Clinical trial NCT06059144: Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine
Official title: Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stroke, Acute
Stroke, Ischemic
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: 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

Primary outcomes:
measure: modified Rankin Scale (mRS)
timeFrame: Day 0
measure: modified Rankin Scale (mRS)
timeFrame: Day 90
Secondary outcomes:
measure: modified Rankin Scale (mRS)
timeFrame: Day 90
measure: modified Rankin Scale (mRS)
timeFrame: Day 90
measure: NIHSS Score
timeFrame: Day 0
measure: NIHSS Score
timeFrame: Day 7
measure: Mortality
timeFrame: Day 90
measure: Primary Care PTSD Screen for DSM-5 (PC-PTSD-5)
timeFrame: Day 90
measure: Hospital Anxiety and Depression Scale
timeFrame: Day 90
measure: Proportion of patients presenting Acute coronary syndrome
timeFrame: Day 7
measure: Proportion of patients presenting Congestive heart failure
timeFrame: Day 7
measure: Proportion of patients presenting Tachyarrhythmia
timeFrame: Day 7
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
Study officials:
affiliation: University Hospital, Bordeaux
name: Pauline RENOU
role: STUDY_CHAIR
References: