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

NCT ID: NCT04040634

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 9479 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-08
• Study Completion Date: 2025-12-31

Brief Summary

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.

Conditions

Cognitive Impairment; Diabetes Mellitus; High Blood Pressure; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intensive Control of Systolic Blood Pressure (SBP)

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

Group Type: EXPERIMENTAL

Intensive Control of Systolic Blood Pressure (SBP)

Intervention Type: DRUG

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

Standard Control of Systolic Blood Pressure (SBP)

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

Group Type: ACTIVE_COMPARATOR

Standard control of Systolic Blood Pressure (SBP)

Intervention Type: DRUG

The same medications used in the Intensive BP arm will be used for the Standard BP arm.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Intensive BP control targeting SBP <120 mm Hg; Standard control of SBP targeting SBP < 140 mm Hg

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Otavio Berwanger, MD, PhD

Role: STUDY_DIRECTOR

Hospital Israelita Albert Einstein

Locations

Centro de Pesquisas Clínicas Dr Marco Mota

Maceió, Alagoas, Brazil

Instituto de Estudos E Pesquisas Clinicas Do Ceara

Fortaleza, Ceará, Brazil

Hospital Universitário Cassiano Antonio de Moraes

Vitória, Espírito Santo, Brazil

Centro de Pesquisas em Diabetes e Doenças Endocrino-Metabólicas

Fortaleza, Estado de Bahia, Brazil

Hospital Ana Nery

Salvador, Estado de Bahia, Brazil

Instituto Hospital de Base

Brasília, Federal District, Brazil

Universidade Federal de Goiás

Goiânia, Goiás, Brazil

NS Clínica de Diabetes e Endocrinologia Ltda

Goiânia, Goiás, Brazil

Hospital das Clinicas da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Centro de Pesquisa do Hospital Santa Lúcia

Poços de Caldas, Minas Gerais, Brazil

Medicina Nuclear Alto da XV

Curitiba, Paraná, Brazil

Hospital Universitário João de Barros Barreto - UFPA

Belém, Pará, Brazil

Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva

Recife, Pernambuco, Brazil

Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, Brazil

Centro de Endocrinologia Geloneze

Campinas, São Paulo, Brazil

Universidade Estadual de Campinas - UNICAMP

Campinas, São Paulo, Brazil

Indacor Servicos Medicos Ltda

Indaiatuba, São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, Brazil

Centro Integrado de Pesquisas

São José do Rio Preto, São Paulo, Brazil

Clínica Vilela & Martin

São José do Rio Preto, São Paulo, Brazil

Instituto de Cardiologia e Endocrinologia Rio Preto Ltda

São José do Rio Preto, São Paulo, Brazil

Clínica de Metabologia e Hipertensão da Universidade Federal de São Paulo

São Paulo, São Paulo, Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, Brazil

Irmandade Da Santa Casa de Misericordia de Sao Paulo

São Paulo, São Paulo, Brazil

Real e Benemérita Associação Portuguesa de Beneficência/SP

São Paulo, São Paulo, Brazil

Clínica Cardiológica

Votuporanga, São Paulo, Brazil

Santa Casa de Misericordia de Votuporanga

Votuporanga, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 36398903 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32905623 (View on PubMed)

Other Identifiers

02795218.8.1001.0071

Identifier Type: OTHER

Identifier Source: secondary_id

25000.028978/2018-02

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OPTIMAL-DIABETES Trial

Identifier Type: -

Identifier Source: org_study_id