Vitamin K1 to Slow Progression of Vascular Calcification in HD Patients (VitaVasK)

October 6, 2020 updated by: RWTH Aachen University

Vitamin K1 to Slow Progression of Vascular Calcification in Hemodialysis Patients

Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular mortality associated with extensive vascular calcification (VC). In the past years the development of VC was discovered to be actively regulated and as being influenced by inhibitors of calcification (e.g. matrix-Gla-protein, fetuin-A). MGP is produced by vascular smooth muscle cells and needs post-translational modification by vitamin K dependent gamma-carboxylation to be fully active. Based on the demonstration of increased PIVKA-II levels, about 97% of all HD patients exhibit insufficient carboxylation activity. We therefore aim in this randomized, controlled study to retard the progress of coronary and aortal calcification as assessed by thoracic multislice-CT by the thrice weekly administration of 5 mg vitamin K1 (phylloquinone) to about 100 HD patients over a period of 18 months.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular mortality associated with extensive vascular calcification (VC). This forms - at least partially - the reason for the excessively increased cardiovascular mortality in this population.

In the past years the development of VC was discovered to be actively regulated and as being influenced by inhibitors of calcification (e.g. matrix-Gla-protein, fetuin-A). Matrix Gla protein (MGP) is a powerful vascular wall-based inhibitor of VC. MGP is produced by vascular smooth muscle cells and needs post-translational modification by vitamin K dependent gamma-carboxylation to be fully active. The role of MGP was discovered in knock-out mice, which died from rupture of a massively calcified aorta. Functional vitamin K deficiency induced by administration of warfarin leads to the development of VC, which in turn can be inhibited by subsequent administration of vitamin K1. Warfarin inhibits the vitamin K mediated gamma-carboxylation, which leads to the production of noncarboxylated and inactive MGP (ucMGP).

Warfarin is widely used due to its inhibitory capacity on the activation of coagulation factors. Now it has been discovered that the use of vitamin K inhibitors influences vascular health: long-term use of warfarin is associated with an increased prevalence and extent of VC in the normal population and HD patients. Warfarin is also a crucial risk factor for the development of calciphylaxis, a life-threatening complication in HD patients characterised by calcified cutaneous vessels. In turn, administration of vitamin K1 was accompanied by reduced intima-media-thickness (IMT) and increased elasticity of vessels in postmenopausal women.

Based on the demonstration of increased PIVKA-II levels, about 97% of all HD patients exhibit insufficient carboxylation activity. Together with the increased VC they represent an ideal population for interventional trials in the vitamin K system. Recently we were able to demonstrate that supplementation of vitamin K1 in such patients is well tolerated, shows only very few side effects and induces a dose dependent decrease of the inactive form Dephosphorylated noncarboxylated matrix Gla protein (dpucMGP) in serum over a six weeks period. In this trial we also observed that all dialysis patients included had insufficient vitamin K serum levels, indicating no substantial influence of food intake on vitamin K deficiency. In addition, this demonstrates that all patients have insufficient vitamin K levels to facilitate adequate MGP carboxylation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Université catholique de Louvain - Department of Nephrology
      • Leuven, Belgium, 3000
        • UZ Leuven, Dept. of Nephrology
  • Germany
      • Aachen, Germany
        • University Hospital of RWTH Aachen, Department of Medicine II
      • Aachen, Germany, 52074
        • KfH Curatorship for Dialysis and Renal transplantation e.V.
      • Coburg, Germany
        • Clinical Center of Coburg - Department of Medical Clinic III, Nephrology
      • Düsseldorf, Germany, 40210
        • MVZ DaVita Düsseldorf
      • Düsseldorf, Germany
        • KfH Curatorchip for Dialysis and Renal Transplantation e.V.
      • Düsseldorf, Germany
        • University Hospital Düsseldorf - Department of Nephrology
      • Erkelenz, Germany
        • MVZ Diaverum Erkelenz/ Heinsberg
      • Erlangen, Germany
        • University hospital of Erlangen - Department of Medicine 4, Nephrology and Hypertension
      • Geilenkirchen, Germany, 52511
        • Internistische Facharztpraxis, Abteilung Kardiologie - Nephrologie, Dialyse Geilenkirchen
      • Stolberg, Germany, 52222
        • KfH Curatorchip for Dialysis and Renal Transplantation e.V.
  • Sweden
      • Stockholm, Sweden
        • University Hospital at Huddings, Karolinska Institute Stockholm - Department of Renal Medicine K56

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or Female minimum 18 years of age
  • Not less than 6 months on hemodialysis
  • Cardiovascular calcification percent (coronary artery volume score > 100)
  • Written consent to take part in the study
  • Life expectancy not less than 18 months

Exclusion Criteria:

  • Known hypersensitivity against Vitamin K1
  • History of thrombosis
  • intake of Vitamin K
  • tumor disease
  • pulse >100/min (resting heart rate)
  • Intake of vitamin K antagonists (e.g. Marcumar) at baseline or in the 3 months prior to baseline
  • Inflammatory bowel disease
  • Short-bowel syndrome
  • Significant liver dysfunction
  • more than one stent in one coronary artery plus one or more stents in an additional artery
  • Hemoglobin < 70 g/L
  • Women who are pregnant or breastfeeding
  • Women without sufficient contraception
  • Alcohol or drug abuse
  • Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
  • Subject unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up-visits and unlikelihood of completing the study
  • Participation in a parallel clinical trial or participation in another clinical trial within the previous 3 months
  • Subjects who are in any state of dependency to the sponsor or the investigators
  • Employees of the sponsor or the investigators
  • Subjects who have been committed to an institution by legal or regulatory order

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
NO_INTERVENTION: standard treatment (usual care)
EXPERIMENTAL: Vitamin K1
Vitamin K1 (phylloquinone), thrice weekly p.o. (5mg)
Drug: Vitamin K1
Vitamin K1 to slow vascular calcification
Other Names:
  • KA-Vit Tropfen (phylloquinone)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression of coronary artery calcification and thoracic aortic calcification
Time Frame: 18 months
Progression of coronary artery calcification and thoracic aortic calcification(absolute change of the volume score at the 18-month MSCT versus the baseline MSCT)
18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression of aortic valve calcification
Time Frame: 18 months
Progression of aortic valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
18 months
Progression of mitral valve calcification
Time Frame: 18 months
Progression of mitral valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
18 months
Mortality from any cause within 18 months after the treatment
Time Frame: 6 years
Mortality from any cause within 18 months after the treatment
6 years
Major adverse cardiovascular events: myocardial infarction, stroke, acute coronary syndrome,embolism, symptom-driven revascularization, death from cardiovascular cause within 18 months after start of treatment
Time Frame: 6 years
Major adverse cardiovascular events: myocardial infarction, stroke, acute coronary syndrome,embolism, symptom-driven revascularization, death from cardiovascular cause within 18 months after start of treatment
6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RWTH Aachen University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jürgen Floege, Prof. Dr., University Hospital of RWTH Aachen -Department of Medicine II, Nephrology and Clinical Immunology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 17, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 17, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 3, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 5, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 8, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VitaVasK
  • 2010-021264-14 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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