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

• Sponsor: Hospital Israelita Albert Einstein (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04040634
• Collaborator: Ministry of Health, Brazil (Other)
• Enrollment: 9,479
• Locations: 32
• Arms: 2
• Anticipated Duration (Months): 51.8
• Patients Per Site: 296.2
• Patients Per Site Per Month: 5.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus; High Blood Pressure; Cardiovascular Diseases; Cognitive Impairment	Drug: Intensive Control of Systolic Blood Pressure (SBP); Drug: Standard control of Systolic Blood Pressure (SBP)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 9479 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Aug 8, 2019
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

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.; 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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. Time to Death [From randomization; for approximately a median of 3.5 years]

   Time to all cause death

4. Time to Cardiovascular Death [From randomization; for approximately a median of 3.5 years]

   Time to death from cardiovascular causes

5. Time to Renal Death [From randomization; for approximately a median of 3.5 years]

   Time to death from renal causes

6. Time to Myocardial Infarction (MI) [From randomization; for approximately a median of 3.5 years]

   Time to myocardial infarction (MI)

7. Time to Stroke [From randomization; for approximately a median of 3.5 years]

   Time to stroke

8. Time to Ischemic Stroke [From randomization; for approximately a median of 3.5 years]

   Time to ischemic stroke

9. Time to Hemorrhagic Stroke [From randomization; for approximately a median of 3.5 years]

   Time to hemorrhagic stroke

10. Time to Undetermined type of Stroke [From randomization; for approximately a median of 3.5 years]

    Time to Undetermined type of Stroke

11. Time to Transient Ischemic Attack (TIA) [From randomization; for approximately a median of 3.5 years]

    Time to transient ischemic attack (TIA)

12. Time to Hospitalization for Unstable Angina [From randomization; for approximately a median of 3.5 years]

    Time to Hospitalization for unstable angina

13. Time to Hospitalization for Heart Failure [From randomization; for approximately a median of 3.5 years]

    Time to hospitalization for heart failure

14. 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.

15. Time to Mild Cognitive Impairment [From randomization; for approximately a median of 3.5 years]

    Time to Mild Cognitive Impairment

16. 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

17. Time to All-Cause Probable Dementia [From randomization; for approximately a median of 3.5 years]

    Time to all-cause probable dementia

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

1. 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).

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro de Pesquisas Clínicas Dr Marco Mota	Maceió	Alagoas	Brazil	57051-160
2	Centro de Pesquisas em Diabetes e Doenças Endocrino-Metabólicas	Fortaleza	Bahia	Brazil	60430-350
3	Hospital Ana Nery	Salvador	Bahia	Brazil	40323-010
4	Instituto de Estudos E Pesquisas Clinicas Do Ceara	Fortaleza	Ceará	Brazil
5	Instituto Hospital de Base	Brasília	Distrito Federal	Brazil	70330-150
6	Hospital Universitário Cassiano Antonio de Moraes	Vitória	Espirito Santo	Brazil	29043-260
7	Universidade Federal de Goiás	Goiânia	Goiás	Brazil	74605-020
8	NS Clínica de Diabetes e Endocrinologia Ltda	Goiânia	Goiás	Brazil	90020-090
9	Hospital das Clinicas da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais	Brazil	30130-100
10	Centro de Pesquisa do Hospital Santa Lúcia	Poços De Caldas	Minas Gerais	Brazil	37710-005
11	Medicina Nuclear Alto da XV	Curitiba	Paraná	Brazil
12	Hospital Universitário João de Barros Barreto - UFPA	Belém	Pará	Brazil
13	Pronto Socorro Cardiológico de Pernambuco Prof. Luiz Tavares da Silva	Recife	Pernambuco	Brazil	50100-060
14	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
15	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
16	Centro de Pesquisa Clínica do Coração	Aracaju	Sergipe	Brazil	49055-530
17	Centro de Endocrinologia Geloneze	Campinas	São Paulo	Brazil	13073-350
18	Universidade Estadual de Campinas - UNICAMP	Campinas	São Paulo	Brazil
19	Indacor Servicos Medicos Ltda	Indaiatuba	São Paulo	Brazil
20	Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo	Brazil	14048-900
21	Centro Integrado de Pesquisas	São José Do Rio Preto	São Paulo	Brazil	15090-000
22	Clínica Vilela & Martin	São José Do Rio Preto	São Paulo	Brazil	15090-365
23	Instituto de Cardiologia e Endocrinologia Rio Preto Ltda	São José Do Rio Preto	São Paulo	Brazil	15091-330
24	Clínica Cardiológica	Votuporanga	São Paulo	Brazil	15505-189
25	Santa Casa de Misericordia de Votuporanga	Votuporanga	São Paulo	Brazil
26	Faculdade de Ciências Médicas - Universidade do Estado do Rio de Janeiro	Rio de Janeiro		Brazil	20551-030
27	Clínica de Metabologia e Hipertensão da Universidade Federal de São Paulo	São Paulo		Brazil	04025-010
28	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo		Brazil	05403-000
29	Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo		Brazil	05403-000
30	Instituto Dante Pazzanese de Cardiologia	São Paulo		Brazil
31	Irmandade Da Santa Casa de Misericordia de Sao Paulo	São Paulo		Brazil
32	Real e Benemérita Associação Portuguesa de Beneficência/SP	São Paulo		Brazil

Sponsors and Collaborators

• Hospital Israelita Albert Einstein
• Ministry of Health, Brazil

Investigators

• Study Director: Otavio Berwanger, MD, PhD, Hospital Israelita Albert Einstein

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hospital Israelita Albert Einstein
• ClinicalTrials.gov Identifier: NCT04040634
• Other Study ID Numbers: OPTIMAL-DIABETES Trial; 02795218.8.1001.0071; 25000.028978/2018-02
• First Posted: Aug 1, 2019
• Last Update Posted: May 27, 2022
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cardiovascular Diseases; Hypertension; Diabetes Mellitus

Study Results

No Results Posted as of May 27, 2022