Back to results

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

Primary Purpose

Vascular Calcification, Systemic and Arterial Stiffness, Complication of Hemodialysis

Status

Completed

Phase

Phase 2

Locations

Singapore

Study Type

Interventional

Intervention

menaquinone-7

About this trial

This is an interventional treatment trial for Vascular Calcification

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Vitamin K2

Standard Therapy

Arm 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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Percentage of patients with regression of CAC of ≥ 10% over 18-month

Absolute difference in cfPWV and AI at 18-months

Mortality from any cause within the study period

MACE defined as non-fatal myocardial infarction, heart failure, acute coronary syndrome, need for coronary revascularization, non-fatal stroke, significant peripheral vascular disease

Difference in plasma levels of dp-ucMGP at 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

Full Information

NCT ID

NCT02870829

First Posted

August 14, 2016

Last Updated

January 13, 2023

Sponsor

National University Health System, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore, Nattopharma ASA

1. Study Identification

Unique Protocol Identification Number

NCT02870829

Brief Title

Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K

Acronym

TReVasc-HDK

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

July 2016 (Actual)

Primary Completion Date

February 2022 (Actual)

Study Completion Date

February 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National University Health System, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore, Nattopharma ASA

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

178 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vitamin K2

Arm Type

Experimental

Arm Description

Arm Title

Standard Therapy

Arm Type

No Intervention

Arm 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

Intervention Type

Drug

Intervention Name(s)

menaquinone-7

Intervention Description

Oral supplement given post dialysis 3x/week

Primary Outcome Measure Information:

Title

Absolute difference in coronary artery calcium score at 18-month between control and intervention arms

Description

Comparison made using the t-test following log transformation. Adjustment for baseline CAC scores made via the analysis of covariance.

Time Frame

18 months

Secondary Outcome Measure Information:

Title

Absolute difference in AVC score at 18-months

Description

Comparison made using the t-test following log transformation. Adjustment for baseline AVC scores made via the analysis of covariance.

Time Frame

18 months

Title

Percentage of patients with regression of CAC of ≥ 10% over 18-month

Time Frame

18 months

Title

Absolute difference in cfPWV and AI at 18-months

Time Frame

18 months

Title

Mortality from any cause within the study period

Time Frame

18 months

Title

MACE defined as non-fatal myocardial infarction, heart failure, acute coronary syndrome, need for coronary revascularization, non-fatal stroke, significant peripheral vascular disease

Time Frame

18 months

Title

Difference in plasma levels of dp-ucMGP at 18 months

Time Frame

18 months

Title

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

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sabrina Wong Peixin Haroon, MD MRCP FAMS

Organizational Affiliation

National University Health System

Official's Role

Principal Investigator

Facility Information:

Facility Name

National University Hospital

City

Singapore

Country

Singapore

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data to be shared with collaborators

Citations:

PubMed Identifier

32899022

Citation

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.

Results Reference

derived

Learn more about this trial

Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K

We'll reach out to this number within 24 hrs