Effect on Vascular Calcification of Replacing Warfarin by Rivaroxaban With or Without VitK2 in Hemodialysis Patients

What Was Tested

In this phase 4 trial, researchers set out to test Vitamin D, K2, Magnesium and Zinc.

This study examines patients on chronic hemodialysis with non-valvular atrial fibrillation, who have a CHA2DS2-VASc Score of ≥ 2 and therefore are candidates for or already receive a vitamin K antagonist.

The first question is whether replacement of the vitamin K antagonist by rivaroxaban is able to slow progression of vascular calcification.

The second question is whether addition of vitamin K2 to rivaroxaban can further slow down or even halt the progression of vascular calcification.

It had three arms (groups): Vitamin K antagonist (no intervention), rivaroxaban (active comparator) and rivaroxaban and vitamin K2 (active comparator).

Vitamin K antagonist treatment targeting an international normalized ratio of 2 to 3 for 18 months.

The registry classes the interventions as dietary supplement and drug.

More on the Plan

The present study targets dialysis patients with non-valvular atrial fibrillation requiring treatment with vitamin K antagonists.

It addresses the question whether replacement of the vitamin K antagonist by rivaroxaban is able to slow progression of vascular calcification (VC).

Two non-invasive methods are used to evaluate the impact of interventions on the progression of VC: i.e. coronary artery calcification (CAC) and pulse wave velocity (PWV) measurements.

The detection of CAC is predictive for the presence of obstructive coronary artery disease and future coronary events.

Who Took Part

The registry lists 117 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: End stage renal failure treated with chronic hemodialysis. CHA2DS2-VASc Score ≥ 2. Ability to provide informed consent.

The full record lists 4 inclusion and 8 exclusion criteria; among the exclusions: known intestinal malabsorption or inability to take oral medication; inability to stop co-medication that causes major interactions with rivaroxaban (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, ritonavir, rifampicin, phenytoin, carbamazepine, phenobarbital or st john's wort); investigator's assessment that the subject's life expectancy is less than 1 year.

How the Study Was Run

The set-up was randomized, parallel-group and open-label.

The participants were allocated by chance, so the Vitamin D, K2, Magnesium and Zinc group and the comparison group should start out alike.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Everyone knew when Vitamin D, K2, Magnesium and Zinc was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2015-11 with completion listed for 2019-01-23.

It ran at 1 site in Belgium.

Its stated primary purpose is prevention.

What Was Measured

The main thing measured (primary outcome): absolute and relative change in coronary artery calcification score (time frame: 18 months). absolute and relative change in thoracic aortic calcification score (time frame: 18 months). absolute and relative change in pulse wave velocity (time frame: 18 months).

It also tracked 8 secondary outcomes, for example absolute and relative change in aortic valve calcification score, absolute and relative change in mitral valve calcification score, mortality from any cause and Systemic embolism, defined as an acute vascular occlusion of a limb or organ documented by imaging, surgery, or autopsy.

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Vitamin D, K2, Magnesium and Zinc in 117 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Vitamin D, K2, Magnesium and Zinc compound page, all human trials.