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End-stage Kidney DiseasePhase 2iPACK-HDNCT01528800

Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients

A Phase 2 study testing Vitamin K1 and Microcrystalline Methylcellulose in people with End-stage Kidney Disease, run by Dr. Rachel Holden at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
End-stage Kidney Disease
What is being tested?
Vitamin K1 and Microcrystalline Methylcellulose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
85 participants
Where
3 sitesCanada
Study dates
Nov 2012to Dec 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Kingston Health Sciences Centre: Kingston General Hospital Site

    Kingston, Ontario, K7L 2V7

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • The Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

Other trials in Canada

About this study

Official title: Inhibit Progression of Coronary Artery Calcification With Vitamin K in HemoDialysis Patients: The iPACK-HD Study

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.

Read the 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?

Being tested
Vitamin K1, Microcrystalline Methylcellulose
Keywords
Vitamin K, Chronic Kidney Disease, Vascular Calcification, Hemodialysis, Coronary Artery Calcification
Medical subject headings
Kidney Failure, Chronic, Renal Insufficiency, Chronic, Vascular Calcification

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vitamin K1Drug

    Also called Phytonadione, Phylloquinone

    10mg orally three times a week for 12 months

  • Microcrystalline MethylcelluloseDrug

    10mg orally three times a week for 12 months

Study groups in NCT01528800
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMicrocrystalline Methylcellulose
Receives: Drug: Microcrystalline Methylcellulose
Vitamin K1Active comparatorVitamin K1
Receives: Drug: Vitamin K1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recruitment rate

    Number of participants recruited per month at each site) and an overall crude average of each site's rate.

    Measured: 12 months

  2. Compliance with study medication

    Proportion of prescribed doses received.

    Measured: 12 months

  3. Dropout rate

    Proportion of participants who dropped out from the trial.

    Measured: 12 months

  4. Adherence to study protocol

    Proportion of participants who adhered to the study protocol.

    Measured: 12 months

  5. Rates of eligible patients consented and randomized

    Proportion of eligible patients consented and randomized.

    Measured: 12 months

Secondary outcomes (17)

  1. Coronary artery calcification (Agatston calcium scores) progression

    A)The percent and absolute change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline. Included measures will be: Total CAC, Left Main CAC, Right Coronary Artery CAC, Left Anterior Descending CAC, Circumflex CAC, and Posterior Descending Artery CAC.

    1. The proportion of participants with a 15% or greater increase in Agatston calcium scores will be assessed at study exit vs baseline.

    Measured: 12 months

  2. Coronary artery calcification (volume calcium scores) progression

    1. The percent and absolute change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline. Included measures will be: Total CAC, Left Main CAC, Right Coronary Artery CAC, Left Anterior Descending CAC, Circumflex CAC, and Posterior Descending Artery CAC.
    2. The proportion of participants with a 15% or greater increase in volume calcium scores will be assessed at study exit vs baseline.

    Measured: 12 months

  3. Coronary artery calcification (Agatston calcium scores) regression

    The proportion of participants with a 10% or greater decrease in Agatston calcium scores will be assessed at study exit vs baseline.

    Measured: 12 months

  4. Coronary artery calcification (volume calcium scores) regression

    The proportion of participants with a 10% or greater decrease in volume calcium scores will be assessed at study exit vs baseline.

    Measured: 12 months

  5. Aortic valve calcification (Agatston calcium scores) progression

    The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.

    Measured: 12 months

  6. Aortic valve calcification (volume calcium scores) progression

    The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.

    Measured: 12 months

  7. Mitral valve calcification (Agatston calcium scores) progression

    The absolute and percentage change of the Agatston calcium scores (CT scan) will be assessed at study exit vs. baseline.

    Measured: 12 months

  8. Mitral valve calcification (volume calcium scores) progression

    The absolute and percentage change of the volume calcium scores (CT scan) will be assessed at study exit vs. baseline.

    Measured: 12 months

  9. Abdominal aortic calcification (AAC) scores

    The AAC score (mean score in L1-L4, mean number of positive segments, mean total severity using lateral lumbar spine radiographs) will be assessed at study exit vs. baseline.

    Measured: 12 months

  10. Levels of biomarkers of vitamin K status

    Gas6, PK, MK4, osteocalcin Gla, osteocalcin Glu, osteocalcin Gla to Glu ratio, percent of osteocalcin undercarboxylated, and dpucMGP will be assessed at baseline, four, eight and study exit. Protein induced by vitamin K absence or antagonist II (PIVKA-II) will be assessed at baseline and study exit.

    Measured: 12 months

  11. Prevalence and incidence of thoracic vertebral fractures

    The prevalence and incidence of thoracic vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.

    Measured: 12 months

  12. Prevalence and incidence of lumbar vertebral fractures

    The prevalence and incidence of lumbar vertebral fractures (anterior and lateral radiographs) will be assessed at baseline and study exit.

    Measured: 12 months

  13. Presence/absence and total hospitalizations

    The presence or absence and total hospitalizations will be assessed across the study duration per patient.

    Measured: 12 months

  14. Presence/absence and total cardiovascular events

    The presence or absence and total cardiovascular events (acute coronary syndrome, congestive heart failure, stroke, transient ischemic attack, amputation, and cardiac [symptom-driven] [cerebral or peripheral] revascularization procedure, or cardiac arrest) will be assessed across the study duration per patient.

    Measured: 12 months

  15. Presence/absence and total thrombotic events

    The presence or absence and total thrombotic events (deep vein thrombosis and pulmonary embolism) will be assessed across the study duration per patient.

    Measured: 12 months

  16. Presence/absence and total hemodialysis access thrombotic events

    The presence or absence and total hemodialysis access thrombotic events (fistula and/or graft thrombosis or dialysis catheter thrombosis) will be assessed across the study duration per patient.

    Measured: 12 months

  17. Presence/absence and total mortality

    The presence or absence and total all-cause and cardiovascular cause mortality will be assessed across the study duration per patient.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionDec 2019
  4. Study completionDec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01528800
Sponsor's protocol ID
iPACK-HD
Acronym
iPACK-HD
Status last verified
Jun 2021
First submitted
6 Feb 2012
Last updated
28 Jun 2021
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 35641194

  • 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.

    PubMed 26075081

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vitamin K1 and Microcrystalline Methylcellulose in people with End-stage Kidney Disease, run by Dr. Rachel Holden at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recruitment rate (time frame: 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01528800, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2021.

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