Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K (TReVasc-HDK)

National University Health System, Singapore

Status and phase: Completed; Phase 2

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

Treatments: Drug: menaquinone-7

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02870829

NHG DSRB Ref: 2015/01000

Details and patient eligibility

About

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.

Enrollment: 178 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 45 years and less than 80 years
2. At least 12 months on Hemodialysis
3. Coronary artery calcium score of ≥ 30 in the baseline Multislice Computed Tomography
4. Able to give informed consent
5. Life expectancy of at least18 months

Exclusion criteria

1. History of thrombosis in the last 6 months except vascular access thrombosis
2. Need for vitamin K antagonists therapy at baseline or in the 3 months prior to baseline
3. Presence of significant gut disease (inflammatory bowel disease, short-bowel syndrome)
4. Liver dysfunction
5. Alcohol or drug abuse
6. Presence of coronary stent or have undergone coronary artery bypass grafting
7. Women who are pregnant or breast feeding,
8. Those who are fearful of confined space and cannot lie still for Multislice Computed Tomography
9. Lack of safe contraceptive measures.
10. Those who had parathyroid surgery done.
11. Those with parathyroid hormone (PTH) > 150 pmol/l
12. Patient taking multivitamins containing vitamin K
13. Patient allergic to soy based products

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

178 participants in 2 patient groups

Vitamin K2

Experimental group

Description:

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

Treatment:

Drug: menaquinone-7

Standard Therapy

No Intervention group

Description:

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