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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Vascular Diseases; Ischemic Stroke; Cognitive Impairment; Blood Pressure
• Intervention / Treatment: Drug: Standard control of Systolic Blood Pressure (SBP); Drug: Intensive Control of Systolic Blood Pressure (SBP)

• Study Type: Interventional
• Enrollment (Actual): 4369
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Botucatu, Brazil, 18618-686
    • UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
  • Rio de Janeiro, Brazil, 20551-030
    • Hospital Universitario Pedro Ernesto - UERJ
  • São Paulo, Brazil, (11) 2661-0000
    • Hospital das Clinicas da FMUSP
  • São Paulo, Brazil, 04012-909
    • Instituto Dante Pazzanese de Cardiologia
  • São Paulo, Brazil, 04037-002
    • Hospital Sao Paulo
  • São Paulo, Brazil, 05403-900
    • InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
  • Acre
    • Rio Branco, Acre, Brazil
      • Clínica Silvestre Sante
  • Alagoas
    • Maceió, Alagoas, Brazil
      • Centro de Pesquisas Clinicas (Centro Universitário Cesmac / Hospital do Coração de Alagoas)
  • Bahia
    • Salvador, Bahia, Brazil, 40110-060
      • Hospital Universitario Professor Edgard Santos
    • Salvador, Bahia, Brazil, 40323-010
      • Hospital Ana Nery
  • Ceará
    • Fortaleza, Ceará, Brazil, 60175-295
      • Hospital Geral de Fortaleza
    • Fortaleza, Ceará, Brazil, 60430-372
      • Universidade Federal do Ceará / Hospital Universitário Walter Cantídio
  • DF
    • Brasilia, DF, Brazil, 70335900
      • Instituto Hospitalar de Base Do Distrito Federal
  • Goiás
    • Goiânia, Goiás, Brazil, 74690-900
      • Universidade Federal de Goias
  • Mato Grosso Do Sul
    • Campo Grande, Mato Grosso Do Sul, Brazil, 79080-190
      • Hospital Universitário Maria Aparecida Pedrossian - UFMS
  • Paraná
    • Curitiba, Paraná, Brazil, 82590-300
      • Flumignano Instituto de Medicina
  • Pernambuco
    • Recife, Pernambuco, Brazil, 74970-240
      • PROCAPE-Pronto Socorro Cardiológico de PE Prof. Luiz Tavares
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-000
      • Hospital Moinho de Ventos
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Hospital de Clinicas de Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • SP
    • São Paulo, SP, Brazil, 01221-020
      • Irmandade Da Santa Casa De Misericordia De Sao Paulo
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88015-270
      • Hospital Governador Celso Ramos
    • Joinville, Santa Catarina, Brazil, 89202-165
      • Clinica Neurologica e Neurocirurgica de Joinville Ltda
    • Joinville, Santa Catarina, Brazil
      • CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
  • São Paulo
    • Bragança Paulista, São Paulo, Brazil, 12916-542
      • Hospital Univ. São Francisco de Assis na Providencia de Deus
    • Campinas, São Paulo, Brazil, 13083-888
      • Universidade Estadual de Campinas - Hospital de Clínicas
    • Matão, São Paulo, Brazil, 15990-060
      • Hospital Carlos Fernando Malzoni
    • Ribeirão Preto, São Paulo, Brazil, 14015-010
      • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
    • São José Do Rio Preto, São Paulo, Brazil, 15090-365
      • Clínica Vilela e Martin
    • São José Do Rio Preto, São Paulo, Brazil, 150900000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive Control of Systolic Blood Pressure (SBP); 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); 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; Other Names: Intensive BP control targeting SBP <120 mmHg.
Active Comparator: Standard Control of Systolic Blood Pressure; Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg	Drug: Standard control of Systolic Blood Pressure (SBP); The same medications used in the Intensive BP arm will be used for the Standard BP arm.; Other Names: Standard control of SBP targeting SBP < 140 mmHg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Ministry of Health, Brazil
• Investigators: Study Director: Otavio Berwanger, MD, PhD, Hospital Israelita Albert Einstein

Publications and helpful links

General Publications

• 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. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Ischemic Stroke
• Other Study ID Numbers: OPTIMAL STROKE Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No