Cardiovascular DiseasesPhase 3VitaVasKNCT01742273
Vitamin K1 to Slow Progression of Vascular Calcification in HD Patients
A Phase 3 study testing Vitamin K1 in people with Cardiovascular Diseases, run by RWTH Aachen University at 13 sites in 3 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- Vitamin K1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 13 sitesin 3 countries
- Study dates
- Oct 2013to 17 Jul 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
Germany10 sites
KfH Curatorship for Dialysis and Renal transplantation e.V.
Aachen, 52074
University Hospital of RWTH Aachen, Department of Medicine II
Aachen
Clinical Center of Coburg - Department of Medical Clinic III, Nephrology
Coburg
MVZ DaVita Düsseldorf
Düsseldorf, 40210
KfH Curatorchip for Dialysis and Renal Transplantation e.V.
Düsseldorf
University Hospital Düsseldorf - Department of Nephrology
Düsseldorf
MVZ Diaverum Erkelenz/ Heinsberg
Erkelenz
University hospital of Erlangen - Department of Medicine 4, Nephrology and Hypertension
Erlangen
Internistische Facharztpraxis, Abteilung Kardiologie - Nephrologie, Dialyse Geilenkirchen
Geilenkirchen, 52511
KfH Curatorchip for Dialysis and Renal Transplantation e.V.
Stolberg, 52222
Belgium2 sites
Université catholique de Louvain - Department of Nephrology
Brussels
UZ Leuven, Dept. of Nephrology
Leuven, 3000
Sweden1 site
University Hospital at Huddings, Karolinska Institute Stockholm - Department of Renal Medicine K56
Stockholm
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiovascular Diseases
- Being tested
- Vitamin K1
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin K1Drug
Also called KA-Vit Tropfen (phylloquinone)
Vitamin K1 to slow vascular calcification
| Study group | Role | What they receive |
|---|---|---|
| standard treatment (usual care) | No intervention | standard treatment (usual care) |
| Vitamin K1 | Experimental | Vitamin K1 (phylloquinone), thrice weekly p.o. (5mg) Receives: Drug: Vitamin K1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression of coronary artery calcification and thoracic aortic calcification
Progression of coronary artery calcification and thoracic aortic calcification(absolute change of the volume score at the 18-month MSCT versus the baseline MSCT)
Measured: 18 months
Secondary outcomes (4)
Progression of aortic valve calcification
Progression of aortic valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
Measured: 18 months
Progression of mitral valve calcification
Progression of mitral valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
Measured: 18 months
Mortality from any cause within 18 months after the treatment
Mortality from any cause within 18 months after the treatment
Measured: 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
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
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study startOct 2013
- Primary completion17 Jul 2020
- Study completion17 Jul 2020
Why it stopped: Termination stopped due to low recruitment rates
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jürgen Floege, Prof. Dr., Principal investigator, University Hospital of RWTH Aachen -Department of Medicine II, Nephrology and Clinical Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01742273
- Sponsor's protocol ID
- VitaVasK
- Other IDs
- 2010-021264-14
- Acronym
- VitaVasK
- Status last verified
- Oct 2020
- First submitted
- 3 Dec 2012
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin K1 to Slow Progression of Vascular Calcification in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT01742273
- Acronym / sponsor ID
- VitaVasK / VitaVasK
- Conditions
- Cardiovascular Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Termination stopped due to low recruitment rates
- Enrolment
- 63 participants (actual)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- 17 Jul 2020 (actual)
- Study completion
- 17 Jul 2020 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard treatment (usual care) | No intervention | –standard treatment (usual care) |
| Vitamin K1 | Experimental | Drug: Vitamin K1Vitamin K1 (phylloquinone), thrice weekly p.o. (5mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (20 listed)
- Known hypersensitivity against Vitamin K1
- History of thrombosis
- intake of Vitamin K
- tumor disease
- pulse >100/min (resting heart rate)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin K1Also: KA-Vit Tropfen (phylloquinone)Vitamin K1 to slow vascular calcification | Drug | Vitamin K1 |
Primary outcome
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)
4 secondary outcomes
Progression of aortic valve calcification
Time frame: 18 months
Progression of mitral valve calcification
Time frame: 18 months
Mortality from any cause within 18 months after the 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
Time frame: 6 years
Results and safety
The study was stopped early (reason given: Termination stopped due to low recruitment rates). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jürgen Floege, Prof. Dr. principal investigator
University Hospital of RWTH Aachen -Department of Medicine II, Nephrology and Clinical Immunology
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin K1 in people with Cardiovascular Diseases, run by RWTH Aachen University at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, Belgium, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Termination stopped due to low recruitment rates). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression of coronary artery calcification and thoracic aortic calcification (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.