Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke

Stroke, Acute Clinical Trial

— AcT  

Official title:

Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke: QuICR & OPTIMISE Registry Based Pragmatic Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03889249
• Other study ID #: Version 2.0 (Sponsor assigned)
• Status: Completed
• Phase: Phase 3
• Start date: December 10, 2019
• Est. completion date: April 30, 2023

Study information

• Verified date: May 2023
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1600
• Est. completion date: April 30, 2023
• Est. primary completion date: April 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Inclusion criteria is pragmatic and informed by Canadian Best Practices.

• 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)

Related Conditions & MeSH terms

• Intracranial Thrombosis
• Ischemic Stroke
• Stroke
• Stroke, Acute
• Thromboses, Intracranial
• Thrombosis

Intervention

Drug:
• Tenecteplase
Stroke Thrombolytic
• Alteplase
Stroke Thrombolytic

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Queen Elizabeth Hospital	Charlottetown	PEI
Canada	Grey Nuns Hospital	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Halifax Infirmary Queen Elizabeth II	Halifax	Nova Scotia
Canada	Hamilton Health Sciences General Hospital	Hamilton	Ontario
Canada	Kelowna General Hospital	Kelowna	B.C.
Canada	Kingston Health Science Centre	Kingston	Ontario
Canada	London Health Sciences	London	Ontario
Canada	Medicine Hat Regional Hospital	Medicine Hat	Alberta
Canada	CHUM -Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Ottawa Civic Hospital	Ottawa	Ontario
Canada	Univerisite Laval-Hopital de l'Enfant-Jesus	Québec	Quebec
Canada	Red Deer Regional Hospital	Red Deer	Alberta
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Universite de Sherbrooke	Sherbrooke	Quebec
Canada	St. Michaels Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Death within 90 days	Collect if the patient died while in the trial and the cause of death.	From Baseline- (Randomization) until Day 90
Other	Number of Patients Diagnosed with a Symptomatic ICH post-acute stroke treatment by CT/MRI	Assess any symptomatic ICH related to the tNK or tPA post treatment. AcT defines symptomatic ICH as intracerebral hemorrhage that in the opinion of the investigator is temporally related to and directly responsible for worsening of the neurological condition. While other factors may contribute to neurological worsening, the hemorrhage should, in the investigator's opinion, be the most important factor if there are multiple factors. Thus, the neurological worsening should not be explained better by any other patient condition such as evolution of infarct, hemodynamic alteration, hypoxia etc.	24 hours days from Baseline- (Randomization)
Primary	Modified Rankin Scale (mRS) 0-1 (freedom from disability)	The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 0=No symptoms, 1=No significant disability. Able to carry out all usual activities, despite some symptoms 2=Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3=Moderate disability. Requires some help, but able to walk unassisted4=Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5=Severe disability. Requires constant nursing care and attention, bedridden, incontinent.6=Dead	By telephone Follow-up between 90-120 days
Secondary	Discharge Destination	Location where the patient is living at 90-120 days from randomization. Locations include home, early supported discharge, rehabilitation facility, long term care, death.	90-120 days after randomization
Secondary	Home Time	Defined as number of days subject spends at home after index stroke event. The home time outcome will be determined through linkage with administrative data to calculate the total time in the first 90 days after index event that a stroke patient is not an inpatient.	90-120 days after randomization
Secondary	Door to needle time	Time from when the patient enters the Emergency Room until treatment with either tNK or tPA. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	Baseline-Day 1
Secondary	Door-in-door-out (DIDO) times at Primary Stroke Centres	The amount of time from when the patient enters the Emergency room to the time of discharge from the same hospital is collected. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	Baseline - Day 1
Secondary	Recanalization	Recanalization status (mTICI score) at first angiographic acquisition in patients taken to the angio-suite for the purpose of administering EVT.Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	Baseline- After Randomization- Day 1-
Secondary	Proportion of patients administered EVT	Patients receiving Endovascular Therapy after being treated with either tNK or tPA.Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	After IV thrombolysis -within the first hour after randomization - baseline-Day 1
Secondary	Door-to-groin puncture time in patients undergoing EVT	Patients receiving Endovascular Therapy after being treated with either tNK or tPA-treatment time. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	During EVT administration-Baseline- after randomization
Secondary	CT-to-puncture time in patients undergoing EVT	Patients receiving Endovascular Therapy after being treated with either tNK or tPA-treatment time. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.	Before EVT administration- baseline- after Randomization- Day 1
Secondary	% patients returning to baseline level of functioning	Patient or surrogate reported return to baseline level of functioning	By telephone Follow-up between 90-120 days