Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K

Study Overview
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Brief Summary
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The proposed study will seek to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients in Asian population. It will also evaluate the efficacy of vitamin K 2 supplementation in reducing the progression of vascular calcification in this group of patients. This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis.Primary outcome will be absolute difference in coronary artery calcium (CAC) score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular events (MACE) over the same period.

Official Title
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Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K (Trevasc-HDK): A Study Protocol for a Randomized Controlled Trial

Conditions
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Vascular Calcification, Systemic and Arterial Stiffness, Complication of Hemodialysis, Deficiency of Vitamin K2

Intervention / Treatment
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* Drug: menaquinone-7


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 45 years and less than 80 years At least 12 months on Hemodialysis Coronary artery calcium score of ≥ 30 in the baseline Multislice Computed Tomography Able to give informed consent Life expectancy of at least18 months Exclusion Criteria: History of thrombosis in the last 6 months except vascular access thrombosis Need for vitamin K antagonists therapy at baseline or in the 3 months prior to baseline Presence of significant gut disease (inflammatory bowel disease, short-bowel syndrome) Liver dysfunction Alcohol or drug abuse Presence of coronary stent or have undergone coronary artery bypass grafting Women who are pregnant or breast feeding, Those who are fearful of confined space and cannot lie still for Multislice Computed Tomography Lack of safe contraceptive measures. Those who had parathyroid surgery done. Those with parathyroid hormone (PTH) > 150 pmol/l Patient taking multivitamins containing vitamin K Patient allergic to soy based products

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin K2<br>Vitamin K comes in various isoforms and we have elected to use the K2 isoform - menaquinone-7. We have chosen a dose of 360mcg 3x/week as previous studies using menaquinone-7 demonstrated an increasing dose efficacy relationship up to this strength. Vitamin K2 is manufactured by Nattopharma | Drug: menaquinone-7<br>* Oral supplement given post dialysis 3x/week<br>|
| No Intervention: Standard Therapy<br>Subjects randomised to standard therapy will continue to receive dialysis and chronic kidney disease-metabolic bone disease (CKD-MBD) management in accordance to current best practise guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute difference in coronary artery calcium score at 18-month between control and intervention arms | Comparison made using the t-test following log transformation. Adjustment for baseline CAC scores made via the analysis of covariance. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute difference in AVC score at 18-months | Comparison made using the t-test following log transformation. Adjustment for baseline AVC scores made via the analysis of covariance. | 18 months | 
| Percentage of patients with regression of CAC of ≥ 10% over 18-month |  | 18 months | 
| Absolute difference in cfPWV and AI at 18-months |  | 18 months | 
| Mortality from any cause within the study period |  | 18 months | 
| MACE defined as non-fatal myocardial infarction, heart failure, acute coronary syndrome, need for coronary revascularization, non-fatal stroke, significant peripheral vascular disease |  | 18 months | 
| Difference in plasma levels of dp-ucMGP at 18 months |  | 18 months | 
| Vascular access events, including clotting requiring insertion of a new dialysis catheter, declotting or exchange of an existing catheter, and vascular intervention during the study period |  | 18 months |