Overview
PRESSURE is a multicenter, prospective, randomized, open, blinded end-point assessed (PROBE) trial, that aims to evaluate the efficacy and safety of drug-induced hypertension using peripheral dilute norepinephrine, in patients with acute ischemic stroke in a perforating artery territory and experiencing early neurological deterioration.
Description
Perforating artery strokes represent 25% of all ischemic strokes and is a well-known cause of progressive symptoms : 12 to 36% of cases experience early neurological deterioration in hours or days after stroke onset. A possible mechanism is hypoperfusion due to lack of a rapid development of collateral flow because of the terminal distribution of perforating arteries. Moreover, arterioles are maximally dilated within penumbra region, resulting in a cerebral autoregulation failure and a passive dependence of cerebral blood flow on arterial pressure. Thus, induced-hypertension therapy by using vasopressive agents is an attractive therapy to increase the cerebral perfusion pressure and therefore restore blood flow in the ischemic penumbra.
Eligibility
Inclusion Criteria:
- Acute ischemic stroke < 72 h in a perforating artery territory on brain MRI
- Early 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 or ataxia score, whether this deterioration is transient or permanent.
- Time between early neurological deterioration and randomization < 6 hours
- Age ≥ 18 years
- Contraception 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)
- Beneficiary of a health insurance system
Exclusion Criteria:
- - Pre-Stroke Modified Rankin Score > 3
- Contraindication to brain Magnetic Resonance Imaging (MRI)
- High risk of intracerebral hemorrhage:
- Cerebral microbleeds ≥ 10
- Non traumatic focal superficial siderosis
- Hemorrhagic transformation of the present ischemic stroke
- Previous history of intracerebral hemorrhage (symptomatic or asymptomatic identified on brain MRI)
- Intracranial vascular malformation or tumor with suspected risk of rupture or bleeding
- Prior intravenous thrombolysis < 24 hours
- Requirement for anticoagulation in the first 7 days after randomization
- Systolic blood pressure (SBP) > 180mmHG and/or mean arterial pressure (MAP) ≥ 110mmHG at inclusion
- Large artery atherosclerosis (ipsilateral atherosclerotic stenosis > 50%), intra and extracranial dissection, or cardio-embolic stroke mechanisms
- Drugs with important interactions with norepinephrine: monoamine oxidase inhibitors (including reversible, non-selective agents such as linezolid), tricyclic antidepressants, entacapone.
- Pregnancy or breastfeeding