NCT04247087

Effects of Fhytomenadione on Coronary Artery Calcification of Hemodialysis Patients

Completed NA Last updated 29 January 2020

What this trial tests

NA trial testing phytomenadione in Coronary Calcification in 60 participants. Completed in 2 January 2020.

Timeline

7 September 2017

Primary endpoint
27 September 2019

2 January 2020

Quick facts

Lead sponsor	Instituto Mexicano del Seguro Social
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	60
Start date	7 September 2017
Primary completion	27 September 2019
Estimated completion	2 January 2020
Sites	1 location across Mexico

Drugs / interventions tested

• phytomenadione — full drug profile →
• placebo solution

Conditions studied

• Coronary Calcification — all drugs for Coronary Calcification →

Sponsor

Instituto Mexicano del Seguro Social — full company profile →

Who can join

Adults 18 to 70, any sex, with Coronary Calcification. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Until 2013 the reported incidence of chronic kidney disease varied widely between countries, reporting the highest prevalence Taiwan, the region of Jalisco in Mexico and United States, with 458, 421 and 363 individuals per million inhabitants respectively. Mexico has around 52,000 patients in replacement therapies, of which 80% of patients are treated in the Instituto Mexicano del Seguro Social (IMSS).

In each stage of renal disease the principal cause of mortality is cardiovascular disease. The risk of cardiovascular mortality is greater than the general population. Arterial calcification, a marker of atherosclerosis and cardiovascular mortality predictor is common in chronic kidney disease. The presence of arterial calcification leads to an increase in arterial stiffness and to a decrease in coronary perfusion resulting in cardiac hypertrophy and myocardial ischemia.

The presence of traditional cardiovascular risk factors like diabetes, hypertension, hyperlipidemia and old age cannot fully explain the high prevalence of atherosclerosis and arterial calcification in chronic kidney disease. Another specific factors related to chronic kidney disease, like hyperphosphatemia, high calcium concentration in dialysis solutions, use of high doses of vitamin D for the management of hyperparathyroidism has been shown to positively influence development of arterial calcification. Invitro studies show that in presence of hyperphosphatemia smooth muscle cells are transformed into osteoblast-like cells that can express proteins that regulate mineralization. Two of this proteins, the matrix Gla protein (MGP) and osteocalcin (OC) are regulators of tissue mineralization in arterial walls and bones respectively. Vitamin K is required as cofactor in the gamma-carboxylation process of several extracellular matrix proteins, converting inactive carboxylated proteins to carboxylated active proteins. Prothrombin and coagulation factors 7,9 y 10 require vitamin K2 for its carboxylation process, while osteocalcin and the matrix Gal protein require vitamin K1. Matrix Gla protein is a calcification inhibitor that plays an important role in the prevention of arterial calcification. For carboxylation and correct function of the MGP is necessary an enzymatic cofactor, vitamin K; this is corroborated in the fact that the antagonism of vitamin K with warfarin antagonizes the carboxylation of MGP and produces rapid arterial calcification.

There are currently no studies evaluating vitamin K in the prevention of vascular calcification in patients with chronic kidney disease, therefore, the role of vitamin K in the patient with kidney disease needs to be clarified with randomized controlled studies, in which the target will be this population of patients at high risk. The aim of this study is evaluate the effect of phytomenadione on coronary artery calcification of patients on hemodialysis compared to placebo, our research hypothesis is that phytomenadione slows the progression and favors the regression of coronary arterial calcification in patients on hemodialysis compared to placebo, evaluating the coronary calcium score by coronary tomography. As secondary objectives was determine changes in the baseline coronary calcium score and at 12 months of use of phytomenadione and presence of cardiovascular events like acute myocardial infarction, unstable angina and death of cardiac cause. The intervention group received phytomenadione 10 mg (1 vial in the venous line of the extracorporeal hemodialysis circuit) post hemodialysis 3 times a week for 12 months and the control group 1 vial of placebo solution (solution for injection in the venous line of the extracorporeal hemodialysis circuit) post hemodialysis 3 times a week for 12 months. The follow-up of the patients was for 12 months, at the end of the follow-up, a coronary control tomography was performed by the Radiology Department to assess the final calcium score. Relative risk measurement (RR), absolute risk reduction (ARR) and number to be treated (NTT) were performed.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial.
   Macias-Cervantes HE, Ocampo-Apolonio MA, Guardado-Mendoza R, Baron-Manzo M, et al · · 2025 · cited 2× · PMID 39680321 · DOI 10.1007/s40620-024-02154-9