Acute ischemic stroke due to proximal large vessel occlusion
Conditions
Interventions
Product Name: 2-Iminobiotin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 2-iminobiotin
Other descriptive name: 2-IMINOBIOTIN
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
Haaglanden Medisch Centrum
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults (age > 18 years for males and age >49 years for females) • A clinical diagnosis of AIS • Disabling stroke defined as a baseline NIH stroke scale score ? 5 • Alberta Stroke Program Early CT score (ASPECTS) > 4 on CT (or MRI) • Presence of an intracranial LVO of the anterior circulation (distal ICA, M1 or proximal M2 segment of the MCA) on CTA, MRA or DSA • Start of EVT (arterial access puncture) possible within the first 6 hours after stroke onset or last seen well • EVT with declared first endovascular approach as either stent retriever, aspiration device or a combined approach • Pre-stroke independent functional status in activities of daily living (mRS =2) 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: • Contraindication to EVT or EVT > 6 hours after symptom onset (or last seen well) • No informed consent • Evidence of a large core of established infarction defined as ASPECTS 0-4. • Evidence of absence/poor collateral circulation on CTA (Tan collateral score of 0 or 1)26. • Known co-morbidity with a life expectancy of 2 • Intent to use any endovascular device other than a stent retriever or clot aspiration device or intra-arterial medications as the initial thrombectomy approach. • History of life threatening allergy (more than rash) to contrast medium • Evidence of acute hemorrhage on CT, MRI · Significant mass effect with midline shift. · Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation) · Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or if known a eGFR < 20 mL/min. *As 2-IB has not been tested yet for embryonic toxicity and limited pre- and postnatal development studies have been performed, women who can be pregnant must not be included be in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study will be a prospective, Phase 2, randomised controlled, single centre study with the primary objective to evaluate the safety and tolerability of 2-Iminobiotin when administered to patients with acute ischemic stroke due to large vessel occlusion, treated with intravenous thrombolysis and/or endovascular therapy. ;Secondary Objective: The secondary objective will be to study preliminary efficacy.;Primary end point(s): The main study parameters used for evaluating the short-term safety and tolerability will be vital signs (heart frequency, blood pressure and oxygen saturation) before and during 24 hours after administration of the study drug and the need for clinical intervention. Furthermore, the occurrence of (serious) adverse events until 7 days will be recorded on the neurology department or until discharge from the neurology department, whichever occurs earlier. For evaluation of the pharmacokinetics profile of 2-IB, 4 plasma samples will be analysed at different intervals (4 hours, 24 hours, 25 hours, and 28 hours after study medication) Pharmacokinetic parameters to be determined will include Cmax, AUC, Tmax, T1/2, clearance (Cl), and volume of distribution (Vd);Timepoint(s) of evaluation of this end point: Vital signs: during 24 hours of treatment Adverse events: 7 days Pharmacokinetics: during 24 hours of treatment and 4 hours after treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Stroke Severity measured with the NIH stroke scale (NIHSS) at 24 hours and at discharge or at 7 days, whichever occurs earlier. 2. Infarct volume measured with MRI at 24-48 hours. In case of contraindication(s) for MRI, CT/CTA will be performed at day 5 or discharge. 3. Embolization in new territory on angiography during EVT or infarction in new territory on 24-48h MRI (or CT) 4. Vessel recanalization at 24 hours with MRA (or CTA in case of contraindications for MRI) 5. Any postintervention intracranial haemorrhage on neuroimaging within 48 hours. 6. Blood investigation (CBC, electrolytes, serum creatinine, serum glucose) at 24 hours 7. Blood investigation, biomarker neurofilament light at 24 hours and at 7 days or discharge from hospital, whichever occurs earlier and and neuron specific enolase at 24hr and 48 hr. 8. Cognitive assessment using the Cognitive Assessment scale for Stroke Patients (CASP) at 7 days or at discharge from hospital, whichever occurs earlier;Timepoint(s) of evaluation of this end point: 1. Stroke Severity (NIHSS) at 24 hours and at discharge or at 7 days, whichever occurs earlier. 2. Infarct volume at 24-48 hours. 3. Embolization in new territory on angiography or at 24-48h MRI 4. Vessel recanalization at 24 hours with MRA 5. Any postintervention intracranial haemorrhage on neuroimaging within 48 hours. 6. Blood investigation at 24 hours 7. biomarker neurofilament light at 24 hours and at 7 days and neuron specific enolase at 24 hours and 48 hours 8. Cognitive assessment at 7 days or at discharge from hospital, whichever occurs earlier | — |
Countries
Netherlands
Contacts
Public ContactNeurology department
Haaglanden Medisch Centrum
Outcome results
None listed