Blood Pressure, Cognitive Impairment, Ischemic Stroke, Vascular Diseases
Conditions
Brief summary
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.
Interventions
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
The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Sponsors
Hospital Israelita Albert Einstein
Ministry of Health, Brazil
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 mean of 3.5 years ] | From randomization; for approximately a mean 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke [ Time Frame: From randomization; for approximately a mean of 3.5 years ] | From randomization; for approximately a mean of 3.5 years | Time to first event of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke |
| 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 mean of 3.5 years ] | From randomization; for approximately a mean 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 |
| Time to Death | From randomization; for approximately a mean of 3.5 years | Time to all cause death |
| Time to Stroke | From randomization; for approximately a mean of 3.5 years | Time to stroke |
| Time to Hemorrhagic Stroke | From randomization; for approximately a mean of 3.5 years | Time to hemorrhagic stroke |
| Time to Ischemic Stroke | From randomization; for approximately a mean of 3.5 years | Time to ischemic stroke |
| Time to Unclassified Stroke | From randomization; for approximately a mean of 3.5 years | Time to unclassified stroke |
| Time to Transient Ischemic Attack (TIA) | From randomization; for approximately a mean of 3.5 years | Time to Transient Ischemic Attack (TIA) |
| Time to Renal Death | From randomization; for approximately a mean of 3.5 years | Time to death from renal causes |
| Time to Renal Outcome | From randomization; for approximately a mean of 3.5 years | Time to Renal Outcome, defined as a ≥50% reduction in the glomerular filtration rate (GFR) from baseline (excluding acute reversible causes) or progression to end-stage renal disease, which is defined as a GFR \< 15 mL/min/1.73m² (excluding reversible causes) or the need for dialysis (hemodialysis or peritoneal dialysis for at least 30 days) or kidney transplantation. |
| Time to Cardiovascular Death | From randomization; for approximately a mean of 3.5 years | Time to death from cardiovascular causes |
| Time to Myocardial Infarction (MI) | From randomization; for approximately a mean of 3.5 years | Time to myocardial infarction (MI) |
| Time to Hospitalization due to Heart Failure | From randomization; for approximately a mean of 3.5 years | Time to hospitalization due to heart failure |
| Time to Hospitalization due to Unstable Angina | From randomization; for approximately a mean of 3.5 years | Time to Hospitalization due to unstable angina |
| Cognitive Impairment | From initial assessment, for approximately a mean of 3.5 years | Decline in the Montreal Cognitive Assessment (MoCA) score calculated as the difference between initial assessment and last visit scores |
| Time to a Composite Outcome of Mild Cognitive Impairment or Probable All Cause Dementia | From initial assessment, for approximately a mean of 3.5 years | Occurrence of mild cognitive impairment or probable all-cause dementia |
| Time to Mild Cognitive Impairment | From initial assessment, for approximately a mean of 3.5 years | Time to Mild Cognitive Impairment |
| Time to All-Cause Probable Dementia | From initial assessment, for approximately a mean of 3.5 years | Time to all-cause probable dementia |
Countries
Brazil
Contacts
STUDY_DIRECTOROtavio Berwanger, MD, PhD
Hospital Israelita Albert Einstein
Outcome results
None listed