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

Primary Purpose

Ischemic Stroke, Blood Pressure, Cognitive Impairment

Status
Active
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Intensive Control of Systolic Blood Pressure (SBP)
Standard control of Systolic Blood Pressure (SBP)
Sponsored by
Hospital Israelita Albert Einstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Clínica Silvestre Santé
  • Centro de Pesquisas Clinicas (Centro Universitário Cesmac / Hospital do Coração de Alagoas)
  • Hospital Universitário Professor Edgard Santos
  • Hospital Ana Nery
  • Hospital Geral de Fortaleza
  • Universidade Federal do Ceará / Hospital Universitário Walter Cantídio
  • Instituto Hospitalar de Base Do Distrito Federal
  • Universidade Federal de Goias
  • Hospital Universitário Maria Aparecida Pedrossian - UFMS
  • Flumignano Instituto de Medicina
  • PROCAPE-Pronto Socorro Cardiológico de PE Prof. Luiz Tavares
  • Hospital Moinho de Ventos
  • Hospital de Clínicas de Porto Alegre
  • Hospital de Clínicas de Porto Alegre
  • Hospital Governador Celso Ramos
  • Clínica Neurológica e Neurocirurgica de Joinville LTDA
  • CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
  • Irmandade da Santa Casa de Misericórdia de São Paulo
  • Hospital Univ. São Francisco de Assis na Providencia de Deus
  • Universidade Estadual de Campinas - Hospital de Clínicas
  • Hospital Carlos Fernando Malzoni
  • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
  • Clínica Vilela e Martin
  • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
  • Hospital Universitário Pedro Ernesto - UERJ
  • Hospital das Clínicas da FMUSP
  • Instituto Dante Pazzanese de Cardiologia
  • Hospital São Paulo
  • InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intensive Control of Systolic Blood Pressure (SBP)

Standard Control of Systolic Blood Pressure

Arm Description

Participants randomized into the Intensive Blood Pressure arm will have a goal of SBP <120 mm Hg.

Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Time to non-fatal MI, non-fatal stroke, or total death
Time to non-fatal MI, non-fatal stroke or total death.
Time to Death
Time to all cause death
Time to Renal Death
Time to death from renal causes
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.
Time to Cardiovascular Death
Time to death from cardiovascular causes
Time to Stroke
Time to stroke
Time to Hemorrhagic Stroke
Time to hemorrhagic stroke
Time to Ischemic Stroke
Time to ischemic stroke
Time to Unclassified Stroke
Time to unclassified stroke
Time to Transient Ischemic Attack (TIA)
Time to Transient Ischemic Attack (TIA)
Time to Myocardial Infarction (MI)
Time to myocardial infarction (MI)
Time to Hospitalization due to Heart Failure
Time to hospitalization due to heart failure
Time to Hospitalization due to Unstable Angina
Time to Hospitalization due to unstable angina
Time to a Composite Outcome of Mild Cognitive Impairment or Probable All Cause Dementia
Occurrence of mild cognitive impairment or probable all-cause dementia
Time to Mild Cognitive Impairment
Time to Mild Cognitive Impairment
Time to All-Cause Probable Dementia
Time to all-cause probable dementia

Full Information

First Posted
July 26, 2019
Last Updated
May 15, 2023
Sponsor
Hospital Israelita Albert Einstein
Collaborators
Ministry of Health, Brazil
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1. Study Identification

Unique Protocol Identification Number
NCT04036409
Brief Title
Optimal Blood Pressure for the prevenTIon of Major vAscuLar Events in Stroke Patients
Acronym
OPTIMAL Stroke
Official Title
A Randomized Controlled Trial to Assess the Effect of Intensive Blood Pressure Control on Major Cardiovascular Events in Stroke Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 5, 2019 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Israelita Albert Einstein
Collaborators
Ministry of Health, Brazil

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Blood Pressure, Cognitive Impairment, Vascular Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
4369 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intensive Control of Systolic Blood Pressure (SBP)
Arm Type
Experimental
Arm Description
Participants randomized into the Intensive Blood Pressure arm will have a goal of SBP <120 mm Hg.
Arm Title
Standard Control of Systolic Blood Pressure
Arm Type
Active Comparator
Arm Description
Participants randomized into the Standard arm will have a goal of SBP <140 mm Hg
Intervention Type
Drug
Intervention Name(s)
Intensive Control of Systolic Blood Pressure (SBP)
Other Intervention Name(s)
Intensive BP control targeting SBP <120 mmHg.
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Standard control of Systolic Blood Pressure (SBP)
Other Intervention Name(s)
Standard control of SBP targeting SBP < 140 mmHg
Intervention Description
The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Primary Outcome Measure Information:
Title
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 ]
Description
Time to first event of 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
Secondary Outcome Measure Information:
Title
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 ]
Description
Time to first event of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke
Time Frame
From randomization; for approximately a median of 3.5 years
Title
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 ]
Description
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 Frame
From randomization; for approximately a median of 3.5 years
Title
Time to non-fatal MI, non-fatal stroke, or total death
Description
Time to non-fatal MI, non-fatal stroke or total death.
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Death
Description
Time to all cause death
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Renal Death
Description
Time to death from renal causes
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Renal Outcome
Description
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.
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Cardiovascular Death
Description
Time to death from cardiovascular causes
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Stroke
Description
Time to stroke
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Hemorrhagic Stroke
Description
Time to hemorrhagic stroke
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Ischemic Stroke
Description
Time to ischemic stroke
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Unclassified Stroke
Description
Time to unclassified stroke
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Transient Ischemic Attack (TIA)
Description
Time to Transient Ischemic Attack (TIA)
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Myocardial Infarction (MI)
Description
Time to myocardial infarction (MI)
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Hospitalization due to Heart Failure
Description
Time to hospitalization due to heart failure
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Hospitalization due to Unstable Angina
Description
Time to Hospitalization due to unstable angina
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to a Composite Outcome of Mild Cognitive Impairment or Probable All Cause Dementia
Description
Occurrence of mild cognitive impairment or probable all-cause dementia
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to Mild Cognitive Impairment
Description
Time to Mild Cognitive Impairment
Time Frame
From randomization; for approximately a median of 3.5 years
Title
Time to All-Cause Probable Dementia
Description
Time to all-cause probable dementia
Time Frame
From randomization; for approximately a median of 3.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Otavio Berwanger, MD, PhD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Director
Facility Information:
Facility Name
Clínica Silvestre Santé
City
Rio Branco
State/Province
Acre
Country
Brazil
Facility Name
Centro de Pesquisas Clinicas (Centro Universitário Cesmac / Hospital do Coração de Alagoas)
City
Maceió
State/Province
Alagoas
Country
Brazil
Facility Name
Hospital Universitário Professor Edgard Santos
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40110-060
Country
Brazil
Facility Name
Hospital Ana Nery
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40323-010
Country
Brazil
Facility Name
Hospital Geral de Fortaleza
City
Fortaleza
State/Province
Ceará
ZIP/Postal Code
60175-295
Country
Brazil
Facility Name
Universidade Federal do Ceará / Hospital Universitário Walter Cantídio
City
Fortaleza
State/Province
Ceará
ZIP/Postal Code
60430-372
Country
Brazil
Facility Name
Instituto Hospitalar de Base Do Distrito Federal
City
Brasilia
State/Province
DF
ZIP/Postal Code
70335900
Country
Brazil
Facility Name
Universidade Federal de Goias
City
Goiânia
State/Province
Goiás
ZIP/Postal Code
74690-900
Country
Brazil
Facility Name
Hospital Universitário Maria Aparecida Pedrossian - UFMS
City
Campo Grande
State/Province
Mato Grosso Do Sul
ZIP/Postal Code
79080-190
Country
Brazil
Facility Name
Flumignano Instituto de Medicina
City
Curitiba
State/Province
Paraná
ZIP/Postal Code
82590-300
Country
Brazil
Facility Name
PROCAPE-Pronto Socorro Cardiológico de PE Prof. Luiz Tavares
City
Recife
State/Province
Pernambuco
ZIP/Postal Code
74970-240
Country
Brazil
Facility Name
Hospital Moinho de Ventos
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-000
Country
Brazil
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-007
Country
Brazil
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Hospital Governador Celso Ramos
City
Florianópolis
State/Province
Santa Catarina
ZIP/Postal Code
88015-270
Country
Brazil
Facility Name
Clínica Neurológica e Neurocirurgica de Joinville LTDA
City
Joinville
State/Province
Santa Catarina
ZIP/Postal Code
89202-165
Country
Brazil
Facility Name
CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
City
Joinville
State/Province
Santa Catarina
Country
Brazil
Facility Name
Irmandade da Santa Casa de Misericórdia de São Paulo
City
São Paulo
State/Province
SP
ZIP/Postal Code
01221-020
Country
Brazil
Facility Name
Hospital Univ. São Francisco de Assis na Providencia de Deus
City
Bragança Paulista
State/Province
São Paulo
ZIP/Postal Code
12916-542
Country
Brazil
Facility Name
Universidade Estadual de Campinas - Hospital de Clínicas
City
Campinas
State/Province
São Paulo
ZIP/Postal Code
13083-888
Country
Brazil
Facility Name
Hospital Carlos Fernando Malzoni
City
Matão
State/Province
São Paulo
ZIP/Postal Code
15990-060
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
City
Ribeirão Preto
State/Province
São Paulo
ZIP/Postal Code
14015-010
Country
Brazil
Facility Name
Clínica Vilela e Martin
City
São José Do Rio Preto
State/Province
São Paulo
ZIP/Postal Code
15090-365
Country
Brazil
Facility Name
Fundação Faculdade Regional de Medicina de São José do Rio Preto
City
São José Do Rio Preto
State/Province
São Paulo
ZIP/Postal Code
150900000
Country
Brazil
Facility Name
UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
City
Botucatu
ZIP/Postal Code
18618-686
Country
Brazil
Facility Name
Hospital Universitário Pedro Ernesto - UERJ
City
Rio de Janeiro
ZIP/Postal Code
20551-030
Country
Brazil
Facility Name
Hospital das Clínicas da FMUSP
City
São Paulo
ZIP/Postal Code
(11) 2661-0000
Country
Brazil
Facility Name
Instituto Dante Pazzanese de Cardiologia
City
São Paulo
ZIP/Postal Code
04012-909
Country
Brazil
Facility Name
Hospital São Paulo
City
São Paulo
ZIP/Postal Code
04037-002
Country
Brazil
Facility Name
InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
City
São Paulo
ZIP/Postal Code
05403-900
Country
Brazil

12. IPD Sharing Statement

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
PubMed Identifier
32905623
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. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.
Results Reference
derived

Learn more about this trial

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

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