Brazilian Cardioprotective Nutritional Program Trial

Study Overview
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Brief Summary
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There are no studies exploring the benefits of a diet composed of typical Brazilian food in the secondary prevention of cardiovascular diseases. Randomized studies show that the Mediterranean diet is beneficial for patients with established cardiovascular disease or in risk for CVD development. Indeed, nutritional composition of the Mediterranean Diet is one of main references for dietary guidelines for treatment and prevention of CVD in Brazil and the world. However, in many countries, such as Brazil, most foods of the Mediterranean diet are not widely available, may be expensive or are not part of population eating habits. So, the prescription of the Mediterranean diet intervention for cardiovascular disease to the Brazilian population may not be feasible, leading to a low adherence. In this context, patients with established CVD have a low compliance to nutritional prescription. The BALANCE Program, considers 3 concepts: a) A dietary prescription guided by nutritional content recommendations from the Brazilian national guidelines; b) A nutritional education program based on fun, playful strategies and suggestions of affordable foods; and c) Intensive follow-up through one-on-one visits, group sessions, and phone calls. This is the first proposal to use these concepts concurrently with the objective to increase adherence of secondary prevention patients to the diet proposed by the guidelines. Therefore, The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina.

Detailed Description
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The BALANCE Program will investigate the effect of the Program in reducing cardiovascular events, such as cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, hospitalization for unstable angina, or death in patients with established cardiovascular disease. Moreover the aim is to evaluate the effect of the dietary program on reducing cardiovascular risk factors, such as body mass index, waist circumference, blood pressure, total cholesterol, low density lipoprotein (LDL), triglycerides and fasting glucose. Also the objective is to compare the dietary patterns after interventions, the effect of the intervention among nutrients and energy consumption and, finally, to evaluate the BALANCE Program comprehension. The BALANCE Program is a randomized, multicenter, national trial with allocation concealment and intention-to-treat analysis. The elegibility criteria is patients aged 45 years or more with any evidence of established cardiovascular disease to the BALANCE program or control groups. BALANCE Program is composed by 3 concepts: a) a diet that provides 50-60% of energy from carbohydrate, 10-15% from protein, 25-35% from total fat, <7% from saturated fatty acids, <10% polyunsaturated fatty acids, <20% monounsaturated fatty acids, <1% trans fats, <200 mg/day cholesterol, 20-30 g/day fiber, and <2,400 mg/day sodium; b) Nutrition education program based on ludic strategies and indication of affordable foods; c) An intense follow up by individual and group visits and phone calls. For Control group, generalized advices to follow a low fat, low energy, low sodium and low cholesterol diet are given. The primary composite outcome is the occurrence of of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease or hospitalization for unstable angina. Blinded assessors will adjudicate clinical events and analysis will follow the intention-to-treat principle. Were enrolled 2534 patients in 35 sites. Enrollment was open in March 2013 and ended in March 2015 and patients will be followed up to 48 months.

Official Title
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The Brazilian Cardioprotective Nutritional Program to Reduce Events and Risk Factors in Secondary Prevention for Cardiovascular Disease

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Behavioral: BALANCE
* Behavioral: Control diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any evidence of coronary artery disease (CAD) over the preceding 10 years, as defined by any of the following criteria: defined by previous myocardial infarction, stable or unstable angina, history of atherosclerotic stenosis ≥70% of the diameter of any coronary artery on conventional or computed tomographic (CT) coronary angiography, history of angioplasty, stenting, or coronary artery bypass surgery) Any evidence of stroke in the preceding 10 years Peripheral Arterial Disease over the preceding 10 years, as defined by any of the following criteria: ankle/arm ratio <0.9 of systolic blood pressure in either leg at rest, angiography or Doppler demonstrating >70% stenosis in a cardiac artery, intermittent claudication, vascular surgery for atherosclerotic disease, amputation due to atherosclerotic disease, aortic aneurysm Exclusion Criteria: Refusal to provide Informed Consent Statement neurocognitive or psychiatric condition that may hinder collection of reliable clinical data (defined at the trial investigator's discretion) Life expectancy less than 6 months Pregnancy or lactation Liver failure with a history of encephalopathy or anasarca Renal Failure with indication for dialysis Congestive heart failure Previous organ transplantation Wheelchair use Any restrictions to receiving an oral diet.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BALANCE group<br>BALANCE Program is composed by 3 concepts: a) a diet composed of 50-60% of energy from carbohydrate, 10-15% of energy from protein; 25-35% of energy from fat (<7% saturated fatty acid; <10% polyunsaturated fatty acid; <20% monounsaturated fatty acid, <1% trans fatty acid), <200 mg/day of cholesterol, 20-30 g/day of fiber and <2400 mg/day of sodium; b) Nutrition education program based on ludic strategies and indication of affordable foods; c) An intense follow up by individual and group visits and phone calls. | Behavioral: BALANCE<br> <br> * Other names: PABC;;|
| Active Comparator: Control Diet group<br>generalized advices to follow a low fat, low energy, low sodium and low cholesterol diet are given. | Behavioral: Control diet<br>* Participants will be encourage to follow a generalized diet counseling prepared by dietitians based on low fat, low energy, low sodium and low cholesterol diets. They will receive a common folder composed by lists of foods that should be preferred or avoided. For example, avoidance of ultra processed foods, preference for boiled and baked foods rather than fried foods and recommendation of having at least five meals a day. This folder is equivalent of several that are given on ambulatories or hospital of Brazilian public health.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composity of Major Cardiovascular Events | The primary composite outcome will be the occurrence of any of the following cardiovascular events: cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, hospitalization for unstable angina, cardiovascular death, or death from any cause. The Clinical Endpoints Committee (CEC) will be responsible for adjudication of primary composite outcome components. All suspected events will be entered into the CEC tracking database and independently reviewed by two CEC physicians. If the two adjudicators agree, event adjudication will be considered complete. If there is disagreement, the final decision will be made by a third, independent adjudicator. It will be reported in events per person-years and crude rate per 1000 person-years. | up to 48 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total cholesterol (mg/dl) | For biochemical analyses blood samples will be collected and handled according to routine hospital practice. All participants will be fasted for at least 12 hours before phlebotomy. It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations. | up to 48 month | 
| LDL - cholesterol (mg/dl) | For biochemical analyses blood samples will be collected and handled according to routine hospital practice. It will be estinated by Friedewald formula. All participants will be fasted for at least 12 hours before phlebotomy. It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations | up to 48 month | 
| Fasting glucose (mg/dL) | For biochemical analyses blood samples will be collected and handled according to routine hospital practice. All participants will be fasted for at least 12 hours before phlebotomy. It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations. | up to 48 month | 
| Blood pressure (mmHg) | It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations | up to 48 month | 
| Body-mass index (kg/m2) | Compose by body weight (in kilograms) and body height (in meters), reported in kg/m².It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations. | up to 48 month | 
| waist circumference (cm) | It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations. The values of the circumferences will be expressed in centimeters (cm). The waist circumference should be measured through the midpoint between the lower border of the costal arch and the iliac crest in the medial axillary line. | up to 48 month | 
| Triglycerides (mg/dL) | For biochemical analyses blood samples will be collected and handled according to routine hospital practice. All participants will be fasted for at least 12 hours before phlebotomy. It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations | up to 48 month | 
| isolated occurrence of cardiovascular events | cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, hospitalization for unstable angina, or isolated cardiovascular death. The Clinical Endpoints Committee (CEC) will be responsible for adjudication of primary composite outcome components. All suspected events will be entered into the CEC tracking database and independently reviewed by two CEC physicians. If the two adjudicators agree, event adjudication will be considered complete. If there is disagreement, the final decision will be made by a third, independent adjudicator. It will be reported in events per person-years and crude rate per 1000 person-years. | up to 48 month | 
| isolated cardiovascular death or death from any cause | isolated cardiovascular death or death from any cause The Clinical Endpoints Committee (CEC) will be responsible for adjudication of primary composite outcome components. All suspected events will be entered into the CEC tracking database and independently reviewed by two CEC physicians. If the two adjudicators agree, event adjudication will be considered complete. If there is disagreement, the final decision will be made by a third, independent adjudicator. It will be reported in events per person-years and crude rate per 1000 person-years. | up to 48 month | 
| nutrient and energy intake analysis | It will be analyzed over time by repeated-measures analysis of variance using a mixed model or generalized estimating equations. Dietary intake data was assessed from two 24-hour recall from each visit, collected by trained interviewers. Nutrients will be present in grams/day and in % of calories and energy in Kcal. | up to 48 month | 
| dietary pattern analysis | a posteriori and/or a priori analysis. The dietary intake data will be obtain from two 24-hour recalls and the nutrient variability was adjusted by the Multiple Source Method (MSM). Dietary patterns were obtained by principal component analysis, and the scores were categorized into tertiles. | up to 48 month | 
| BALANCE Program comprehension | Each telephone monitoring will address questions about the nutritional guidelines received by the patient in order to identify the understanding of the information after the follow-up visit. The answers will be imputed in an electronic system developed for the telephone monitoring of DICA Br. It will be analysed by chi-square and/or regression analysis. | up to 48 month | 
| Cost-effectiveness analysis of clinical events (U$/events) | A cost-effectiveness analysis will be performed taking into consideration the societal perspective. BALANCE diet cost and the healthcare expenditures will be estimated in both intervention and control groups among individuals who were adherent to BALANCE study protocol. Clinical outcomes will determine the effectiveness of the BALANCE study. The expected clinical outcomes are death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or angina. Differences between the cost-effectiveness rates fwill determine the cost-effectiveness analysis of clinical events. External validity will be performed using sensibility analyses. | up to 36 month | 
| Cost-effectiveness analysis of diet quality (U$/DQIscore) | A cost-effectiveness analysis will be performed taking into consideration the societal perspective. BALANCE diet cost and the healthcare expenditures will be estimated in both intervention and control groups among individuals who were adherent to BALANCE study protocol. Diet quality will be obtained by diet quality index (DQI) and will determine the effectiveness of the BALANCE study. Differences between the cost-effectiveness rates will determine the Cost-effectiveness analysis of diet quality External validity will be performed using sensibility analyses. | up to 36 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular diseases, secondary prevention, diet