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Trial record 1 of 1 for:    NCT01528800
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Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients (iPACK-HD)

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ClinicalTrials.gov Identifier: NCT01528800
Recruitment Status : Active, not recruiting
First Posted : February 8, 2012
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Rachel Holden, Clinical Evaluation Research Unit at Kingston General Hospital

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.

Condition or disease Intervention/treatment Phase
End-stage Kidney Disease Drug: Vitamin K1 Drug: Microcrystalline Methylcellulose Phase 2

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?

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Inhibit Progression of Coronary Artery Calcification With Vitamin K in HemoDialysis Patients: The iPACK-HD Study
Study Start Date : November 2012
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Microcrystalline Methylcellulose
Drug: Microcrystalline Methylcellulose
10mg orally three times a week for 12 months

Active Comparator: Vitamin K1
Vitamin K1
Drug: Vitamin K1
10mg orally three times a week for 12 months
Other Names:
  • Phytonadione
  • Phylloquinone




Primary Outcome Measures :
  1. Recruitment rate [ Time Frame: 12 months ]
    i.e. Number of participants recruited per month.

  2. Compliance with study medication [ Time Frame: 12 months ]
    i.e. Proportion of prescribed doses received.

  3. Dropout rate [ Time Frame: 12 months ]
    i.e. Number of participants who drop out from the trial.

  4. Adherence to study protocol [ Time Frame: 12 months ]
    i.e. Proportion of participants who adhere to the study protocol.

  5. Electronic data capture system form completion [ Time Frame: 12 months ]
    i.e. Proportion of required electronic data capture system forms completed successfully.


Secondary Outcome Measures :
  1. Coronary artery calcification (Agatston calcium scores) progression [ Time Frame: 12 months ]
    Agatston calcium scores (CT scans) will be measured at baseline and at 12 months.

  2. Coronary artery calcification (volume calcium scores) progression [ Time Frame: 12 months ]
    Volume calcium scores (CT scans) will be measured at baseline and at 12 months.

  3. Prevalence and incidence of thoracic vertebral fractures [ Time Frame: 12 months ]
    Radiographs of the thoracic spine will be assessed at baseline and at 12 months.

  4. Prevalence and incidence of lumbar vertebral fractures [ Time Frame: 12 months ]
    Radiographs of the lumbar spine will be assessed at baseline and at 12 months.

  5. Hospitalizations [ Time Frame: 12 months ]
  6. Cardiovascular events [ Time Frame: 12 months ]
    Acute coronary syndrome, congestive heart failure, myocardial infarction, stroke, transient ischemic attack, amputation; cardiac, (symptom-driven) cerebral or peripheral revascularization procedure.

  7. Thrombosis [ Time Frame: 12 months ]
    Deep vein thrombosis and pulmonary embolism.

  8. HD access thrombosis [ Time Frame: 12 months ]
    Fistula and/or graft thrombosis or dialysis catheter thrombosis.

  9. Mortality [ Time Frame: 12 months ]
    All-cause and cardiovascular cause .

  10. Phylloquinone [ Time Frame: 12 months ]
  11. PIVKA [ Time Frame: 12 months ]
  12. Osteocalcin [ Time Frame: 12 months ]
  13. MGP [ Time Frame: 12 months ]
  14. Desphospho-carboxylated matrix Gla protein (dpcMGP) [ Time Frame: 12 months ]
  15. Desphospho-uncarboxylated matrix Gla protein (dpucMGP) [ Time Frame: 12 months ]
  16. Thoracic aortic calcification (absolute change of Agatston calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the Agatston calcium scores (CT scan) will be assessed at 12 months vs. baseline.

  17. Thoracic aortic calcification (absolute change of volume calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the volume calcium scores (CT scan) will be assessed at 12 months vs. baseline.

  18. Aortic valve calcification (absolute change of Agatston calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the Agatston calcium scores (CT scan) will be assessed at 12 months vs. baseline.

  19. Aortic valve calcification (absolute change of volume calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the volume calcium scores (CT scan) will be assessed at 12 months vs. baseline.

  20. Mitral valve calcification (absolute change of Agatston calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the Agatston calcium scores (CT scan) will be assessed at 12 months vs. baseline.

  21. Mitral valve calcification (absolute change of volume calcium scores) progression [ Time Frame: 12 months ]
    The absolute change of the volume calcium scores (CT scan) will be assessed at 12 months vs. baseline.


Other Outcome Measures:
  1. C-reactive protein (CRP) [ Time Frame: 12 months ]
  2. Interleukin 6 (IL-6) [ Time Frame: 12 months ]
  3. Fetuin [ Time Frame: 12 months ]
  4. Osteoprotegerin [ Time Frame: 12 months ]
  5. Phosphorus [ Time Frame: 12 months ]
  6. Calcium [ Time Frame: 12 months ]
  7. Parathyroid hormone (PTH) [ Time Frame: 12 months ]
  8. Dosage of phosphorus binders [ Time Frame: 12 months ]
    i.e. Calcium carbonate, calcium acetate, TUMS, sevelamer, Lanthanum, Sucralfate).

  9. Dosage of ergo-calciferol (25(OH) vitamin D) [ Time Frame: 12 months ]
  10. Dosage of vitamin D analogues [ Time Frame: 12 months ]
    i.e. Calcitriol, paricalcitol.

  11. Dosage of lipid lowering medications [ Time Frame: 12 months ]
  12. Dosage of angiotensin converting enzyme inhibitors [ Time Frame: 12 months ]
  13. Dosage of angiotensin receptor blockers [ Time Frame: 12 months ]
  14. Dosage of antihypertensives [ Time Frame: 12 months ]
  15. Dosage of multivitamins [ Time Frame: 12 months ]
  16. Dosage of bisphosphonates [ Time Frame: 12 months ]
  17. Dosage of prednisone [ Time Frame: 12 months ]
  18. Dosage of cholesterol-lowering medications [ Time Frame: 12 months ]
  19. Changes in L3 slice muscle cross-sectional area [ Time Frame: 12 months ]
  20. Changes in L3 slice normalized muscle cross-sectional area [ Time Frame: 12 months ]
  21. Changes in L3 slice intermuscular adipose tissue (IMAT) cross-sectional area [ Time Frame: 12 months ]
  22. Changes in L3 slice visceral adipose tissue (VAT) cross-sectional area [ Time Frame: 12 months ]
  23. Changes in L3 slice subcutaneous adipose tissue (SAT) cross-sectional area [ Time Frame: 12 months ]
  24. Changes in L3 slice total adipose tissue (TAT) cross-sectional area [ Time Frame: 12 months ]
  25. Changes in L3 slice muscle radiodensity [ Time Frame: 12 months ]
  26. Changes in L3 slice intermuscular adipose tissue (IMAT) radiodensity [ Time Frame: 12 months ]
  27. Changes in L3 slice visceral adipose tissue (VAT) radiodensity [ Time Frame: 12 months ]
  28. Changes in L3 slice subcutaneous adipose tissue (SAT) radiodensity [ Time Frame: 12 months ]
  29. Thoracic aortic calcification (Agatston score) progression [ Time Frame: 12 months ]
    Percent of patients with regression of thoracic aortic calcification of at least 10% (Agatston score) will be assessed at 12 months compared to the baseline.

  30. Thoracic aortic calcification (volume) progression [ Time Frame: 12 months ]
    Percent of patients with regression of thoracic aortic calcification of at least 10% (volume) will be assessed at 12 months compared to the baseline.

  31. Coronary artery calcification (Agatston score) progression [ Time Frame: 12 months ]
    Percent of patients with regression of coronary artery calcification (Agatston score) of at least 10% will be assessed at 12 months compared to the baseline.

  32. Coronary artery calcification (volume) progression [ Time Frame: 12 months ]
    Percent of patients with regression of coronary artery calcification (volume) of at least 10% will be assessed at 12 months compared to the baseline.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01528800


Locations
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Canada, Ontario
Kingston Health Sciences Centre: Kingston General Hospital Site
Kingston, Ontario, Canada, K7L 2V7
London Health Sciences Centre
London, Ontario, Canada, N6A 5W9
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
Dr. Rachel Holden
Investigators
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Principal Investigator: Rachel Holden Queens University/Kingston Health Sciences Centre: Kingston General Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr. Rachel Holden, Professor of Medicine Queen's University, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT01528800    
Other Study ID Numbers: iPACK-HD
First Posted: February 8, 2012    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Keywords provided by Dr. Rachel Holden, Clinical Evaluation Research Unit at Kingston General Hospital:
Vitamin K
Chronic Kidney Disease
Vascular Calcification
Hemodialysis
Coronary Artery Calcification
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Calcinosis
Urologic Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Vitamin K
Vitamin K 1
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants