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evident
Original paper
2022LancetNeurology

AcT

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial

RCTAcute ischemic stroke

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Overview

Bolus tenecteplase 0.25 mg/kg was noninferior to alteplase for excellent function at 90-120 days after disabling ischemic stroke in Canada.

Clinical takeaway

AcT supports single-bolus tenecteplase as a practical alternative to infusion alteplase for disabling ischemic stroke treated within 4.5 hours.

Key result

mRS 0-1 at 90-120 days was 36.9% with tenecteplase vs 34.8% with alteplase (unadjusted risk difference 2.1%; 95% CI -2.6 to 6.9), meeting noninferiority.

Practice impact

Tenecteplase 0.25 mg/kg (maximum 25 mg) can replace alteplase for standard thrombolysis-eligible ischemic stroke.

Evidence

Study design

Multicentre, open-label, parallel-group, registry-linked, randomised, controlled non-inferiority trial.

Enrollment

1,600

Follow-up

Modified Rankin Scale at 90-120 days; death within 90 days.

Geography

Canada

Clinical question

Is intravenous tenecteplase noninferior to alteplase for excellent functional outcome after disabling acute ischemic stroke?

Population

  • Adults 18 years or older with disabling ischemic stroke presenting within 4.5 hours and eligible for thrombolysis per Canadian guidelines.

Intervention

Intravenous tenecteplase 0.25 mg/kg to a maximum of 25 mg.

Comparator

Intravenous alteplase 0.9 mg/kg to a maximum of 90 mg (0.09 mg/kg bolus then 0.81 mg/kg over 60 minutes).

Primary outcome

Modified Rankin Scale score of 0-1 at 90-120 days in the intention-to-treat population.

Tenecteplase met the prespecified noninferiority threshold versus alteplase for excellent functional outcome.

Unadjusted risk difference / 2.1 / 95% CI -2.6 to 6.9

Key results

  • mRS 0-1 occurred in 36.9% with tenecteplase vs 34.8% with alteplase (unadjusted risk difference 2.1%; 95% CI -2.6 to 6.9), meeting the -5% noninferiority threshold.
  • The intention-to-treat population included 1577 of 1600 randomized patients.
  • Median age was 74 years; 47.9% were female.

Harms

  • 24-hour symptomatic intracerebral hemorrhage occurred in 3.4% with tenecteplase and 3.2% with alteplase.
  • Death within 90 days occurred in 15.3% with tenecteplase and 15.4% with alteplase.

Clinical Use

Practice impact

  • Tenecteplase 0.25 mg/kg (maximum 25 mg) can replace alteplase for standard thrombolysis-eligible ischemic stroke.

Applicability

  • Most applicable to adults with disabling ischemic stroke who meet usual 4.5-hour thrombolysis criteria.

Limitations

  • Treatment assignment was open-label; outcome review was blinded.
  • Noninferiority was defined by a lower 95% CI bound above -5%, not by superiority.
  • The trial was conducted in Canadian primary and comprehensive stroke centres.

Common misinterpretations

  • Noninferiority is not proof that tenecteplase is better than alteplase.
  • The primary endpoint was excellent function, not reperfusion, despite the background rationale.

Related evidence

NINDS tPA - Earlier TrialECASS III - Earlier TrialEXTEND-IA TNK - Similar Question

Citation

Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-169. doi:10.1016/S0140-6736(22)01054-6

Intravenous tenecteplase (0ยท25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.