Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K

NCT02870829 | Completed Phase 2 DMC

• 1 other identifier: NHG DSRB Ref: 2015/01000
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Absolute difference in AVC score at 18-months

  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

Study Arms (2)

Vitamin K2

EXPERIMENTAL

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

Standard Therapy

NO INTERVENTION

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

Interventions

menaquinone-7 DRUG

Oral supplement given post dialysis 3x/week

Vitamin K2

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Health System, Singapore: lead
• National Medical Research Council (NMRC), Singapore: collaborator
• Nattopharma ASA: collaborator

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (1)

• 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.

  PMID: 32899022 DERIVED

MeSH Terms

Conditions

Vascular Calcification

Interventions

menaquinone 7

Condition Hierarchy (Ancestors)

Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Sabrina Wong Peixin Haroon, MD MRCP FAMS

  National University Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Nephrologist, University Medicine Cluster

Study Record Dates

• First Submitted: August 14, 2016
• First Posted: August 17, 2016
• Study Start: July 1, 2016
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

SG (1)