VItamin K In PEritonial DIAlysis (VIKIPEDIA): Rationale and study protocol for a randomized controlled trial

Stefanos Roumeliotis, Athanasios Roumeliotis, Panagiotis I Georgianos, Elias Thodis, Leon J Schurgers, Katarzyna Maresz, Theodoros Eleftheriadis, Evangelia Dounousi, Giovanni Tripepi, Francesca Mallamaci, Vassilios Liakopoulos, Stefanos Roumeliotis, Athanasios Roumeliotis, Panagiotis I Georgianos, Elias Thodis, Leon J Schurgers, Katarzyna Maresz, Theodoros Eleftheriadis, Evangelia Dounousi, Giovanni Tripepi, Francesca Mallamaci, Vassilios Liakopoulos

Abstract

Vascular calcification (VC) is an active process, resulting from the disturbance of balance between inhibitors and promoters of calcification, in favor of the latter. Matrix Gla Protein, a powerful inhibitor of VC, needs vitamin K to become active. In vitamin K depletion, plasma levels of the inactive form of MGP, dephosphorylated, uncarboxylated MGP (dp-ucMGP) are increased and associated with VC and cardiovascular (CV) outcomes. End Stage Renal Disease (ESRD) patients have increased circulating dp-ucMGP levels and accelerated VC. VItamin K In PEritoneal DIAlysis (VIKIPEDIA) is a prospective, randomized, open label, placebo-controlled trial, evaluating the effect of vitamin K2 supplementation on arterial stiffness and CV events in ESRD patients undergoing peritoneal dialysis (PD). Forty-four PD patients will be included in the study. At baseline, dp-ucMGP and pulse-wave velocity (PWV) will be assessed and then patients will be randomized (1:1 ratio) to vitamin K (1000 μg MK-7/day) or placebo for 1.5 years. The primary endpoint of this trial is the change in PWV in the placebo group as compared to the treatment group. Secondary endpoints are the occurrence of CV events, mortality, changes in PD adequacy, change in 24-hour ambulatory blood pressure indexes and aortic systolic blood pressure and changes in calcium/phosphorus/parathormone metabolism. VIKIPEDIA is a new superiority randomized, open label, placebo-controlled trial aiming to determine the effect of vitamin K2 supplementation on VC, CV disease and calcium/phosphorus metabolism, in PD patients. Trial registration: The protocol of this study is registered at ClinicalTrials.gov with identification number NCT04900610 (25 May 2021).

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Leon J. Schurgers received institutional grants from Bayer, Boehringer Ingelheim, NattoPharma, and Immuno Diagnostic Systems (IDS, but this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. SPIRIT schedule of enrolment, interventions,…
Fig 1. SPIRIT schedule of enrolment, interventions, and assessments of the VIKIPEDIA study.

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