Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine (PRESSURE)

University Hospital of Bordeaux

Status and phase: Enrolling; Phase 3

Conditions: Stroke, Acute; Stroke, Ischemic

Treatments: Drug: Peripheral intravenous norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT06059144

CHUBX 2022/23

Details and patient eligibility

About

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.

Full 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.

Enrollment: 358 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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358 participants in 2 patient groups

Induced hypertension using norepinephrine

Experimental group

Description:

Standard care and peripheral intravenous norepinephrine. Norepinephrine (dilution: 10µg/ml, initial dose: 0.04µg/kg/min) will be titrated until MAP is between 110 and 120mmHG (with a maximal systolic blood pressure of 210mmHG) Gradually decrease of norepinephrine will start after 24h of NIHSS stabilization. Standard care includes antithrombotic treatments according to the physician's choice and ESO recommendations

Treatment:

Drug: Peripheral intravenous norepinephrine

Standard care

No Intervention group

Description:

Standard care includes antithrombotic treatments according to the physician's choice and ESO recommendations