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European Blood Pressure Intensive Control After Stroke (EPICS-Pilot)

Primary Purpose

Ischemic Stroke, Transient Ischemic Attack

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
anti-hypertensive
Sponsored by
University College Dublin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring ischemic stroke, transient ischemic attack, blood pressure, hypertension, recurrence, prognosis, prevention, randomized control trial, myocardial infarction, vascular events

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥40
  2. Ischaemic stroke, proven by imaging (including transient ischaemic attack with imaging evidence of acute brain ischaemia
  3. Living at home and independent (walking without the aid of another person, but may have some help for daily activities - equivalent to Rankin score 3 or less)
  4. SBP≥130mmHg at entry (average of 2 measures, seated, after resting alone in office for 5 minutes)
  5. Qualifying Stroke/TIA between 7 days and 1 year of randomization
  6. Glomerular filtration rate (eGFR) greater than or equal to 50 ml/min/m2
  7. Medically-stable and capable of participating in a randomised trial, including home BP measures, in the opinion of the study physician
  8. Willing to provide informed consent (no surrogate consent will apply)

Exclusion Criteria:

  1. Stroke/TIA due to cardio-embolism or other defined causes (eg. dissection, endocarditis, other specified)
  2. Severe stenosis of large cranio-cervical artery (>70% stenosis of cervical carotid, vertebral, or Circle of Willis artery)
  3. Medical history of primary intracerebral haemorrhage (asymptomatic cerebral microbleeds detected on brain MRI are not excluded)
  4. SBP <110mmHg after 3 minutes of standing or other contra-indication to intensive SBP lowering in opinion of treating clinician* (eg. syncope or pre-syncope, recurrent falls)
  5. Unlikely to comply with study procedures (home BP measures, follow-up visits) due to severe or fatal co-morbid illness (eg. dementia, active malignancy, severe frailty) or other factor (eg. inability to travel)
  6. Women of child-bearing potential

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Target systolic blood pressure 115-125 mmHg

    Target systolic blood pressure 130-139 mmHg

    Arm Description

    Recommended target SBP 115-125 millimetres of mercury (mmHg).

    Target SBP 130-139 mmHg (per American Stroke Association, European Stroke Organisation guidelines).

    Outcomes

    Primary Outcome Measures

    Difference in achieved SBP
    The difference in mean SBP in the intensive versus control groups, at 18 months (or end-of-trial visit)

    Secondary Outcome Measures

    Time to first composite major vascular event
    Defined as recurrent stroke, myocardial infarction, cardiac arrest, and to each component of the composite, stratified as fatal, non-fatal and total.
    Proportions of patients assigned to target goals successfully reaching target
    All-cause death
    Time to all-cause death
    Number of dose-titrations required
    Time in target range
    Proportion of SBP measures in the assigned target during trial participation
    Loss to follow-up
    Number of participants lost to follow-up in both treatment arms
    Time taken to reach target range
    Change in cognition
    Change in Montreal cognitive assessment score (range 0-30) at last follow-up compared with baseline score. A lower score indicates greater cognitive impairment.
    Quality of life score
    Change in EQ5D-5L score (5 domains assessed with scores of 1-5 ranking the severity of impairment, with higher scores indicating poorer quality of life) at last follow-up compared with baseline
    Difference in mean achieved diastolic blood pressure (DBP) between groups
    Change in SBP and DBP from baseline to end-of-trial
    Time required per follow up visit
    Feasibility of remote BP titration
    Qualitative feedback from patients on their views relating to the feasibility of home blood pressure monitoring and remote dose titration will be sought. This design feature will be carefully examined in the pilot, before incorporation into the main trial.
    Disability in intensive-SBP and guideline-based SBP target patients assessed by modified Rankin score (shift analysis and proportion with no, mild, or moderate disability, Rankin score 0-3)
    Proportion of participants with disability. The modified Rankin scale is graded from 0-6, with 0 indicating no disability and 6 indicating death.
    Number of adverse events, serious adverse events, and suspected unexpected serious adverse reactions (SUSARs)
    Difference in proportion of patients with adverse events, serious adverse events and SUSARS
    Number of pre-specified adverse events
    Qualitative patient feedback obtained via workshops and questionnaires
    Total, direct and indirect (eg. via lost income to study participants or family members) costs associated with face-to-face visits for study participants will be quantified

    Full Information

    First Posted
    November 20, 2020
    Last Updated
    November 27, 2020
    Sponsor
    University College Dublin
    Collaborators
    St Vincent's University Hospital, Ireland, Cork University Hospital, Tallaght University Hospital, University of Limerick, University of Calgary, Universitaire Ziekenhuizen KU Leuven, Attikon Hospital, Hospital Universitario La Paz, HRB Stroke Trials Network Ireland, National University of Ireland, Galway, Ireland, Mater Misericordiae University Hospital, University of Oslo, Newcastle University, University Hospital Waterford
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04647292
    Brief Title
    European Blood Pressure Intensive Control After Stroke
    Acronym
    EPICS-Pilot
    Official Title
    European Blood Pressure Intensive Control After Stroke - Pilot Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    June 1, 2021 (Anticipated)
    Primary Completion Date
    September 2023 (Anticipated)
    Study Completion Date
    September 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University College Dublin
    Collaborators
    St Vincent's University Hospital, Ireland, Cork University Hospital, Tallaght University Hospital, University of Limerick, University of Calgary, Universitaire Ziekenhuizen KU Leuven, Attikon Hospital, Hospital Universitario La Paz, HRB Stroke Trials Network Ireland, National University of Ireland, Galway, Ireland, Mater Misericordiae University Hospital, University of Oslo, Newcastle University, University Hospital Waterford

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Stroke is the third most common cause of death worldwide and the leading cause of disability. High blood pressure is an important risk factor for stroke. Lowering a person's blood pressure reduces the risk of future stroke or heart attack. However, the optimal target blood pressure after a person suffers a stroke is not known. This is a study designed to establish the feasibility of a larger clinical trial, the aim of which will be to find out if greater blood pressure lowering is safe and effective for patients who suffer a stroke.
    Detailed Description
    Background: Stroke is the third leading cause of global death, the leading cause of acquired disability and contributes substantially to dementia, cognitive decline, and healthcare costs. Global epidemiological studies such as INTERSTROKE and the Global Burden of Disease study estimated that hypertension is the leading modifiable risk factor for stroke, with a population attributable risk of approximately 50%. Recurrent vascular events (stroke, coronary events, vascular death) cause significant morbidity in ischaemic stroke survivors, affecting approximately 30% at 5 years. Blood-pressure reduction is a proven, inexpensive strategy to prevent stroke with benefits widely-generalizable in developed and developing countries. No randomised trials have demonstrated the efficacy and safety of SBP reduction to prevent secondary vascular events after ischaemic stroke to levels of about 120mmHg compared with 130-139mmHg. Consequently, most guidelines recommend reduction of systolic blood pressure (SBP) less than 140mmHg. Aim: The aim is to conduct an initial pilot randomised trial in Ireland and 7 leading European centres involved in the European Stroke Organisation Trials Alliance. This feasibility study will assess key design aspects and establish trial governance, data management, and procedures in preparation for a larger definitive trial. Methods: Design: Prospective, open-label, blinded endpoint assessed (PROBE) randomised, parallel-group pilot trial, comparing safety, efficacy, and other feasibility measures of two target SBP goals (intervention 115-125 mmHg, control 130-139 mmHg).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ischemic Stroke, Transient Ischemic Attack
    Keywords
    ischemic stroke, transient ischemic attack, blood pressure, hypertension, recurrence, prognosis, prevention, randomized control trial, myocardial infarction, vascular events

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    122 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Target systolic blood pressure 115-125 mmHg
    Arm Type
    Experimental
    Arm Description
    Recommended target SBP 115-125 millimetres of mercury (mmHg).
    Arm Title
    Target systolic blood pressure 130-139 mmHg
    Arm Type
    Active Comparator
    Arm Description
    Target SBP 130-139 mmHg (per American Stroke Association, European Stroke Organisation guidelines).
    Intervention Type
    Drug
    Intervention Name(s)
    anti-hypertensive
    Intervention Description
    The recommended target SBP will be 115-125 mmHg in the intervention arm. A medication algorithm based on the SPRINT trial protocol will be provided. The final choice and dose of antihypertensive treatment(s) will be at the discretion of the treating clinicians. If no contra-indications, indapamide or other thiazide diuretic and/or angiotensin-converting enzyme (ACE) inhibitor (perindopril or other) will be encouraged as initial therapy, with long-acting calcium-channel antagonists (eg.amlodipine) encouraged as third-line therapy. At scheduled face-to-face or remote follow-up, patients will have their home blood pressure monitoring diary reviewed by the study team. If SBP is out of the allocated target range, a prescription to titrate (up or down) antihypertensive medication will be given to the patient.
    Primary Outcome Measure Information:
    Title
    Difference in achieved SBP
    Description
    The difference in mean SBP in the intensive versus control groups, at 18 months (or end-of-trial visit)
    Time Frame
    18 months (or end of trial visit)
    Secondary Outcome Measure Information:
    Title
    Time to first composite major vascular event
    Description
    Defined as recurrent stroke, myocardial infarction, cardiac arrest, and to each component of the composite, stratified as fatal, non-fatal and total.
    Time Frame
    18 months (or end of trial visit)
    Title
    Proportions of patients assigned to target goals successfully reaching target
    Time Frame
    18 months (or end of trial visit)
    Title
    All-cause death
    Description
    Time to all-cause death
    Time Frame
    18 months (or end of trial visit)
    Title
    Number of dose-titrations required
    Time Frame
    18 months (or end of trial visit)
    Title
    Time in target range
    Description
    Proportion of SBP measures in the assigned target during trial participation
    Time Frame
    18 months (or end of trial visit)
    Title
    Loss to follow-up
    Description
    Number of participants lost to follow-up in both treatment arms
    Time Frame
    18 months (or end of trial visit)
    Title
    Time taken to reach target range
    Time Frame
    18 months (or end of trial visit)
    Title
    Change in cognition
    Description
    Change in Montreal cognitive assessment score (range 0-30) at last follow-up compared with baseline score. A lower score indicates greater cognitive impairment.
    Time Frame
    18 months (or end of trial visit)
    Title
    Quality of life score
    Description
    Change in EQ5D-5L score (5 domains assessed with scores of 1-5 ranking the severity of impairment, with higher scores indicating poorer quality of life) at last follow-up compared with baseline
    Time Frame
    18 months (or end of trial visit)
    Title
    Difference in mean achieved diastolic blood pressure (DBP) between groups
    Time Frame
    18 months (or end of trial visit)
    Title
    Change in SBP and DBP from baseline to end-of-trial
    Time Frame
    18 months (or end of trial visit)
    Title
    Time required per follow up visit
    Time Frame
    18 months (or end of trial visit)
    Title
    Feasibility of remote BP titration
    Description
    Qualitative feedback from patients on their views relating to the feasibility of home blood pressure monitoring and remote dose titration will be sought. This design feature will be carefully examined in the pilot, before incorporation into the main trial.
    Time Frame
    18 months (or end of trial visit)
    Title
    Disability in intensive-SBP and guideline-based SBP target patients assessed by modified Rankin score (shift analysis and proportion with no, mild, or moderate disability, Rankin score 0-3)
    Description
    Proportion of participants with disability. The modified Rankin scale is graded from 0-6, with 0 indicating no disability and 6 indicating death.
    Time Frame
    18 months (or end of trial visit)
    Title
    Number of adverse events, serious adverse events, and suspected unexpected serious adverse reactions (SUSARs)
    Description
    Difference in proportion of patients with adverse events, serious adverse events and SUSARS
    Time Frame
    18 months (or end of trial visit)
    Title
    Number of pre-specified adverse events
    Time Frame
    18 months (or end of trial visit)
    Title
    Qualitative patient feedback obtained via workshops and questionnaires
    Time Frame
    18 months (or end of trial visit)
    Title
    Total, direct and indirect (eg. via lost income to study participants or family members) costs associated with face-to-face visits for study participants will be quantified
    Time Frame
    18 months (or end of trial visit)
    Other Pre-specified Outcome Measures:
    Title
    Number of patients who do not complete the study due to tolerability or other issues
    Description
    Patients who are not retained in the study will give an insight into anticipated retention in the Phase 3 trial and sample size considerations.
    Time Frame
    18 months (or end of trial visit)
    Title
    Ability of sites to rapidly identify eligible patients from clinics and stroke units
    Description
    The inclusion of prevalent cases already attending stroke clinics or discharged from stroke units within the last year is an important design feature, aimed to rapidly accrue patients into the trial and thus to maximise the duration of follow-up within the terms allowed by funders. This outcome will be judged on the basis of qualitative feedback from participating sites.
    Time Frame
    18 months (or end of trial visit)
    Title
    Feasibility of home blood pressure (BP) measures and diary entries
    Description
    This outcome will be judged on the basis of qualitative feedback from participants and the the proportions of participants adhering to the use of home blood pressure diaries.
    Time Frame
    18 months (or end of trial visit)
    Title
    Feasibility of remote (phone/video) visits
    Description
    The feasibility of remote (phone/video) visits will be assessed by the proportion of patients adhering to participation in remote visit consultations
    Time Frame
    18 months (or end of trial visit)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥40 Ischaemic stroke, proven by imaging (including transient ischaemic attack with imaging evidence of acute brain ischaemia Living at home and independent (walking without the aid of another person, but may have some help for daily activities - equivalent to Rankin score 3 or less) SBP≥130mmHg at entry (average of 2 measures, seated, after resting alone in office for 5 minutes) Qualifying Stroke/TIA between 7 days and 1 year of randomization Glomerular filtration rate (eGFR) greater than or equal to 50 ml/min/m2 Medically-stable and capable of participating in a randomised trial, including home BP measures, in the opinion of the study physician Willing to provide informed consent (no surrogate consent will apply) Exclusion Criteria: Stroke/TIA due to cardio-embolism or other defined causes (eg. dissection, endocarditis, other specified) Severe stenosis of large cranio-cervical artery (>70% stenosis of cervical carotid, vertebral, or Circle of Willis artery) Medical history of primary intracerebral haemorrhage (asymptomatic cerebral microbleeds detected on brain MRI are not excluded) SBP <110mmHg after 3 minutes of standing or other contra-indication to intensive SBP lowering in opinion of treating clinician* (eg. syncope or pre-syncope, recurrent falls) Unlikely to comply with study procedures (home BP measures, follow-up visits) due to severe or fatal co-morbid illness (eg. dementia, active malignancy, severe frailty) or other factor (eg. inability to travel) Women of child-bearing potential
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Katrina Tobin
    Phone
    +353 1 716 4576
    Email
    katrina.tobin@ucd.ie

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    IPD Sharing Plan Description
    The investigators are open to considering requests for collaborative projects.
    Citations:
    PubMed Identifier
    36398903
    Citation
    Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.
    Results Reference
    derived

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