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

• ClinicalTrials.gov Identifier: NCT02870829
• Recruitment Status: Completed
• First Posted: August 17, 2016
• Last Update Posted: May 5, 2022
• Sponsor: National University Health System, Singapore
• Collaborators: National Medical Research Council (NMRC), Singapore; Nattopharma ASA
• Information provided by (Responsible Party): Sabrina Haroon Wong Peixin, National University Health System, Singapore

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Vascular Calcification; Systemic and Arterial Stiffness; Complication of Hemodialysis; Deficiency of Vitamin K2	Drug: menaquinone-7	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K (Trevasc-HDK): A Study Protocol for a Randomized Controlled Trial
• Actual Study Start Date: July 2016
• Actual Primary Completion Date: February 2022
• Actual Study Completion Date: February 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vitamin K2; 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; Oral supplement given post dialysis 3x/week
No Intervention: Standard Therapy; 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

Outcome Measures

Primary Outcome Measures :

1. Absolute difference in coronary artery calcium score at 18-month between control and intervention arms [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Singapore

National University Hospital

Singapore, Singapore

Sponsors and Collaborators

National University Health System, Singapore

National Medical Research Council (NMRC), Singapore

Nattopharma ASA

Investigators

• Principal Investigator: Sabrina Wong Peixin Haroon, MD MRCP FAMS; National University Health System

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Haroon SW, Tai BC, Ling LH, Teo L, Davenport A, Schurgers L, Teo BW, Khatri P, Ong CC, Low S, Yeo XE, Tan JN, Subramanian S, Chua HR, Tan SY, Wong WK, Lau TW. Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial. Medicine (Baltimore). 2020 Sep 4;99(36):e21906. doi: 10.1097/MD.0000000000021906.

• Responsible Party: Sabrina Haroon Wong Peixin, Consultant Nephrologist, University Medicine Cluster, National University Health System, Singapore
• ClinicalTrials.gov Identifier: NCT02870829
• Other Study ID Numbers: NHG DSRB Ref: 2015/01000
• First Posted: August 17, 2016
• Last Update Posted: May 5, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data to be shared with collaborators

Additional relevant MeSH terms:

Vitamin K Deficiency; Calcinosis; Vascular Calcification; Calcium Metabolism Disorders; Metabolic Diseases; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Vitamin K 2; Vitamin K; Vitamin MK 7; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants; Vitamins; Micronutrients; Physiological Effects of Drugs