Clinical trial NCT01528800: Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients
Official title: Inhibit Progression of Coronary Artery Calcification With Vitamin K in HemoDialysis Patients: The iPACK-HD Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End-stage Kidney Disease
Keywords: Vitamin K
Chronic Kidney Disease
Vascular Calcification
Hemodialysis
Coronary Artery Calcification
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
First posted: 2012-02-08
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see if vitamin K supplementation three times per week reduces the progression of coronary artery calcification over 12 months in dialysis patients compared to placebo.

Detailed description: At every stage of chronic kidney disease (CKD), the leading cause of mortality is cardiovascular disease. This is due, in part, to vascular calcification (VC) of the coronary arteries. The extent of VC in the coronary arteries of patients with CKD is commonly determined by high resolution CT scan. The total coronary artery calcium (CAC) score, measured in Agatston units (AUs), reflects the calcium burden in the three major coronary arteries and is the current standard for determining extent of vascular calcification in hemodialysis patients. Matrix Gla protein (MGP), a vitamin K dependent protein, is a key inhibitor of vascular calcification and is present in the arterial wall. It is established that MGP becomes up-regulated adjacent to sites of calcification and that vitamin K is critical to its function. Therefore vitamin K status may be critical to the extent of vascular calcification in this patient group. However, to date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with kidney failure, a group in which high risk has been established. Therefore, our primary research question is: Does vitamin K supplementation with 10 mg of phylloquinone thrice weekly reduce the progression of coronary artery calcification (as measured by CAC score) over 12 months in prevalent hemodialysis patients with a baseline CAC score of ≥ 30 Agatston Units compared to placebo?

Eligibility criteria: Inclusion Criteria:

* Able to provide signed informed consent
* ≥18 years of age
* Expected to survive one year
* Have end-stage kidney disease and require hemodialysis
* Have a baseline coronary artery calcification score ≥30 Agatston units (AUs)

Exclusion Criteria:

* Have a medical condition that requires warfarin
* Require hemodialysis for acute kidney injury
* Are Pregnant
* Have other severe co-morbid conditions (e.g. malignancy, disabling stroke) with life expectancy less than one year
* Have undergone coronary artery bypass grafting or have stents placed in their coronary arteries
* Are currently enrolled in another interventional trial

Primary outcomes:
measure: Recruitment rate
timeFrame: 12 months
measure: Compliance with study medication
timeFrame: 12 months
measure: Dropout rate
timeFrame: 12 months
measure: Adherence to study protocol
timeFrame: 12 months
measure: Rates of eligible patients consented and randomized
timeFrame: 12 months
Secondary outcomes:
measure: Coronary artery calcification (Agatston calcium scores) progression
timeFrame: 12 months
measure: Coronary artery calcification (volume calcium scores) progression
timeFrame: 12 months
measure: Coronary artery calcification (Agatston calcium scores) regression
timeFrame: 12 months
measure: Coronary artery calcification (volume calcium scores) regression
timeFrame: 12 months
measure: Aortic valve calcification (Agatston calcium scores) progression
timeFrame: 12 months
measure: Aortic valve calcification (volume calcium scores) progression
timeFrame: 12 months
measure: Mitral valve calcification (Agatston calcium scores) progression
timeFrame: 12 months
measure: Mitral valve calcification (volume calcium scores) progression
timeFrame: 12 months
measure: Abdominal aortic calcification (AAC) scores
timeFrame: 12 months
measure: Levels of biomarkers of vitamin K status
timeFrame: 12 months
measure: Prevalence and incidence of thoracic vertebral fractures
timeFrame: 12 months
measure: Prevalence and incidence of lumbar vertebral fractures
timeFrame: 12 months
measure: Presence/absence and total hospitalizations
timeFrame: 12 months
measure: Presence/absence and total cardiovascular events
timeFrame: 12 months
measure: Presence/absence and total thrombotic events
timeFrame: 12 months
measure: Presence/absence and total hemodialysis access thrombotic events
timeFrame: 12 months
measure: Presence/absence and total mortality
timeFrame: 12 months
Other outcomes:
measure: Levels of biomarkers of inflammation
timeFrame: 12 months
measure: Levels of clinical lab values
timeFrame: 12 months
measure: Concomitant medication assessment (presence/absence/dosage)
timeFrame: 12 months
measure: Changes in body composition measures
timeFrame: 12 months
measure: Levels of vascular inflammation variables
timeFrame: 12 months
measure: Levels of vitamin D metabolites
timeFrame: 12 months
Locations:
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre: Kingston General Hospital Site
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: Queens University/Kingston Health Sciences Centre: Kingston General Hospital
name: Rachel Holden
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holden RM, Booth SL, Zimmerman D, Moist L, Norman PA, Day AG, Menard A, Fu X, Shea MK, Babiolakis CS, Nolan R, Turner ME, Ward E, Kaufmann M, Adams MA, Heyland DK. Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial. Nephrol Dial Transplant. 2023 Feb 28;38(3):746-756. doi: 10.1093/ndt/gfac191.
citation: Holden RM, Booth SL, Day AG, Clase CM, Zimmerman D, Moist L, Shea MK, McCabe KM, Jamal SA, Tobe S, Weinstein J, Madhumathi R, Adams MA, Heyland DK. Inhibiting the progression of arterial calcification with vitamin K in HemoDialysis patients (iPACK-HD) trial: rationale and study design for a randomized trial of vitamin K in patients with end stage kidney disease. Can J Kidney Health Dis. 2015 May 1;2:17. doi: 10.1186/s40697-015-0053-x. eCollection 2015.