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

• ClinicalTrials.gov Identifier: NCT03073018
• Recruitment Status: Completed
• First Posted: March 8, 2017
• Last Update Posted: March 10, 2017
• Sponsor: University Medical Center Groningen
• Collaborators: Dutch Kidney Foundation; Netherlands Heart Foundation
• Information provided by (Responsible Party): Prof. Wiek H. van Gilst, University Medical Center Groningen

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Microalbuminuria; Cardiovascular Diseases; Renal Disease	Drug: Fosinopril; Drug: Pravastatin; Drug: Fosinopril Placebo; Drug: Pravastatin Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 864 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Prevention of Renal and Vascular Endstage Disease Intervention Trial
• Study Start Date: April 1998
• Actual Primary Completion Date: June 2003
• Actual Study Completion Date: November 2003

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Combined incidence of all-cause mortality, MACE and/or end-stage renal disease [ Time Frame: 4 years ]
   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

Secondary Outcome Measures :

1. Incidence of all-cause mortality [ Time Frame: 4 years ]
   Incidence of all-cause mortality
2. effect of treatment on microalbuminuria [ Time Frame: 4 years ]
   albumin excretion mg/24 h
3. effect of treatment on LDL cholesterol [ Time Frame: 4 years ]
   in mmol/L
4. effect of treatment on blood pressure [ Time Frame: 4 years ]
   in mmHg
5. Incidence of hospital admission [ Time Frame: 4 years ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

University Medical Center Groningen

Dutch Kidney Foundation

Netherlands Heart Foundation

Investigators

• Principal Investigator: Wiek H van Gilst, PhD; UMCG

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Prof. Wiek H. van Gilst, Principal Investigator, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT03073018
• Other Study ID Numbers: METc 97/10/172
• First Posted: March 8, 2017
• Last Update Posted: March 10, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Cardiovascular Diseases; Fosinopril; Pravastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Antihypertensive Agents