Project title:
Vitamin K1 to slow vascular calcification in hemodialysis patients (VitaVasK)
Logo of the Project (if available):
Estimated length / Total length (if the project was already concluded): 3 years
Starting date: 05/07/2013
Ending date: 05/07/2016
Name of the Principal Investigator:
Prof. Dr. Juergen Floege, University Hospital Aachen, Germany
List of the collaborators:
Germany:
1.
2.
3.
4.
5.
6.
PD Dr. Thilo Krüger, PD Dr. Georg Schlieper, University Hospital Aachen, Germany
Dr. med. Roland Böhm, Dr. med. Maria Ritzerfeld- Bockstegers, KfH Aachen
PD Dr. Johannes Jacobi; Dr. Michael Leidig, Erlangen, Germany
Prof. Dr. Lars-Christian Rump; PD Dr. Ralf Westenfeld; Dr. J. Stegbauer, Duesseldorf, Germany
Prof. Dr. Markus Ketteler; Dr. Hansjörg Rothe, Coburg, Germany
Prof. Dr. Andreas Kribben, Essen, Germany
7.
8.
9.
10.
11.
Prof. Dr. Michel Jadoul, Mercedes Vignioble, Brussels, Belgium
Prof. Pieter Evenepoel, Leuven, Belgium
Prof. Dr. Peter Stenvinkel, Stockholm, Sweden
Prof. Dr. Andrzej Wiecek; Grzegorz Piecha MD PhD, Katowice, Poland
Dr. Leon Schurgers, CARIM, University of Maastricht, Netherlands
EU:
List of the centres / institutions involved:
Internal Medicine II, Dept. of Nephrology & Clinical Nephrology;
RWTH Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany
& associates:
KfH Kuratorium für Dialyse und Nierentransplantation e.V. KfH-Nierenzentrum Schurzelter Str. 564, 52074
Aachen, Germany
MVZ Diaverum Erkelenz, Tenholter Straße 43A, 41812 Erkelenz, Germany
Dept. of Radiology; RWTH Aachen University, Pauwelsstr. 30; Aachen, Germany
University Hospital Erlangen. Dept. of Medicine 4, Nephrology and Hypertension,
Krankenhausstrasse 12
91054 Erlangen, Germany
& associates:
Hospital Nuremberg, Breslauer Straße 201
90471 Nürnberg
University Hospital Duesseldorf. Dept. of Nephrology,
Moorenstr. 5,
40225 Düsseldorf, Germany
Clinical Center of Coburg III, Medical Clinic, Nephrology
Ketschendorfer Straße 33,
96450 Coburg , Germany
& associates:
KfH Kuratorium für Dialyse und Nierentransplantation e.V. KfH-Nierenzentru mGustav-Hirschfeld-Ring 8,
96450 Coburg
University Hospital Essen, Klinik für Nephrologie
Hufelandstraße 55,
45147 Essen, Germany
Université catholique de Louvain, Dept. of Nephrology.
10 Avenue Hippocrate;
1200 Brussels, Belgium
Karolinska Institute Stockholm, Dept. of Renal Medicine K5
University Hospital at Huddinge
14186 Stockholm, Sweden
University Hospital of Silesia in Katowice, Dept. Nephrology,
Endocrinology Metabolic Diseases
Poniatowskiego 15, 40-027 Katowice, Poland
CARIM, Universität Maastricht, Universiteitssingel 50
6200 MD Maastricht, Netherlands
SPONSOR
RWTH Aachen University represented by the Clinical Trials Center
Aachen (CTC-A) of the Medical Faculty of the RWTH Aachen University
Coordinating Director: Dipl. Biol. Verena Deserno MA; Pauwelsstr. 30, 52074 Aachen, Germany
MEDICAL STATISTICS
Medical Statistics; RWTH Aachen University, Pauwelsstr. 30; Prof. Dr. Ralf-Dieter Hilgers;Pauwelsstr. 30,
52074 Aachen (Germany)
Proposed research -max 500 words-:
VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-02126414) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice
computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary
calcification volume score of at least 100 will be randomized to continue on standard care or to
receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration
will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are
the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes
in the volume cores at the 18-month MSCT versus the baseline MSCT). Secondary end points
comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse
cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and allcause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may
lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.
Aim of the research -max 500 words-:
The overall aim of the VitaVasK study is to explore and subsequently confirm whether a vitamin K1based therapy attenuates the progression/can prevent or revert vascular calcification of thoracic
aortic and coronary artery calcification compared to standard treatment. Globally, approximately
500 million patients suffer from chronic kidney disease and 2.2 million require dialysis treatment.
Compared to the general population, patients with advanced chronic kidney disease experience a
10 – 100x increased risk of cardiovascular complications, which translates into a mortality risk
comparable to the one found in patients with metastatic cancer disease. This problematic situation
is further complicated by the fact that many treatment strategies (including statins, increased
dialysis dose and erythropoietin), in randomized controlled trials have not been shown to improve
survival in this
patient group. A major problem in dialysis patients is accelerated vascular calcification; a process
that increases the risk of cardiovascular complications and premature death. Strategies that
interfere with the progress of vascular calcification are urgently needed. Vitamin K1
supplementation may be a novel effective and well tolerated treatment strategy to slow down the
calcification process and lower the risk of cardiovascular complications.
Given a successful outcome of the clinical trial, Vitamin K1 will be the first substance proving an
attenuation of vascular calcification in a larger cohort of dialysis patients. The trial is powered to
detect a difference in vascular calcification between the treatment and control group; nevertheless,
mortality is as well listed as a secondary end point. As vascular calcification is an independent risk
factor for cardiovascular mortality and morbidity, this trial may give direct or indirect reason for a
treatment option for a major risk factor of dialysis patients.
Progress and results as of July 2015 (if still ongoing) or at the Study conclusion (if concluded) -max 500
words-:
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26 patients have been screened and 9 have been randomized. 17 Screen failures occurred. 1
patient finalized the study and 1 patient withdrew consent after starting treatment. To date, 7
patients are active in the study.
The Milan center was removed from the list of participating centers due to prolonged submission
process and lack of perspective to apply for VitaVasK in a meaningful time.
The center of Leuven, has been contacted submission is in preparation. Here, CT calibration has not
been performed yet which will be done after successful EC application.
The application process is finalized in Stockholm, Sweden, and on course in all remaining European
centers and initiation of the sites is expected within the next weeks to months.
No results are available as the study is still ongoing.
List of the papers published in peer review journals:
Krueger T, Schlieper G, Schurgers L, Cornelis T, Cozzolino M, Jacobi J, Jadoul M, Ketteler M, Rump
LC, Stenvinkel P, Westenfeld R, Wiecek A, Reinartz S, Hilgers RD, Floege J.
Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and
study protocol.
Nephrol Dial Transplant. 2014 Sep;29(9):1633-8.
List of the presentations done at major congresses/meetings:
None.
As of August 2015