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

Stroke, Acute Clinical Trial

— PRESSURE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06059144
• Other study ID #: CHUBX 2022/23
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: January 1, 2024
• Est. completion date: December 1, 2025

Study information

• Verified date: September 2023
• Source: University Hospital, Bordeaux
• Contact: Pauline RENOU
• Phone: 05-56-79-55-20
• Email: pauline.renou[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 358
• Est. completion date: December 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Hypertension
• Ischemic Stroke
• Stroke
• Stroke, Acute
• Stroke, Ischemic

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	modified Rankin Scale (mRS)	Functional independence defined by modified Rankin scale 0-2 or return to pre-stroke modified Rankin scale, assessed at 90 days. The assessment of the clinical outcome at 90 (±15) days will be conducted by an independent qualified assessor (blinded to patient treatment allocation). The minimal value of the modified Rankin Scale is 0 (best outcome) and the maximum value is 6 (worst outcome).	Day 0
Primary	modified Rankin Scale (mRS)	Functional independence defined by modified Rankin scale 0-2 or return to pre-stroke modified Rankin scale, assessed at 90 days. The assessment of the clinical outcome at 90 (±15) days will be conducted by an independent qualified assessor (blinded to patient treatment allocation). The minimal value of the modified Rankin Scale is 0 (best outcome) and the maximum value is 6 (worst outcome).	Day 90
Secondary	modified Rankin Scale (mRS)	Functional outcomes as measured through the ordinal (shift) modified Rankin scale. The minimal value of the modified Rankin Scale is 0 (best outcome) and the maximum value is 6 (worst outcome).	Day 90
Secondary	modified Rankin Scale (mRS)	Functional outcomes as measured through the rate of 90-day excellent functional outcome (mRS 0-1). The minimal value of the modified Rankin Scale is 0 (best outcome) and the maximum value is 6 (worst outcome).	Day 90
Secondary	NIHSS Score	c. Early neurological improvement defined as a reduction (compared to the NIHSS at the time of randomization) of at least 3 points or a score of 0 or 1 on the NIHSS	Day 0
Secondary	NIHSS Score	Early neurological improvement defined as a reduction (compared to the NIHSS at the time of randomization) of at least 3 points or a score of 0 or 1 on the NIHSS	Day 7
Secondary	Mortality		Day 90
Secondary	Primary Care PTSD Screen for DSM-5 (PC-PTSD-5)	The minimum value of the PC-PTSD-5 is 0 (best outcome) and the maximum value is 5 (worst outcome)	Day 90
Secondary	Hospital Anxiety and Depression Scale	The HAD scale provides 2 sub-scores, one on depression, and one on anxiety. Both sub-scores range from 0 (best outcome) to 21 (worst outcome)	Day 90
Secondary	Proportion of patients presenting Acute coronary syndrome	Acute Coronary Syndrome refers to ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. We will estimate the proportion of patients presenting at least one of these events until day 7.	Day 7
Secondary	Proportion of patients presenting Congestive heart failure	We will estimate the proportion of patients presenting at least one episode of congestive heart failure until day 7.	Day 7
Secondary	Proportion of patients presenting Tachyarrhythmia	Tachyarrythmia refers to a resting heart rate that exceeds 100 beats per minute. We will estimate the proportion of patients presenting at least one episode of tachyarrythmia until day 7.	Day 7