Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND-IT)

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Microalbuminuria; Renal Disease
• Intervention / Treatment: Drug: Fosinopril; Drug: Pravastatin; Drug: Pravastatin Placebo; Drug: Fosinopril Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 864
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Netherlands Heart Foundation; Dutch Kidney Foundation
• Investigators: Principal Investigator: Wiek H van Gilst, PhD, UMCG

Publications and helpful links

General Publications

• Diercks GF, Janssen WM, van Boven AJ, Bak AA, de Jong PE, Crijns HJ, van Gilst WH. Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT]). Am J Cardiol. 2000 Sep 15;86(6):635-8. doi: 10.1016/s0002-9149(00)01042-0.
• Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, de Zeeuw D, de Jong PE, van Veldhuisen DJ, van Gilst WH; Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004 Nov 2;110(18):2809-16. doi: 10.1161/01.CIR.0000146378.65439.7A. Epub 2004 Oct 18.
• Kofink D, Eppinga RN, van Gilst WH, Bakker SJL, Dullaart RPF, van der Harst P, Asselbergs FW. Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial). Circ Cardiovasc Genet. 2017 Dec;10(6):e001759. doi: 10.1161/CIRCGENETICS.117.001759.

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): June 1, 2003
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (Actual): March 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; 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; Pravastatin; Fosinopril
• Other Study ID Numbers: METc 97/10/172

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED