving therapies. Although efforts over the years with intravenous alteplase administration has resulted in improvement in efficiency metrics like door to needle time (DTN) and door-in-door-out (DIDO) time, these metrics are still not optimal, and the therapy is underutilized. Physicians continue to have concerns about low early reperfusion rates, increased risk of symptomatic intracerebral hemorrhage and challenges with drug administration (bolus + 60-minute infusion) with intravenous alteplase.

Recent phase II trials have shown that intravenous tenecteplase is potentially safer and may achieve higher early reperfusion rates than alteplase in patients with acute ischemic stroke. Bolus administration makes tenecteplase easier to administer than alteplase (which requires infusion pumps). Transfer of patients from primary stroke centers (PSC) to comprehensive stroke centers (CSCs) is potentially easier without infusion pumps. Moreover, depending on the province, tenecteplase either costs the same, or even less, than alteplase. It is therefore possible that the use of intravenous tenecteplase in patients with acute ischemic stroke otherwise eligible for intravenous alteplase may result in faster administration of thrombolysis and more efficient transport to CSCs, thus saving time, reducing adverse events (intracranial hemorrhage) and potentially improving patient outcomes, while saving the health system costs. For these various reasons, robust evidence that tenecteplase is non-inferior to alteplase as an intravenous thrombolytic agent in patients with acute ischemic stroke will change current clinical practice as it did in patients with myocardial infarction. The proposed trial is therefore a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to generate real world evidence whether intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per current standard of care.

Conditions

Stroke, Acute; Thromboses, Intracranial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Tenecteplase (tNK-TPA)

The intervention group will receive intravenous tenecteplase as a single bolus as per the standard manufacturers' instructions for use. The dose administered will be 0.25 mg/kg body weight (maximum dose 25 mg) over 10-20 seconds as soon as possible after randomization. Tenecteplase has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase.

Group Type: ACTIVE_COMPARATOR

Tenecteplase

Intervention Type: DRUG

Stroke Thrombolytic

Alteplase ( tPA)

The control group will receive standard of care dosing of intravenous alteplase (0.9 mg/kg body weight, 10% bolus and 90% infusion as per standard care, maximum dose 90 mg).

Group Type: ACTIVE_COMPARATOR

Alteplase

Intervention Type: DRUG

Stroke Thrombolytic

Interventions

Tenecteplase

Stroke Thrombolytic

Intervention Type: DRUG

Alteplase

Stroke Thrombolytic

Intervention Type: DRUG

Other Intervention Names

tNK; tPA

Eligibility Criteria

Inclusion Criteria

• All patients with acute ischemic stroke eligible to receive intravenous alteplase as per standard care will be eligible for enrolment in the proposed trial.
• Patients eligible for endovascular thrombectomy in addition to intravenous thrombolysis are eligible for enrolment.

Exclusion Criteria

• Contra-indications to intravenous thrombolysis as used by treating physicians as current standard of care apply.
• The benefits of thrombolysis with intravenous alteplase in the pediatric population is unknown. Any patient < 18 years of age may therefore not be enrolled.
• Women with pregnancy known to the investigator by history or examination, without requiring pregnancy testing, may only be enrolled in consultation with an expert stroke physician (either in person or through tele-stroke)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Bijoy Menon

Stroke Neurologist, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bijoy K Menon, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

University of Calgary

Calgary, Alberta, Canada

Grey Nuns Hospital

Edmonton, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Medicine Hat Regional Hospital

Medicine Hat, Alberta, Canada

Red Deer Regional Hospital

Red Deer, Alberta, Canada

Kelowna General Hospital

Kelowna, B.C., Canada

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

Halifax Infirmary Queen Elizabeth II

Halifax, Nova Scotia, Canada

Hamilton Health Sciences General Hospital

Hamilton, Ontario, Canada

Kingston Health Science Centre

Kingston, Ontario, Canada

London Health Sciences

London, Ontario, Canada

Ottawa Civic Hospital

Ottawa, Ontario, Canada

St. Michaels Hospital

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

CHUM -Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Univerisite Laval-Hopital de l'Enfant-Jesus

Québec, Quebec, Canada

Universite de Sherbrooke

Sherbrooke, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

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Other Identifiers

Version 2.0 (Sponsor assigned)

Identifier Type: -

Identifier Source: org_study_id