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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pre-diabetes; Pre-hypertension
• Intervention / Treatment: Drug: Metformin+Enalapril+Simvastatin; Drug: Placebo tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 8900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Phisitt Vejakama, M.D.; Phone Number: 66849562882; Email: toughcountrydoc@gmail.com
• Study Contact Backup: Name: Ammarin Thakkinstian, Ph.D.; Phone Number: 66818436266; Email: raatk@mahidol.ac.th

Study Locations

• Thailand
  • Ubon ratchathani
    • Muang District, Ubon ratchathani, Thailand, 34000
      • Ubon ratchathani Public Health Office
      • Principal Investigator: Phisitt Vejakama, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo tablet	Drug: Placebo tablet; Identical Placebo Tablet; Other Names: Placebo
Experimental: Metformin+Enalapril+Simvastatin	Drug: Metformin+Enalapril+Simvastatin; 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; Other Names: Poly-pill

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ramathibodi Hospital
• Collaborators: National Health Security Office, Thailand; Ubon Ratchathani Public Health Office, Thailand; The Government Pharmaceutical Organization
• Investigators: Principal Investigator: Phisitt Vejakama, M.D., Section for clinical epidemiology and bioststistics, Faculty of medicine, Ramathibodi hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Estimate): June 2, 2011
• Last Update Submitted That Met QC Criteria: June 1, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Pre-diabetes; Impaired fasting glucose; Impaired glucose tolerance; Cardiovascular events; Pre-hypertensives
• Additional Relevant MeSH Terms: Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Cardiovascular Diseases; Prehypertension; Prediabetic State; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Metformin; Enalapril; Simvastatin
• Other Study ID Numbers: 12011