AcT
(2022)Objective
To determine whether intravenous tenecteplase (0.25 mg/kg) is non-inferior to alteplase (0.9 mg/kg) in patients with acute ischaemic stroke eligible for intravenous thrombolysis within 4.5 h of symptom onset.
Study Summary
• Symptomatic intracerebral haemorrhage at 24 h was similar: 3.4% (27/800) tenecteplase vs 3.2% (24/763) alteplase
• 90-day mortality was similar: 15.3% (122/796) tenecteplase vs 15.4% (117/763) alteplase
Intervention
Single intravenous bolus of tenecteplase 0.25 mg/kg (max 25 mg) compared with intravenous alteplase 0.9 mg/kg (max 90 mg; 0.09 mg/kg bolus followed by 60 min infusion of remaining 0.81 mg/kg).
Inclusion Criteria
Age ≥18 years, ischaemic stroke causing disabling neurological deficit, presentation within 4.5 h of symptom onset, and eligible for thrombolysis per Canadian Stroke Best Practice Recommendations.
Study Design
Arms: Tenecteplase 0.25 mg/kg IV bolus (n=806) vs Alteplase 0.9 mg/kg IV (n=771)
Patients per Arm: Tenecteplase n=806; Alteplase n=771 (ITT)
Outcome
• Symptomatic ICH at 24 h: 3.4% vs 3.2%
• 90-day all-cause mortality: 15.3% vs 15.4%
Bottom Line
Intravenous tenecteplase 0.25 mg/kg given as a single bolus is non-inferior to alteplase 0.9 mg/kg (bolus + infusion) for 90–120 day functional outcome (mRS 0–1) in acute ischaemic stroke patients eligible for thrombolysis within 4.5 h, with similar safety. Tenecteplase is a reasonable alternative to alteplase as standard-of-care thrombolytic.
Major Points
- First phase 3 RCT to demonstrate non-inferiority of tenecteplase 0.25 mg/kg vs alteplase 0.9 mg/kg for 90–120 day mRS 0–1 in acute ischaemic stroke within 4.5 h.
- Primary outcome (mRS 0–1 at 90–120 days): 36.9% tenecteplase vs 34.8% alteplase; unadjusted risk difference 2.1% (95% CI –2.6 to 6.9), meeting the prespecified –5% non-inferiority threshold.
- Safety profile comparable: 24 h symptomatic intracerebral haemorrhage 3.4% vs 3.2%; 90-day mortality 15.3% vs 15.4%.
- Pragmatic, registry-linked, multicentre design across 22 Canadian primary and comprehensive stroke centres enhances generalisability.
- Single-bolus administration of tenecteplase offers workflow advantages, especially for drip-and-ship and endovascular thrombectomy candidates.
Study Design
- Study Type
- Pragmatic, multicentre, open-label, parallel-group, registry-linked, randomised, controlled, non-inferiority trial with blinded outcome assessment
- Randomization
- Yes
- Blinding
- Open-label treatment allocation; blinded (central, masked) outcome assessment via standardised telephone interviews
- Sample Size
- 1600
- Follow-up
- Up to 120 days after randomisation (primary outcome at 90–120 days)
- Centers
- 22
- Countries
- Canada
Primary Outcome
Definition: Proportion of patients with a modified Rankin Scale (mRS) score of 0–1 (intention-to-treat)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 34.8% (266/765) alteplase | 36.9% (296/802) tenecteplase | - (–2.6 to 6.9 (risk difference)) |
Limitations & Criticisms
- Open-label design (treatment allocation not masked to clinicians or patients), although outcome assessment was blinded
- Single-country (Canada) enrolment may limit generalisability to other health systems
- Race and ethnicity data not collected
- Non-inferiority margin of 5% on absolute risk difference is generous and could mask a clinically meaningful inferiority
Citation
Lancet. 2022 Jul 16-22;400(10347):161-169.