Ongoing and planned clinical trials examining the efficacy and safety of TNK
| Trial Type | Trial Name | Objectives | Study design | Primary outcome | Key safety outcome | Key eligibility criteria | Registration number |
| Within 4.5 hours of onset | AcT (Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke) | To test the real-world non-inferiority of TNK efficacy compared with tPA in patients with AIS eligible for IV thrombolysis | TNK 0.25 mg/kg vs tPA 0.9 mg/kg non-inferiority Pragmatic registry-based phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=1600 | mRS at day 90–120 | Mortality and sICH | Patients with AIS eligible for IV tPA or bridging therapy | NCT03889249 |
| ATTEST 2 (Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis) | To test the superiority of TNK efficacy compared with tPA in patients with AIS eligible for IV thrombolysis | TNK 0.25 mg/kg vs tPA 0.9 mg/kg Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=1870 | mRS at day 90 | Intracranial and extracranial haemorrhage, mortality, neurological deterioration | ≥18 years old Thrombolysis initiated within 4.5 hours after onset Eligible for IV thrombolysis Premorbid mRS 0–1 | NCT02814409 | |
| NOR TEST 2 (The Norwegian Tenecteplase Stroke Trial 2) | To compare efficacy and safety of TNK vs tPA 0.9 mg/kg within 4.5 hours after onset, including wake-up stroke and before EVT | TNK 0.4 mg/kg vs tPA 0.9 mg/kg non-inferiority Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=1342 | % of mRS 0–1 at day 90 | Cerebral haemorrhages on CT/MRI within 24–48 hours and mortality | ≥18 years old Thrombolysis initiated within 4.5 hours after onset NIHSS >5 Premorbid mRS 0–2 | NCT03854500 | |
| Large vessel occlusion | BRETIS-TNK (Boosting REcanalization of Thrombectomy for Ischemic Stroke by Intra-arterial TNK) | To explore whether a combination of IA TNK and EVT can increase recanalisation rate after the first attempt of device pass | IA TNK 4 mg bolus followed by infiltration (0.4 mg/min) for 30 min Single arm phase: Not applicable N=30 | % of TICI 2b-3 | sICH | ≥18 years old LVO anterior circulation stroke eligible for EVT TOAST: LAA | NCT04202458 |
| TASTE (Tenecteplase vs Alteplase for Stroke Thrombolysis Evaluation) | To test TNK’s efficacy in patients with demonstrated LVO and target penumbral pattern as opposed to tPA within 4.5 hours | TNK 0.25 mg/kg vs tPA 0.9 mg/kg non-inferiority Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=1024 | mRS 0–1 at day 90 | sICH and all cause death | ≥18 years old Thrombolysis initiated within 4.5 hours after onset Eligible for IV thrombolysis Premorbid mRS 0–1 Imaging selection criteria: Penumbra volume >15 mL; mismatch ratio >1.8; ischaemic core <70 mL; severely hypoperfused volume <100 mL | ACTRN12613000243718 | |
| TEMPO 2 (TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion) | To test TNK’s efficacy compared with standard care, in patients of TIA or minor stroke with demonstrated LVO or near occlusion within 12 hours | TNK 0.25 mg/kg vs antiplatelets Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=1274 | mRS at day 90 | Major bleeding | ≥18 years old Treatment can be initiated within 12 hours after onset, and within 90 min of the start of CT/MRI TIA or minor stroke with NIHSS ≤5 Acute LVO or near occlusion (TICI 0 or 1) Premorbid mRS 0–2 | NCT02398656 | |
| Late time window or wake-up strokes | CHABLIS-T (CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase) | Optimal dosage determination of TNK in AIS patients in extended time window. | TNK 0.25 mg/kg vs TNK 0.32 mg/kg Phase II randomisation: Yes Open-label: Yes Blinded outcome assessment: Yes N=86 | For patients w/o EVT:>50% reperfusion at 4–6 hours and w/o sICH at 24–48 hours For patients with EVT: mTICI score ≥2b before EVT and w/o sICH at 24–48 hours | ICH, systemic bleeding and mRS 5–6 | ≥18 years old 4.5–24 hours after onset Anterior circulation AIS Premorbid mRS 0–2 Clinically significant neurological deficits Imaging selection criteria: Proven LVO or severe stenosis; mismatch ratio >1.2; ischaemic core <70 mL; absolute difference >10 mL | NCT04086147 |
| ETERNAL-LVO (Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion) | To evaluate the efficacy and safety of TNK in extended time window | TNK 0.25 mg/kg vs standard care (may include eligible IV tPA) Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=740 | mRS 0–1 or return to baseline mRS (if premorbid mRS=2) at day 90 | ICH, all cause death, infarct growth, mRS 5–6 | ≥18 years Up to 24 hours after onset or last known well Anterior circulation AIS Premorbid mRS 0–2 Imaging selection criteria: Proven LVO or extracranial ICA stenosis; mismatch ratio >1.8; ischaemic core <70 mL; absolute difference >20 mL | NCT04454788 | |
| ROSE-TNK (MRI-guided thrOmbolysis for Stroke bEyond Time Window by TNK) | To examine the feasibility and outcome of TNK in 4.5–24 hours after stroke guided by a mismatch between DWI and FLAIR | TNK 0.25 mg/kg vs standard care Phase IV randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=80 | mRS 0–1 at day 90 | ICH, any bleeding events and death | 18–80 years old 4.5–24 hours after onset NIHSS 6–25, or NIHSS ≤5 with culprit vessel occlusion or severe stenosis Premorbid mRS 0–1 Imaging selection criteria: DWI infarct <1/3 of MCA or 1/2 of ACA or 1/2 of PCA territory; infarct <70 mL; DWI/FLAIR mismatch | NCT04752631 | |
| TIMELESS (Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase) | To evaluate the efficacy and safety of TNK in extended time window | TNK 0.25 mg/kg vs placebo Phase III randomisation: Yes Blinded treatment: Yes Blinded outcome assessment: Yes N=456 | mRS at day 90 | ICH, adverse events, mortality | ≥18 years old 4.5–24 hours after onset Anterior circulation AIS Premorbid mRS 0–2 NIHSS ≥5 prior to randomisation Imaging selection criteria: Proven LVO; mismatch ratio ≥1.8; Ischaemic core <70 mL; absolute difference ≥15 mL | NCT03785678 | |
| TWIST (Tenecteplase in Wake-Up Ischaemic Stroke Trial)18 | To test TNK’s efficacy in stroke patients <4.5 hours of awakening | TNK 0.25 mg/kg+standard care vs no TNK +standard care Phase III randomisation: Yes Open label: Yes Blinded outcome assessment: Yes N=600 | mRS at day 90 | All-cause death and ICH | ≥18 years old Wake-up stroke With limb weakness with NIHSS of 3–24, or dysphasia Treatment can be initiated <4.5 hours of awakening | NCT03181360 |
ACA, anterior cerebral artery; AIS, acute ischaemic stroke; DWI, diffusion-weighted imaging; EVT, endovascular therapy; FLAIR, fluid attenuation inversion recovery; IA, intra-arterial; ICA, internal carotid artery; ICH, intracerebral haemorrhage; IV, intravenous; LAA, large artery atherosclerosis; LVO, large vessel occlusion; MCA, middle cerebral artery; mRS, modified Rankin scale; NIHSS, National Institutes of Health Stroke Scale; PCA, posterior cerebral artery; mTICI score, Modified Treatment in Cerebral Ischemia Score; sICH, symptomatic intracerebral haemorrhage; TNK, tenecteplase; TOAST, Trial of Org 10 172 in Acute Stroke Treatment; tPA, tissue plasminogen activator; tPA, tissue plasminogen activator.;