Primary Prevention of Cardiovascular Disease (CVD) in Pre-diabetic & Pre-hypertensive Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treating pre-diabetic & pre-hypertensive individuals using multiple drugs intervention (anti-hypertensive drugs (i.e., ACEI) plus anti-glycemic drug (i.e., metformin) plus anti-hyperlipidemic drug (statin)) would lower Cardiovascular Disease (CVD) events.

Detailed Description
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The risks of CVD are not confined to a subset of established hypertensive or diabetic population, but also increase among those with suboptimal blood pressure and glycemic level, namely pre-hypertensive or pre-diabetic population. Evidence on the effectiveness of drug interventions to lower CVD events in pre-clinical stage population has been scant.

Official Title
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Primary Prevention of Cardiovascular Disease in Pre-diabetic & Pre-hypertensive Subjects Using Multiple Risks Reduction Strategy: A Multi-center, Double-blind, Randomized Controlled Trial

Conditions
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Pre-diabetes, Pre-hypertension

Intervention / Treatment
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* Drug: Metformin+Enalapril+Simvastatin
* Drug: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-diabetes Pre-hypertensives LDL-Cholesterol >= 100 < 190 mg/dl BMI >= 23 Estimated GFR >= 60 ml/min/1.73 m2 (MDRD equation) Willing to participate and provide written inform consent Exclusion Criteria: Current involved in other studied medications Regular use of corticosteroids Current use of weight loss medication History of renal disease Active liver disease including jaundice, chronic hepatitis with ALT >= 2.5 the upper normal limit Active malignancy Major psychiatric disorder Diseases and medications that affect glucose tolerance (e.g. pheochromocytoma, Cushing's syndrome, acromegaly, steroid-dependent asthma, protease inhibitors, antipsychotics) Nursing women, pregnant women, or those that plan to become pregnant in the study period

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin+Enalapril+Simvastatin<br> | Drug: Metformin+Enalapril+Simvastatin<br>* Poly-pill - composed of Metformin (500 mg), Enalapril (10 mg) and Simvastatin (10 mg) in single tablet given once daily after dinner for 4 years<br>* Other names: Poly-pill;|
| Placebo Comparator: Placebo tablet<br> | Drug: Placebo tablet<br>* Identical Placebo Tablet<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Events | Fatal or Non-fatal Myocardial Infarction, Angina Pectoris, Congestive Heart Failure, Coronary Revascularization, Fatal or Non-fatal Stroke, Amputation of Lower Extremities (non-traumatic cause) | 4-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Micro-vascular Complications | Renal dysfunction, ESRD (on dialysis or kidney transplantation), Progression of Albuminuria, Retinopathy | 4-year | 
| Cumulative Incidence of Diabetes |  | 4-year | 
| Cumulative Incidence of Hypertension |  | 4-year | 
| Incidence of Individual Cardiovascular Disease | Coronary Artery Disease - Myocardial Infarction, Angina Pectoris, Congestive Heart Failure, Coronary Revascularization Stroke- Cerebral Hemorrhage, Cerebral Infarction, Subarachnoid Hemorrhage Peripheral Artery Disease- Leg amputation, endovascular or surgical intervention in leg arteries | 4-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Impaired fasting glucose, Impaired glucose tolerance, Pre-diabetes, Pre-hypertensives, Cardiovascular events