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

Not Applicable

Active, not recruiting

• Conditions: High Blood Pressure; Diabetes Mellitus; Cardiovascular Diseases; Cognitive Impairment
• Interventions: Drug: Intensive Control of Systolic Blood Pressure (SBP); Drug: Standard control of Systolic Blood Pressure (SBP)

• Registration Number: NCT04040634
• Lead Sponsor: Hospital Israelita Albert Einstein

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-30
• Study First Submitted QC: 2019-07-30
• Study First Posted: 2019-08-01
• Study Start: 2019-08-08
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-02
• Last Update Posted: 2024-01-03
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 9479

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive Control of Systolic Blood Pressure (SBP)	Intensive Control of Systolic Blood Pressure (SBP)	Participants randomized into the Intensive Blood Pressure arm will have a goal of SBP \<120 mm Hg.
Standard Control of Systolic Blood Pressure (SBP)	Standard control of Systolic Blood Pressure (SBP)	Participants randomized into the Standard arm will have a goal of SBP \<140 mm Hg.

Primary Outcome Measures

Name	Time	Method
Time to 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	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

Name	Time	Method
Time to All-Cause Probable Dementia	From randomization; for approximately a median of 3.5 years	Time to all-cause probable dementia
Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke	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 Renal Death	From randomization; for approximately a median of 3.5 years	Time to death from renal causes
Time to Myocardial Infarction (MI)	From randomization; for approximately a median of 3.5 years	Time to myocardial infarction (MI)
Time to Undetermined type of Stroke	From randomization; for approximately a median of 3.5 years	Time to Undetermined type of Stroke
Time to Transient Ischemic Attack (TIA)	From randomization; for approximately a median of 3.5 years	Time to transient ischemic attack (TIA)
Time to Death	From randomization; for approximately a median of 3.5 years	Time to all cause death
Time to Hospitalization for Unstable Angina	From randomization; for approximately a median of 3.5 years	Time to Hospitalization for unstable angina
Time to Mild Cognitive Impairment	From randomization; for approximately a median of 3.5 years	Time to Mild Cognitive Impairment
Time to Cardiovascular Death	From randomization; for approximately a median of 3.5 years	Time to death from cardiovascular causes
Time to Ischemic Stroke	From randomization; for approximately a median of 3.5 years	Time to ischemic stroke
Time to Hospitalization for Heart Failure	From randomization; for approximately a median of 3.5 years	Time to hospitalization for heart failure
Time to Stroke	From randomization; for approximately a median of 3.5 years	Time to stroke
Time to 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 first event of total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure
Time to Hemorrhagic Stroke	From randomization; for approximately a median of 3.5 years	Time to hemorrhagic stroke
Time to Renal Outcome	From randomization; for approximately a median of 3.5 years	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 Mild Cognitive Impairment or All-Cause Probable Dementia	From randomization; for approximately a median of 3.5 years	Time to mild cognitive impairment or all-cause probable dementia

Trial Locations

Locations (32)

Real e Benemérita Associação Portuguesa de Beneficência/SP; 🇧🇷 São Paulo, Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; 🇧🇷 São Paulo, Brazil

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; 🇧🇷 São Paulo, Brazil

Hospital Universitário João de Barros Barreto - UFPA; 🇧🇷 Belém, Pará, Brazil

Universidade Federal de Goiás; 🇧🇷 Goiânia, Goiás, Brazil

Hospital Universitário Cassiano Antonio de Moraes; 🇧🇷 Vitória, Espirito Santo, Brazil

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Instituto de Estudos E Pesquisas Clinicas Do Ceara; 🇧🇷 Fortaleza, Ceará, Brazil

Indacor Servicos Medicos Ltda; 🇧🇷 Indaiatuba, São Paulo, Brazil

Medicina Nuclear Alto da XV; 🇧🇷 Curitiba, Paraná, Brazil

Santa Casa de Misericordia de Votuporanga; 🇧🇷 Votuporanga, São Paulo, Brazil

Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro; 🇧🇷 Rio de Janeiro, Brazil

NS Clínica de Diabetes e Endocrinologia Ltda; 🇧🇷 Goiânia, Goiás, Brazil

Centro de Endocrinologia Geloneze; 🇧🇷 Campinas, São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; 🇧🇷 Ribeirão Preto, São Paulo, Brazil

Clínica Vilela & Martin; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Clínica de Metabologia e Hipertensão da Universidade Federal de São Paulo; 🇧🇷 São Paulo, Brazil

Instituto de Cardiologia e Endocrinologia Rio Preto Ltda; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, Brazil

Centro de Pesquisas em Diabetes e Doenças Endocrino-Metabólicas; 🇧🇷 Fortaleza, Bahia, Brazil

Hospital Ana Nery; 🇧🇷 Salvador, Bahia, Brazil

Centro de Pesquisas Clínicas Dr Marco Mota; 🇧🇷 Maceió, Alagoas, Brazil

Hospital das Clinicas da Universidade Federal de Minas Gerais; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Instituto Hospital de Base; 🇧🇷 Brasília, Distrito Federal, Brazil

Centro de Pesquisa do Hospital Santa Lúcia; 🇧🇷 Poços De Caldas, Minas Gerais, Brazil

Hospital São Lucas da PUCRS; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva; 🇧🇷 Recife, Pernambuco, Brazil

Universidade Estadual de Campinas - UNICAMP; 🇧🇷 Campinas, São Paulo, Brazil

Centro Integrado de Pesquisas; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

Clínica Cardiológica; 🇧🇷 Votuporanga, São Paulo, Brazil

Centro de Pesquisa Clínica do Coração; 🇧🇷 Aracaju, Sergipe, Brazil

Irmandade Da Santa Casa de Misericordia de Sao Paulo; 🇧🇷 São Paulo, Brazil