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

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04040634
• Other study ID #: OPTIMAL-DIABETES Trial
• Secondary ID: 02795218.8.1001.
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 8, 2019
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9479
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cognitive Impairment
• Diabetes Mellitus
• High Blood Pressure
• Hypertension

Intervention

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
• Standard control of Systolic Blood Pressure (SBP)
The same medications used in the Intensive BP arm will be used for the Standard BP arm.

Locations

Country	Name	City	State
Brazil	Centro de Pesquisa Clínica do Coração	Aracaju	Sergipe
Brazil	Hospital Universitário João de Barros Barreto - UFPA	Belém	Pará
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 Endocrinologia Geloneze	Campinas	São Paulo
Brazil	Universidade Estadual de Campinas - UNICAMP	Campinas	São Paulo
Brazil	Medicina Nuclear Alto da XV	Curitiba	Paraná
Brazil	Centro de Pesquisas em Diabetes e Doenças Endocrino-Metabólicas	Fortaleza	Bahia
Brazil	Instituto de Estudos E Pesquisas Clinicas Do Ceara	Fortaleza	Ceará
Brazil	NS Clínica de Diabetes e Endocrinologia Ltda	Goiânia	Goiás
Brazil	Universidade Federal de Goiás	Goiânia	Goiás
Brazil	Indacor Servicos Medicos Ltda	Indaiatuba	São Paulo
Brazil	Centro de Pesquisas Clínicas Dr Marco Mota	Maceió	Alagoas
Brazil	Centro de Pesquisa do Hospital Santa Lúcia	Poços De Caldas	Minas Gerais
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	Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva	Recife	Pernambuco
Brazil	Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo
Brazil	Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro	Rio de Janeiro
Brazil	Hospital Ana Nery	Salvador	Bahia
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
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Instituto Dante Pazzanese de Cardiologia	São Paulo
Brazil	Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Irmandade Da Santa Casa de Misericordia de Sao Paulo	São Paulo
Brazil	Real e Benemérita Associação Portuguesa de Beneficência/SP	São Paulo
Brazil	Hospital Universitário Cassiano Antonio de Moraes	Vitória	Espirito Santo
Brazil	Clínica Cardiológica	Votuporanga	São Paulo
Brazil	Santa Casa de Misericordia de Votuporanga	Votuporanga	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	Ministry of Health, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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; for approximately a median of 3.5 years
Secondary	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; for approximately a median of 3.5 years
Secondary	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; for approximately a median of 3.5 years
Secondary	Time to Death	Time to all cause death	From randomization; for approximately a median of 3.5 years
Secondary	Time to Cardiovascular Death	Time to death from cardiovascular causes	From randomization; for approximately a median of 3.5 years
Secondary	Time to Renal Death	Time to death from renal causes	From randomization; for approximately a median of 3.5 years
Secondary	Time to Myocardial Infarction (MI)	Time to myocardial infarction (MI)	From randomization; for approximately a median of 3.5 years
Secondary	Time to Stroke	Time to stroke	From randomization; for approximately a median of 3.5 years
Secondary	Time to Ischemic Stroke	Time to ischemic stroke	From randomization; for approximately a median of 3.5 years
Secondary	Time to Hemorrhagic Stroke	Time to hemorrhagic stroke	From randomization; for approximately a median of 3.5 years
Secondary	Time to Undetermined type of Stroke	Time to Undetermined type of Stroke	From randomization; for approximately a median of 3.5 years
Secondary	Time to Transient Ischemic Attack (TIA)	Time to transient ischemic attack (TIA)	From randomization; for approximately a median of 3.5 years
Secondary	Time to Hospitalization for Unstable Angina	Time to Hospitalization for unstable angina	From randomization; for approximately a median of 3.5 years
Secondary	Time to Hospitalization for Heart Failure	Time to hospitalization for heart failure	From randomization; for approximately a median of 3.5 years
Secondary	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
Secondary	Time to Mild Cognitive Impairment	Time to Mild Cognitive Impairment	From randomization; for approximately a median of 3.5 years
Secondary	Time to Mild Cognitive Impairment or All-Cause Probable Dementia	Time to mild cognitive impairment or all-cause probable dementia	From randomization; for approximately a median of 3.5 years
Secondary	Time to All-Cause Probable Dementia	Time to all-cause probable dementia	From randomization; for approximately a median of 3.5 years