Alteplase compared to tenecteplase in patients with acute ischemic stroke: Registry-based pragmatic randomized controlled trial

INTERVENTION: Trade Name: Metalyse Pharmaceutical Form: Powder and solution for solution for injection INN or Proposed INN: TENECTEPLASE CAS Number: 191588‐94‐0 Concentration unit: U unit(s) Concentration type: range Concentration number: 8000‐10000 Trade Name: Actilyse Pharmaceutical Form: Powder and solution for solution for injection INN or Proposed INN: ALTEPLASE CAS Number: 105857‐23‐6 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1‐ CONDITION: Acute ischemic stroke ; MedDRA version: 22.1 Level: LLT Classification code 10055221 Term: Ischemic stroke System Organ Class: 10029205 ‐ Nervous system disorders ; MedDRA version: 22.1 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: The main hypothesis of this clinical trial is that tenecteplase is non‐inferior to alteplase in efficacy in patients with acute ischemic stroke eligible for i.v. thrombolysis as per current guidelines. Primary end point(s): 1) Non‐inferiority of tenecteplase in efficacy terms, i.e. in the degree of functional independence at 90‐120 days after stroke; • Modified Rankin scale (mRS) – comparison of the proportion of patients with mRS 0‐1 during 90‐120 days after stroke in both study arms; Secondary Objective: not applicable Timepoint(s) of evaluation of this end point: 90‐120 days after stroke in both study arms SECONDARY OUTCOME: Secondary end point(s): 1) Discharge destination (home, early supported discharge, rehabilitation facility, long term care, death); 2) Home time (defined as number of days subject spends at home after index stroke event); 3) Actual mRS score 90‐120 day ; 4) Door to needle (DTN) time; 5) Door‐in‐door‐out (DIDO) times at Primary Stroke Centers; 6) Recanalization status (mTICI score) at first angiographic acquisition in patients taken to the angio‐suite for the purpose of administering endovascular thrombectomy (EVT); 7) Proportion of patients administered EVT; 8) Door‐to‐groin puncture time in patients undergoing EVT; 9) CT‐to‐puncture time in patients undergoing EVT; 10) Return to baseline level of functioning Timepoint(s) of evaluation of this end point: hospitalisation phase;90‐120 days after stroke in both study arms INCLUSION CRITERIA: • Clinical diagnosis of ischemic stroke (iCMP) with sudden and clear neurological deficit. • Onset of iCMP symptoms within the last 4.5 hours, with the exception of acute basilar artery occlusion, where IVT administration is accepted even after 4.5 hours from the onset of symptoms. • Age =18 years. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250