Clinical trial NCT00169910: VIP: Vascular Imaging Project. Study on the Progression of Cardiovascular Disease in Renal Transplant Recipients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Disease
Keywords: Renal Transplantation
Calcineurin Inhibitor
Mycophenolate Mofetil
Cardiovascular Disease
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Primary endpoint: progression of subclinical cardiovascular disease as assessed by intima media thickness (IMT), pulse wave velocity (PWV) and left ventricular hypertrophy (LVH)
timeFrame: 3 years
Secondary outcomes:
measure: Secondary endpoint: Cardiovascular risk factors: a) Hypertension, b) Hyperlipidemia, c) Diabetes mellitus/glucose intolerance
timeFrame: 3 years
measure: Graft function
timeFrame: 1 year, 3 years
measure: Incidence of acute rejection
timeFrame: 1 year, 3 years
measure: Graft survival (creatinine clearance < 15 ml/min or dialysis)
timeFrame: 1 year, 3 years
measure: Patient survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Johan W. de Fijter, MD,PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.