Optimal Blood Pressure for the prevenTIon of Major vAscuLar Events in Stroke Patients

Study Overview
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Brief Summary
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Elevated blood pressure (BP) consists of a major public health concern especially in low and middle income countries. Besides being a highly prevalent condition, it is also a risk factor for several major cardiovascular events including stroke (which consists of the second leading cause of death in developing countries) and coronary artery disease, and is also related to cognitive decline. The OPTIMAL Stroke trial consists of a two-arm, multicenter, randomized clinical trial designed to test whether a lower target systolic blood pressure (SBP) as compared to the currently recommended target for stroke patients will reduce the occurrence of major cardiovascular events.

Official Title
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A Randomized Controlled Trial to Assess the Effect of Intensive Blood Pressure Control on Major Cardiovascular Events in Stroke Patients

Conditions
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Ischemic Stroke, Blood Pressure, Cognitive Impairment, Vascular Diseases

Intervention / Treatment
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* Drug: Intensive Control of Systolic Blood Pressure (SBP)
* Drug: Standard control of Systolic Blood Pressure (SBP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of ischemic stroke or transient ischemic attack (TIA), considered clinically stable in the 48 hours prior to inclusion in the study. (they will be classified into a recent stroke <120 days or chronic when> 120 days), AND Systolic Blood Pressure (SBP) between 130 and 180 mmHg: 130 -180 and use of up to one antihypertensive drug; 130-170 and use of up to two drugs; 130-160 and use of up to three drugs; 130-150 and use of up to four drugs. AND Exclusion Criteria: Severe disability after the event that qualified the patient for the study, defined as a modified Rankin (mRankin) scale equal to or greater than 4. Being part of another clinical trial involving interventions for cardiovascular prevention. Body mass index > 45 kg/m2. Pregnancy or Breastfeeding. Secondary hypertension. Class IV Canadian Cardiovascular Society (CCS) Resting Angina. Acute coronary syndrome in the last six months Severe renal dysfunction with GFR < 20 mL/min/1.73m2 calculated by the CKD-EPI equation Refusal to consent. Symptomatic heart failure - Class IV New York Heart Association (NYHA) or ejection fraction <35% on Doppler echocardiography. Conditions that, at the investigators' discretion, limit the patient's participation in the study, including but not limited to the following: Recent history of alcohol and illicit drug abuse. Psychiatric comorbidities (severe depression, schizophrenia, psychosis, etc.). History of poor drug adherence and no attendance at consultations. Planning to change of address in the next four years. Planning to be absent from home city for more than three months in the next year. Residing in the same residence of another patient previously included in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Control of Systolic Blood Pressure (SBP)<br>Participants randomized into the Intensive Blood Pressure arm will have a goal of SBP <120 mm Hg. | Drug: Intensive Control of Systolic Blood Pressure (SBP)<br>* Participants in the Intensive arm have a goal of SBP <120 mm Hg. The use of angiotensin converting enzyme (ACE)-inhibitors/Angiotension receptor blockers (ARBs), Thiazide-type diuretics, calcium channel blockers (CCB), Sustained-release calcium channel blockers (CCBs) will be encouraged, preferably fixed-dose combinations of indapamide + perindopril arginine, perindopril arginine + amlodipine or indapamide + perindopril arginine +amlodipine<br>* Other names: Intensive BP control targeting SBP <120 mmHg.;|
| Active Comparator: Standard Control of Systolic Blood Pressure<br>Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg | Drug: Standard control of Systolic Blood Pressure (SBP)<br>* The same medications used in the Intensive BP arm will be used for the Standard BP arm.<br>* Other names: Standard control of SBP targeting SBP < 140 mmHg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure [ Time Frame: From randomization; for approximately a median of 3.5 years ] | Time to first event of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure | From randomization; for approximately a median of 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke [ Time Frame: From randomization; for approximately a median of 3.5 years ] | Time to first event of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke | From randomization; for approximately a median of 3.5 years | 
| Time to total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure [ Time Frame: From randomization; for approximately a median of 3.5 years ] | Time to first event of total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure | From randomization; for approximately a median of 3.5 years | 
| Time to non-fatal MI, non-fatal stroke, or total death | Time to non-fatal MI, non-fatal stroke or total death. | From randomization; for approximately a median of 3.5 years | 
| Time to Death | Time to all cause death | From randomization; for approximately a median of 3.5 years | 
| Time to Renal Death | Time to death from renal causes | From randomization; for approximately a median of 3.5 years | 
| Time to Renal Outcome | Time to Renal Outcome, defined as a 50% reduction in the glomerular filtration rate (GRF) associated with a final GFR of < 60 mL/min/1.73m2 in patients without chronic kidney disease (GFR 60-90 mL/min/1.73m2) at baseline. In those patients with chronic kidney disease (<60 mL/min/1.73m2) at baseline, the renal outcome will be defined as a 50% reduction in GFR or progression of renal disease to stage IV, requiring dialysis or kidney transplantation. | From randomization; for approximately a median of 3.5 years | 
| Time to Cardiovascular Death | Time to death from cardiovascular causes | From randomization; for approximately a median of 3.5 years | 
| Time to Stroke | Time to stroke | From randomization; for approximately a median of 3.5 years | 
| Time to Hemorrhagic Stroke | Time to hemorrhagic stroke | From randomization; for approximately a median of 3.5 years | 
| Time to Ischemic Stroke | Time to ischemic stroke | From randomization; for approximately a median of 3.5 years | 
| Time to Unclassified Stroke | Time to unclassified stroke | From randomization; for approximately a median of 3.5 years | 
| Time to Transient Ischemic Attack (TIA) | Time to Transient Ischemic Attack (TIA) | From randomization; for approximately a median of 3.5 years | 
| Time to Myocardial Infarction (MI) | Time to myocardial infarction (MI) | From randomization; for approximately a median of 3.5 years | 
| Time to Hospitalization due to Heart Failure | Time to hospitalization due to heart failure | From randomization; for approximately a median of 3.5 years | 
| Time to Hospitalization due to Unstable Angina | Time to Hospitalization due to unstable angina | From randomization; for approximately a median of 3.5 years | 
| Time to a Composite Outcome of Mild Cognitive Impairment or Probable All Cause Dementia | Occurrence of mild cognitive impairment or probable all-cause dementia | From randomization; for approximately a median of 3.5 years | 
| Time to Mild Cognitive Impairment | Time to Mild Cognitive Impairment | From randomization; for approximately a median of 3.5 years | 
| Time to All-Cause Probable Dementia | Time to all-cause probable dementia | From randomization; for approximately a median of 3.5 years |