Clinical trial NCT02870829: Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vascular Calcification
Systemic and Arterial Stiffness
Complication of Hemodialysis
Deficiency of Vitamin K2
Lead sponsor: National University Health System, Singapore
Sponsor class: OTHER
Collaborators: name: National Medical Research Council (NMRC), Singapore
name: Nattopharma ASA
First posted: 2016-08-17
Enrollment: 178
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Absolute difference in coronary artery calcium score at 18-month between control and intervention arms
timeFrame: 18 months
Secondary outcomes:
measure: Absolute difference in AVC score at 18-months
timeFrame: 18 months
measure: Percentage of patients with regression of CAC of ≥ 10% over 18-month
timeFrame: 18 months
measure: Absolute difference in cfPWV and AI at 18-months
timeFrame: 18 months
measure: Mortality from any cause within the study period
timeFrame: 18 months
measure: MACE defined as non-fatal myocardial infarction, heart failure, acute coronary syndrome, need for coronary revascularization, non-fatal stroke, significant peripheral vascular disease
timeFrame: 18 months
measure: Difference in plasma levels of dp-ucMGP at 18 months
timeFrame: 18 months
measure: 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
timeFrame: 18 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Health System
name: Sabrina Wong Peixin Haroon, MD MRCP FAMS
role: PRINCIPAL_INVESTIGATOR
References:
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.