Article Figures & Data
Tables
- Table 1
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
numberWithin 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=1600mRS 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=1870mRS 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 0–1NCT02814409 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 0–2NCT03854500 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: LAANCT04202458 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=1024mRS 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 mLACTRN12613000243718 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=1274mRS 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 0–2NCT02398656 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=86For 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 hoursICH, 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 mLNCT04086147 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=740mRS 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 mLNCT04454788 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=80mRS 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 mismatchNCT04752631 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=456mRS 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 mLNCT03785678 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=600mRS 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 awakeningNCT03181360 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.;
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