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

Primary Purpose

Stroke, Acute, Stroke, Ischemic

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Peripheral intravenous norepinephrine
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke, Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Induced hypertension using norepinephrine

    Standard care

    Arm 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

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

    Outcomes

    Primary Outcome Measures

    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).
    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).

    Secondary Outcome Measures

    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).
    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).
    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
    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
    Mortality
    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)
    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)
    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.
    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.
    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.

    Full Information

    First Posted
    May 26, 2023
    Last Updated
    September 22, 2023
    Sponsor
    University Hospital, Bordeaux
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06059144
    Brief Title
    Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine
    Acronym
    PRESSURE
    Official Title
    Induced Hypertension in Acute PRogrESsive Perforating Artery Stroke Using Peripheral Dilute noREpinephrine
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2024 (Anticipated)
    Primary Completion Date
    October 1, 2025 (Anticipated)
    Study Completion Date
    December 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital, Bordeaux

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stroke, Acute, Stroke, Ischemic

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    358 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Induced hypertension using norepinephrine
    Arm Type
    Experimental
    Arm 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
    Arm Title
    Standard care
    Arm Type
    No Intervention
    Arm Description
    Standard care includes antithrombotic treatments according to the physician's choice and ESO recommendations
    Intervention Type
    Drug
    Intervention Name(s)
    Peripheral intravenous norepinephrine
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    modified Rankin Scale (mRS)
    Description
    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).
    Time Frame
    Day 0
    Title
    modified Rankin Scale (mRS)
    Description
    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).
    Time Frame
    Day 90
    Secondary Outcome Measure Information:
    Title
    modified Rankin Scale (mRS)
    Description
    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).
    Time Frame
    Day 90
    Title
    modified Rankin Scale (mRS)
    Description
    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).
    Time Frame
    Day 90
    Title
    NIHSS Score
    Description
    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
    Time Frame
    Day 0
    Title
    NIHSS Score
    Description
    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
    Time Frame
    Day 7
    Title
    Mortality
    Time Frame
    Day 90
    Title
    Primary Care PTSD Screen for DSM-5 (PC-PTSD-5)
    Description
    The minimum value of the PC-PTSD-5 is 0 (best outcome) and the maximum value is 5 (worst outcome)
    Time Frame
    Day 90
    Title
    Hospital Anxiety and Depression Scale
    Description
    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)
    Time Frame
    Day 90
    Title
    Proportion of patients presenting Acute coronary syndrome
    Description
    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.
    Time Frame
    Day 7
    Title
    Proportion of patients presenting Congestive heart failure
    Description
    We will estimate the proportion of patients presenting at least one episode of congestive heart failure until day 7.
    Time Frame
    Day 7
    Title
    Proportion of patients presenting Tachyarrhythmia
    Description
    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.
    Time Frame
    Day 7

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pauline RENOU
    Phone
    05-56-79-55-20
    Email
    pauline.renou@chu-bordeaux.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pauline RENOU
    Organizational Affiliation
    University Hospital, Bordeaux
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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

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