Prevention of Renal and Vascular Endstage Disease Intervention Trial

Study Overview
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Brief Summary
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The Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) was designed to determine whether intervention with the angiotensin-converting enzyme (ACE) inhibitor fosinopril and/or the hydroxymethylglutaryl coenzyme A reductase inhibitor pravastatin reduced cardiovascular and renal events in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria.

Detailed Description
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This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.

Official Title
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Prevention of Renal and Vascular Endstage Disease Intervention Trial

Conditions
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Microalbuminuria, Cardiovascular Diseases, Renal Disease

Intervention / Treatment
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* Drug: Fosinopril
* Drug: Pravastatin
* Drug: Fosinopril Placebo
* Drug: Pravastatin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent microalbuminuria (urinary albumin excretion >10mg/L once in an early morning spot urine and 15 to 300 mg/24 hours at least once in two 24-hour urine samples) No hypertension (RR <160/100 mm Hg, no anti-hypertensive medication) No hypercholesterolemia (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid-lowering medication) Exclusion Criteria: Creatinine clearance >60% of the normal age-adjusted value Serum potassium >5.5 mmol/L History of chronic liver disease Lactate dehydrogenase, aspartate-amino transferase or alanine-amino transferase >3 times the upper limit of normal Use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists Use of insulin Previously documented allergy or intolerance to study drugs Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosinopril + Pravastatin<br>Fosinopril (20 mg) + pravastatin (40 mg) once daily for 4 years | Drug: Fosinopril<br>* oral administration, capsules<br>* Other names: Monopril;Drug: Pravastatin<br>* oral administration, capsules<br>* Other names: Pravachol;|
| Active Comparator: Fosinopril + Placebo<br>Fosinopril (20 mg) + pravastatin placebo once daily for 4 years | Drug: Fosinopril<br>* oral administration, capsules<br>* Other names: Monopril;Drug: Pravastatin Placebo<br>* oral administration, capsules<br>|
| Active Comparator: Pravastatin + Placebo<br>Pravastatin (40 mg) + fosinopril placebo once daily for 4 years | Drug: Pravastatin<br>* oral administration, capsules<br>* Other names: Pravachol;Drug: Fosinopril Placebo<br>* oral administration, capsules<br>|
| Placebo Comparator: Double Placebo<br>Fosinopril placebo and pravastatin placebo once daily for 4 years | Drug: Fosinopril Placebo<br>* oral administration, capsules<br>Drug: Pravastatin Placebo<br>* oral administration, capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined incidence of all-cause mortality, MACE and/or end-stage renal disease | Combined incidence of all-cause mortality or hospital admission for documented (1) non-fatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all-cause mortality | Incidence of all-cause mortality | 4 years | 
| effect of treatment on microalbuminuria | albumin excretion mg/24 h | 4 years | 
| effect of treatment on LDL cholesterol | in mmol/L | 4 years | 
| effect of treatment on blood pressure | in mmHg | 4 years | 
| Incidence of hospital admission | Incidence of hospital admission for documented (1) non-fatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease | 4 years |