Clinical trial NCT04040634: Optimal Blood Pressure for the prevenTIon of Major vAscuLar Events in Patients With DIABETES Mellitus (OPTIMAL-DIABETES)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Diabetes Mellitus
High Blood Pressure
Cardiovascular Diseases
Cognitive Impairment
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
First posted: 2019-08-01
Enrollment: 9479
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time to cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure
timeFrame: From randomization; for approximately a median of 3.5 years
Secondary outcomes:
measure: Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Death
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Cardiovascular Death
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Renal Death
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Myocardial Infarction (MI)
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Stroke
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Ischemic Stroke
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Hemorrhagic Stroke
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Undetermined type of Stroke
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Transient Ischemic Attack (TIA)
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Hospitalization for Unstable Angina
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Hospitalization for Heart Failure
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Renal Outcome
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Mild Cognitive Impairment
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to Mild Cognitive Impairment or All-Cause Probable Dementia
timeFrame: From randomization; for approximately a median of 3.5 years
measure: Time to All-Cause Probable Dementia
timeFrame: From randomization; for approximately a median of 3.5 years
Other outcomes:
Locations:
city: Maceió
country: Brazil
facility: Centro de Pesquisas Clínicas Dr Marco Mota
state: Alagoas
city: Fortaleza
country: Brazil
facility: Centro de Pesquisas em Diabetes e Doenças Endocrino-Metabólicas
state: Bahia
city: Salvador
country: Brazil
facility: Hospital Ana Nery
state: Bahia
city: Fortaleza
country: Brazil
facility: Instituto de Estudos E Pesquisas Clinicas Do Ceara
state: Ceará
city: Brasília
country: Brazil
facility: Instituto Hospital de Base
state: Distrito Federal
city: Vitória
country: Brazil
facility: Hospital Universitário Cassiano Antonio de Moraes
state: Espirito Santo
city: Goiânia
country: Brazil
facility: Universidade Federal de Goiás
state: Goiás
city: Goiânia
country: Brazil
facility: NS Clínica de Diabetes e Endocrinologia Ltda
state: Goiás
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Minas Gerais
state: Minas Gerais
city: Poços De Caldas
country: Brazil
facility: Centro de Pesquisa do Hospital Santa Lúcia
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Medicina Nuclear Alto da XV
state: Paraná
city: Belém
country: Brazil
facility: Hospital Universitário João de Barros Barreto - UFPA
state: Pará
city: Recife
country: Brazil
facility: Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clínica do Coração
state: Sergipe
city: Campinas
country: Brazil
facility: Centro de Endocrinologia Geloneze
state: São Paulo
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas - UNICAMP
state: São Paulo
city: Indaiatuba
country: Brazil
facility: Indacor Servicos Medicos Ltda
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Centro Integrado de Pesquisas
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Clínica Vilela & Martin
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Instituto de Cardiologia e Endocrinologia Rio Preto Ltda
state: São Paulo
city: Votuporanga
country: Brazil
facility: Clínica Cardiológica
state: São Paulo
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericordia de Votuporanga
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro
city: São Paulo
country: Brazil
facility: Clínica de Metabologia e Hipertensão da Universidade Federal de São Paulo
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: São Paulo
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Sao Paulo
city: São Paulo
country: Brazil
facility: Real e Benemérita Associação Portuguesa de Beneficência/SP
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Otavio Berwanger, MD, PhD
role: STUDY_DIRECTOR
References:
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.
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.