Clinical trial NCT03073018: Prevention of Renal and Vascular Endstage Disease Intervention Trial
Official title: Prevention of Renal and Vascular Endstage Disease Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Microalbuminuria
Cardiovascular Diseases
Renal Disease
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Dutch Kidney Foundation
name: Netherlands Heart Foundation
First posted: 2017-03-08
Enrollment: 864
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Combined incidence of all-cause mortality, MACE and/or end-stage renal disease
timeFrame: 4 years
Secondary outcomes:
measure: Incidence of all-cause mortality
timeFrame: 4 years
measure: effect of treatment on microalbuminuria
timeFrame: 4 years
measure: effect of treatment on LDL cholesterol
timeFrame: 4 years
measure: effect of treatment on blood pressure
timeFrame: 4 years
measure: Incidence of hospital admission
timeFrame: 4 years
Other outcomes:
Locations:
Study officials:
affiliation: UMCG
name: Wiek H van Gilst, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.