What is the clinical evidence from this study?

Study design: RCT. Population: End-stage kidney disease (ESKD) requiring hemodialysis (n=86). Intervention: Phylloquinone vs. Placebo. Primary outcome: Feasibility (recruitment rate, medication compliance, study completion, and protocol adherence).

May 31, 2022Open Access

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial

Key Result

Phylloquinone treatment in hemodialysis patients met predefined feasibility criteria with 96% medication compliance and 80% study completion, but did not significantly reduce the absolute progression of coronary artery calcification compared to placebo.

Study Design

Type

RCT (n=86)

Blinding

Double-blind

Randomization

1:1 stratified by study center and diabetes mellitus

Multicenter

Yes

Structured PICO

Does phylloquinone 10 mg thrice weekly modify coronary artery calcification progression and improve vitamin K status in hemodialysis patients with CAC ≥30 Agatston Units?

Population

86 patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units

Intervention

Phylloquinone 10 mg three times per week for 12 months

Comparator

Matching placebo three times per week for 12 months

Outcome

Feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol)surrogate

A pilot trial of phylloquinone in hemodialysis patients demonstrated feasibility and improved vitamin K status, but showed no difference in coronary artery calcification progression over 12 months.

Limitations

Lack of race or ethnic diversity
CAC outcome could not be assessed in 20% of patients due to death and loss to follow-up
Short observation period of 12 months
Underpowered to detect differences in calcification progression or clinical outcomes

Abstract

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

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