European Blood Pressure Intensive Control After Stroke

Ischemic Stroke Clinical Trial

— EPICS-Pilot  

Official title:

European Blood Pressure Intensive Control After Stroke - Pilot Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04647292
• Other study ID #: 7580
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: September 2023

Study information

• Verified date: November 2020
• Source: University College Dublin
• Contact: Katrina Tobin
• Phone: +353 1 716 4576
• Email: katrina.tobin[@]ucd.ie
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 122
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Ischemic Attack, Transient
• Ischemic Stroke
• Stroke
• Transient Ischemic Attack

Intervention

Drug:
• anti-hypertensive
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.

Locations

Country	Name	City	State
n/a

Sponsors (15)

Lead Sponsor

Collaborator

University College Dublin

Attikon Hospital, Cork University Hospital, Hospital Universitario La Paz, HRB Stroke Trials Network Ireland, Mater Misericordiae University Hospital, National University of Ireland, Galway, Ireland, Newcastle University, St Vincent's University Hospital, Ireland, Tallaght University Hospital, Universitaire Ziekenhuizen Leuven, University Hospital Waterford, University of Calgary, University of Limerick, University of Oslo

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients who do not complete the study due to tolerability or other issues	Patients who are not retained in the study will give an insight into anticipated retention in the Phase 3 trial and sample size considerations.	18 months (or end of trial visit)
Other	Ability of sites to rapidly identify eligible patients from clinics and stroke units	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.	18 months (or end of trial visit)
Other	Feasibility of home blood pressure (BP) measures and diary entries	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.	18 months (or end of trial visit)
Other	Feasibility of remote (phone/video) visits	The feasibility of remote (phone/video) visits will be assessed by the proportion of patients adhering to participation in remote visit consultations	18 months (or end of trial visit)
Primary	Difference in achieved SBP	The difference in mean SBP in the intensive versus control groups, at 18 months (or end-of-trial visit)	18 months (or end of trial visit)
Secondary	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.	18 months (or end of trial visit)
Secondary	Proportions of patients assigned to target goals successfully reaching target		18 months (or end of trial visit)
Secondary	All-cause death	Time to all-cause death	18 months (or end of trial visit)
Secondary	Number of dose-titrations required		18 months (or end of trial visit)
Secondary	Time in target range	Proportion of SBP measures in the assigned target during trial participation	18 months (or end of trial visit)
Secondary	Loss to follow-up	Number of participants lost to follow-up in both treatment arms	18 months (or end of trial visit)
Secondary	Time taken to reach target range		18 months (or end of trial visit)
Secondary	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.	18 months (or end of trial visit)
Secondary	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	18 months (or end of trial visit)
Secondary	Difference in mean achieved diastolic blood pressure (DBP) between groups		18 months (or end of trial visit)
Secondary	Change in SBP and DBP from baseline to end-of-trial		18 months (or end of trial visit)
Secondary	Time required per follow up visit		18 months (or end of trial visit)
Secondary	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.	18 months (or end of trial visit)
Secondary	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.	18 months (or end of trial visit)
Secondary	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	18 months (or end of trial visit)
Secondary	Number of pre-specified adverse events		18 months (or end of trial visit)
Secondary	Qualitative patient feedback obtained via workshops and questionnaires		18 months (or end of trial visit)
Secondary	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		18 months (or end of trial visit)