VIP: Vascular Imaging Project. Study on the Progression of Cardiovascular Disease in Renal Transplant Recipients

VIP: Vascular Imaging Project. Prospective Randomized Study on the Effect of AUC-monitored Treatment With Steroids Combined With Either a Calcineurin Inhibitor or Mycophenolate Mofetil on the Progression of Subclinical Cardiovascular Disease in Renal Transplant Recipients.

This is a prospective randomized study to compare the influence of area under the curve (AUC)-monitored dual treatment with steroids in combination with either a calcineurin inhibitor (CNI) or mycophenolate mofetil (MMF) on the progression of subclinical cardiovascular disease in renal transplant recipients.

Since CNI have a detrimental effect on cardiovascular risk factors, it is the researchers' hypothesis that renal recipients after CNI withdrawal will have more reduction of markers of cardiovascular disease.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: AUC monitored withdrawal of MMF or CNI

Detailed Description

Stable renal transplant patients on maintenance immunosuppressive therapy with steroids, a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) will be randomized for AUC-monitored withdrawal of either CNI or MMF.

The progression of cardiovascular markers will be assessed by yearly measurements of Intima Media Thickness, Pulse Wave Velocity and Left Ventricular Hypertrophy in both groups.

The duration of the study will be 3 years and the target sample size is 100 patients per arm

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2300 RC
    • Leiden University Medical Center

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:

• Patients, 18 years or older, on triple maintenance therapy with cyclosporine or tacrolimus , MMF and steroids
• Informed consent

Exclusion Criteria:

• Calculated creatinine clearance < 30 ml/min
• Multi-organ recipients
• Patients with a (historic) panel reactive antibody (PRA) >60%
• Third renal transplant or more.
• Patients receiving investigational drugs other than MMF in combination with cyclosporine or tacrolimus
• Solid malignancy, post-transplant lymphoproliferative disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; AUC monitored withdrawal of MMF	Drug: AUC monitored withdrawal of MMF or CNI; AUC monitored withdrawal of MMF or CNI from a immunosuppressive drug regimen with steroids, CNI and MMF in stable renal transplant recipients
Active Comparator: 2; AUC monitored withdrawal of CNI	Drug: AUC monitored withdrawal of MMF or CNI; AUC monitored withdrawal of MMF or CNI from a immunosuppressive drug regimen with steroids, CNI and MMF in stable renal transplant recipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary endpoint: progression of subclinical cardiovascular disease as assessed by intima media thickness (IMT), pulse wave velocity (PWV) and left ventricular hypertrophy (LVH)	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient survival	3 years
Secondary endpoint: Cardiovascular risk factors: a) Hypertension, b) Hyperlipidemia, c) Diabetes mellitus/glucose intolerance	3 years
Graft function	1 year, 3 years
Incidence of acute rejection	1 year, 3 years
Graft survival (creatinine clearance < 15 ml/min or dialysis)	1 year, 3 years

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Study Chair: Johan W. de Fijter, MD,PhD, Leiden University Medical Center

Publications and helpful links

General Publications

• Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999 May 11;99(18):2434-9. doi: 10.1161/01.cir.99.18.2434.
• O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999 Jan 7;340(1):14-22. doi: 10.1056/NEJM199901073400103.
• Schnuelle P, van der Heide JH, Tegzess A, Verburgh CA, Paul LC, van der Woude FJ, de Fijter JW. Open randomized trial comparing early withdrawal of either cyclosporine or mycophenolate mofetil in stable renal transplant recipients initially treated with a triple drug regimen. J Am Soc Nephrol. 2002 Feb;13(2):536-543. doi: 10.1681/ASN.V132536.
• Mourer JS, de Koning EJ, van Zwet EW, Mallat MJ, Rabelink TJ, de Fijter JW. Impact of late calcineurin inhibitor withdrawal on ambulatory blood pressure and carotid intima media thickness in renal transplant recipients. Transplantation. 2013 Jul 15;96(1):49-57. doi: 10.1097/TP.0b013e3182958552.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 13, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Renal Transplantation; Cardiovascular Disease; Mycophenolate Mofetil; Calcineurin Inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: P05.105