Optimal Blood Pressure for the prevenTIon of Major vAscuLar Events in Patients With DIABETES Mellitus (OPTIMAL-DIABETES)

Large-Scale Randomized Clinical Trial Assessing Intensive Blood Pressure Control for Reduction of Major Cardiovascular Events in Patients With Diabetes Mellitus (OPTIMAL-DIABETES)

High blood pressure (BP) is a major public health concern, especially in low and middle income countries. High BP is a highly prevalent condition, and it is usually associated with diabetes mellitus. Both high BP and diabetes are risk factors for major cardiovascular events including cardiovascular death, acute myocardial infarction, stroke, unstable angina and heart failure. In addition, high BP is also related to cognitive decline. The OPTIMAL-DIABETES trial consists of a two-arm, multicenter, randomized clinical trial designed to test whether a lower systolic blood pressure (SBP) target will reduce the occurrence of major cardiovascular events in diabetic patients compared to the standard SBP target.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Diabetes Mellitus; Cognitive Impairment; High 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): 9476
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20551-030
    • Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro
  • São Paulo, Brazil, 05403-000
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • São Paulo, Brazil
    • Instituto Dante Pazzanese de Cardiologia
  • São Paulo, Brazil
    • Irmandade Da Santa Casa De Misericordia De Sao Paulo
  • São Paulo, Brazil, 05403-000
    • Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • São Paulo, Brazil, 04025-010
    • Clínica de Metabologia e Hipertensão da Universidade Federal de São Paulo
  • São Paulo, Brazil
    • Real e Benemérita Associação Portuguesa de Beneficência/SP
  • Alagoas
    • Maceió, Alagoas, Brazil, 57051-160
      • Centro de Pesquisas Clínicas Dr Marco Mota
  • Ceará
    • Fortaleza, Ceará, Brazil
      • Instituto de Estudos E Pesquisas Clinicas Do Ceara
    • Fortaleza, Ceará, Brazil, 60430-350
      • Centro de Pesquisas em Diabetes e Doenças Endócrino-metabólicas
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29043-260
      • Hospital Universitario Cassiano Antonio de Moraes
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40323-010
      • Hospital Ana Nery
  • Federal District
    • Brasília, Federal District, Brazil, 70330-150
      • Instituto Hospital de Base
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • Universidade Federal de Goias
    • Goiânia, Goiás, Brazil, 90020-090
      • NS Clínica de Diabetes e Endocrinologia Ltda
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
    • Poços de Caldas, Minas Gerais, Brazil, 37710-005
      • Centro de Pesquisa do Hospital Santa Lúcia
  • Paraná
    • Curitiba, Paraná, Brazil
      • Medicina Nuclear Alto da XV
  • Pará
    • Belém, Pará, Brazil
      • Hospital Universitário João de Barros Barreto - UFPA
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50100-060
      • Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas Da Pucrs
  • Sergipe
    • Aracaju, Sergipe, Brazil, 49055-530
      • Centro de Pesquisa Clínica do Coração
  • São Paulo
    • Campinas, São Paulo, Brazil, 13073-350
      • Centro de Endocrinologia Geloneze
    • Campinas, São Paulo, Brazil
      • Universidade Estadual de Campinas - UNICAMP
    • Indaiatuba, São Paulo, Brazil
      • Indacor Servicos Medicos Ltda
    • Ribeirão Preto, São Paulo, Brazil, 14048-900
      • Hospital Das Clinicas Da Faculdade De Medicina De Ribeirao Preto da Universidade de Sao Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Centro Integrado de Pesquisas
    • São José do Rio Preto, São Paulo, Brazil, 15090-365
      • Clínica Vilela & Martin
    • São José do Rio Preto, São Paulo, Brazil, 15091-330
      • Instituto de Cardiologia e Endocrinologia Rio Preto Ltda
    • Votuporanga, São Paulo, Brazil
      • Santa Casa de Misericórdia de Votuporanga
    • Votuporanga, São Paulo, Brazil, 15505-189
      • Clínica Cardiológica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Systolic Blood Pressure (SBP) between 130 and 180 mm Hg:

  • 130 to 150 mm Hg (if on 0-4 medications)
  • 130 to 160 mm Hg (if on 0-3 medications)
  • 130 to 170 mm Hg (if on 0-2 medications)
  • 130 to 180 mm Hg (if on 0-1 medications)
• Type 2 diabetes

• To be considered as having a high cardiovascular risk, including AT LEAST ONE of the following factors:

  1. Established cardiovascular disease (CVD), including:

     • Coronary artery disease: previous myocardial infarction, previous acute coronary syndrome, previous percutaneous coronary intervention, previous coronary artery bypass graft surgery, or at least 50% stenosis in a main coronary artery associated with typical angina pectoris; or
     • Cerebrovascular disease: previous stroke (except those events caused by intracranial aneurysm or arteriovenous malformation) or previous transient ischemic attack (TIA), stable for at least 2 weeks preceding inclusion in the study; or
     • Carotid artery disease: previous carotid endarterectomy, previous percutaneous intervention with carotid stent implantation, or stenosis of at least 50% in a carotid shown by the Doppler ultrasonography, CT angiography or MR angiography; or
     • Peripheral artery disease: prior surgical or percutaneous revascularization of a peripheral artery, limb amputation due to vascular cause, abdominal aortic aneurysm ≥ 5 cm (with or without prior surgical or percutaneous repair), or stenosis of at least 50% in a peripheral artery associated to intermittent claudication.

  2. Subclinical CVD, including:

     • Coronary calcium score ≥ 300 Agatston units; or
     • Ankle-brachial index ≤ 0.90 in the last two years; or
     • Left ventricular hypertrophy on the electrocardiogram, echocardiogram or other cardiac imaging exam in the last two years.

  3. Chronic kidney disease (CKD):

     ▪ Definition of CKD: glomerular filtration rate (GFR) between 20 and 59 ml/min/1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

  4. Additional cardiovascular risk factors, including:

     • Active smoking: Defined as regular use of cigarettes or other tobacco products, such as cigars and pipe, in the last six months;
     • Dyslipidemia: Defined as LDL cholesterol > 70 mg/dL or non-HDL cholesterol > 100 mg/dL in patients with previous CVD; or LDL cholesterol > 100 mg/dL or non-HDL cholesterol > 130 mg/dL in patients without previous CVD; or Triglycerides > 200 mg/dL or HDL < 40 mg/dL regardless of treatment; or use of statins or other lipid lowering medication; or
     • Age ≥ 75 years

Exclusion Criteria:

• Refusal to provide written informed consent
• Body mass index > 45 kg/m2
• Known secondary cause of hypertension
• Severe renal dysfunction with GFR < 20 mL/min/1.73m2 calculated by the CKD-EPI equation
• Angina at rest Class IV Canadian Cardiovascular Society (CCS)
• Acute coronary syndrome in the last six months
• Symptomatic heart failure Class IV New York Heart Association (NYHA) or ejection fraction < 35% on Doppler echocardiography in the last six months

• Factors that at the research team´s judgment may limit adherence to the intervention and study protocol, including, but not limited to, the following examples:

  • Recent history of alcohol and illicit drug abuse
  • Psychiatric comorbidities (severe depression, schizophrenia, psychosis, etc.)
  • History of poor medication adherence and attendance to consultations
  • Any plans to move the city of residence in the next four years
  • Any plans to leave the city of residence for more than three months in the next few years
  • Living in the same residence of another patient previously included in this study
• Patients currently enrolled in another study for CVD prevention, including those evaluating pharmacological and non-pharmacological interventions
• Pregnancy or breastfeeding

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 (ARB), thiazide-type diuretics, and calcium channel blockers (CCB) 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 mm Hg
Active Comparator: Standard Control of Systolic Blood Pressure (SBP); 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 mm Hg

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 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 to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke	Time to first event of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke	From randomization to 48 months
Time to total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure	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 to 48 months
Time to Death	Time to all cause death	From randomization to 48 months
Time to Cardiovascular Death	Time to death from cardiovascular causes	From randomization to 48 months
Time to Renal Death	Time to death from renal causes	From randomization to 48 months
Time to Myocardial Infarction (MI)	Time to myocardial infarction (MI)	From randomization to 48 months
Time to Stroke	Time to stroke	From randomization to 48 months
Time to Ischemic Stroke	Time to ischemic stroke	Follow-up of 48 months
Time to Hemorrhagic Stroke	Time to hemorrhagic stroke	From randomization to 48 months
Time to Undetermined type of Stroke	Time to Undetermined type of Stroke	From randomization to 48 months
Time to Transient Ischemic Attack (TIA)	Time to transient ischemic attack (TIA)	From randomization to 48 months
Time to Hospitalization for Unstable Angina	Time to Hospitalization for unstable angina	From randomization to 48 months
Time to Hospitalization for Heart Failure	Time to hospitalization for heart failure	From randomization to 48 months
Time to Renal Outcome	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	From randomization to 48 months
Time to Mild Cognitive Impairment	Time to Mild Cognitive Impairment	From randomization to 48 months
Time to Mild Cognitive Impairment or All-Cause Probable Dementia	Time to mild cognitive impairment or all-cause probable dementia	From randomization to 48 months
Time to All-Cause Probable Dementia	Time to all-cause probable dementia	From randomization to 48 months
Cognitive Impairment	Decline in the Montreal Cognitive Assessment (MoCA) score calculated as the difference between initial and last assessments	From randomization to 48 months

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 8, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Glucose Metabolism Disorders; Cognition Disorders; Nutritional and Metabolic Diseases; Hypertension; Cognitive Dysfunction; Cardiovascular Diseases; Diabetes Mellitus
• Other Study ID Numbers: OPTIMAL-DIABETES Trial; 02795218.8.1001.0071 (Other Identifier: Plataforma Brasil (CAAE #)); 25000.028978/2018-02 (Other Grant/Funding Number: Ministry of Health, Brazil (NUP#))

Drug and device information, study documents

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