NORADRENALINE TARTRATE for Ischemic stroke|Stroke

Inclusion criteria

• {"criterion_text":"-\tAcute ischemic stroke < 72 h in a perforating artery territory on brain MRI\n-\tEarly neurological deterioration or fluctuation, attested by the neurologist in charge, defined by a ≥ 3-point increase in global NIHSS score OR a 2-point increase on motor (including hand motricity) or ataxia score, whether this deterioration is transient or permanent\n-\tTime between the last neurological deterioration and randomization < 6 hours\n-\tAge ≥ 18 years\n-\tContraception required in women of childbearing potential (Intra-uterine device, hormonal contraception associated with inhibition of ovulation (combined or progestogen-only; oral, intravaginal or transdermal), Female Sterilization, Vasectomised partner, sexual abstinence)\n-\tBeneficiary of a health insurance system"}

Exclusion criteria

• {"criterion_text":"-\tPre-Stroke Modified Rankin Score > 3\n-\tLarge artery atherosclerosis (ipsilateral atherosclerotic stenosis > 50%), intra and extracranial dissection, or cardio-embolic stroke mechanisms\n-\tKnown hypersentivity to norepinephrine\n-\tPoor venous access not allowing norepinephrine administration in accordance with the protocol’s administration criteria (except if indication for placement of a long catheter as part as routine care)\n-\tDrugs with important interactions with norepinephrine: monoamine oxidase inhibitors (including reversible, non-selective agents such as linezolid), tricyclic antidepressants, entacapone. Pregnancy or breastfeeding\n-\tSignificant arrhythmia including atrial fibrillation, acute coronary syndrome, significant congestive heart failure, hypertrophic cardiomyopathy\n-\tPregnancy or breastfeeding.\n-\tContraindication to brain Magnetic Resonance Imaging (MRI)\n-\tHigh risk of intracerebral hemorrhage defined on brain magnetic resonance imaging (MRI) by the presence of the following isolated or associated criteria: \tcerebral microbleeds >10 \tnon traumatic focal superficial siderosis \themorrhagic transformation of the present ischemic stroke \tprevious history of intracerebral hemorrhage (symptomatic or asymptomatic identified on brain MRI) \tintracranial vascular malformation or tumor with suspected risk of rupture or bleeding\n-\tPrior intravenous thrombolysis < 24 hours and 24h post-thrombolysis required brain imaging (CT or MRI) to exclude haemorrhagic transformation of acute ischemic stroke\n-\tRequirement for anticoagulation in the first 7 days after randomization (except subcutaneous low molecular weight heparins for prevention of deep venous thrombosis)\n-\tSystolic blood pressure (SBP) > 200 mmHG and/or mean arterial pressure (MAP) ≥ 110mmHG at inclusion"}

Primary endpoints

• {"endpoint_text":"- Functional independence defined as modified Rankin Scale (mRS) 0-2, or return to pre-stroke mRS, assessed at 90 days","definition_or_measurement_approach":"The assessment of the clinical outcome at 90 days (±15 days) will be performed by a qualified independent assessor blinded to treatment allocation."}

Secondary endpoints

• {"endpoint_text":"-\tTwo outcomes will be used to assess 90-day functional outcomes: Ordinal (shift) modified Rankin scale at 90 days, and rate of 90-day excellent functional outcome (mRS 0-1)","definition_or_measurement_approach":"Ordinal (shift) mRS at 90 days; proportion with mRS 0-1 at 90 days (±15 days), assessed by qualified independent blinded assessor."}
• {"endpoint_text":"-\tEarly neurological improvement defined as a reduction of at least 3 points on the National Institutes of Health Stroke Scale (NIHSS) at the end of NorEpinephrine (NE) infusion and at 7 days compared to the NIHSS at the NE initiation, or a NIHSS score of 0 or 1 at the end of NE infusion and at 7 days, evaluated by a stroke neurologist","definition_or_measurement_approach":"Reduction ≥3 points on NIHSS or NIHSS 0-1 at end of NE infusion and at 7 days compared to NIHSS at NE initiation; evaluated by a stroke neurologist."}
• {"endpoint_text":"-\tMortality from any cause at 90 days","definition_or_measurement_approach":"All-cause mortality assessed at 90 days (±15 days)."}
• {"endpoint_text":"-\tPrimary Care Post-Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) at 90 days","definition_or_measurement_approach":"PC-PTSD-5 questionnaire administered at 90 days."}
• {"endpoint_text":"-\tHospital Anxiety and Depression (HAD) Scale at 90 days","definition_or_measurement_approach":"HAD scale administered at 90 days."}
• {"endpoint_text":"-\tMontreal Cognitive Assessment (MOCA) at 90 days","definition_or_measurement_approach":"MOCA administered at 90 days."}
• {"endpoint_text":"- The main predictive factor of interest is the achievement of the target pressure (at least 24h with a PAM between 110 and 120mmH).","definition_or_measurement_approach":"Achievement of target mean arterial pressure (MAP) defined as at least 24 hours with a PAM/MAP between 110 and 120 mmHg."}
• {"endpoint_text":"-\tSymptomatic intracerebral hemorrhage defined by parenchymal hematoma type 2 combined with an increase in the NIHSS score of at least 4 points.","definition_or_measurement_approach":"Symptomatic ICH defined as parenchymal hematoma type 2 plus NIHSS increase ≥4 points."}
• {"endpoint_text":"-\tNorepinephrine (NE) extravasation associated with tissue injury requiring medical or surgical intervention (cf 10. Management of adverse events): peripheral intravenous must be assessed on initiation and every 1 hour while NE administration by nurses.","definition_or_measurement_approach":"NE extravasation causing tissue injury requiring medical/surgical intervention; peripheral IV site assessed at initiation and hourly during NE infusion."}
• {"endpoint_text":"-\tAcute coronary syndrome at 7 days","definition_or_measurement_approach":"Occurrence of acute coronary syndrome within 7 days."}
• {"endpoint_text":"-\tCongestive heart failure at 7 days","definition_or_measurement_approach":"Occurrence of congestive heart failure within 7 days."}
• {"endpoint_text":"-\tTachyarrhythmia at 7 days","definition_or_measurement_approach":"Occurrence of tachyarrhythmia within 7 days."}
• {"endpoint_text":"-\tHeadache, during NE infusion.","definition_or_measurement_approach":"Incidence of headache during NE infusion."}
• {"endpoint_text":"-\tChest pain during NE infusion.","definition_or_measurement_approach":"Incidence of chest pain during NE infusion."}
• {"endpoint_text":"-\tBradycardia","definition_or_measurement_approach":"Occurrence of bradycardia during observation period."}
• {"endpoint_text":"-\tDysuria during NE infusion.","definition_or_measurement_approach":"Incidence of dysuria during NE infusion."}
• {"endpoint_text":"-\tDyspnea during NE infusion.","definition_or_measurement_approach":"Incidence of dyspnea during NE infusion."}
• {"endpoint_text":"-\tThe length of in-hospital stay will be measured from the date of admission in the emergency unit and the date of hospital discharge.","definition_or_measurement_approach":"Length of hospital stay measured from emergency admission date to hospital discharge date."}
• {"endpoint_text":"-\tRehabilitation will comprise need of hospitalization and length of stay in rehabilitation centers.","definition_or_measurement_approach":"Need for rehabilitation hospitalization and length of stay in rehabilitation centers will be recorded."}

France

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

581

Number Of Sites

15

Number Of Participants

358

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Bordeaux

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France