Effects of Fhytomenadione on Coronary Artery Calcification of Hemodialysis Patients

NCT04247087 | Completed

• 1 other identifier: 1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Calcification

Keywords

coronary calcification; phytomenadione; chronic kidney disease; hemodialysis

Outcome Measures

Primary Outcomes (1)

• coronary calcium score

  Within the population of hemodialysis patients, patients who met the inclusion criteria were sought, once the participation in the study was accepted and an informed consent was signed, a coronary tomography was performed and interpreted by Radiology staff, who had no knowledge about the study groups or their intervention. Those patients who fulfilled the coronary calcification tomographic criterion defined as coronary calcium score of 10 Agatston units were randomized to receive the intervention or the placebo. At the end of the 12 month follow-up, a coronary tomography was performed again to quantify the final Agatston score

  12 months

Secondary Outcomes (1)

• cardiovascular events

  12 months

Study Arms (2)

Intervention group

EXPERIMENTAL

phytomenadione 10 mg (1 vial in the venous line of the extracorporeal hemodialysis circuit) post hemodialysis 3 times a week for 12 months

Drug: phytomenadione

Control group

PLACEBO COMPARATOR

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

Drug: placebo solution

Interventions

phytomenadione DRUG

phytomenadione 10 mg (1 vial in the venous line of the extracorporeal hemodialysis circuit) post hemodialysis 3 times a week for 12 months

Also known as: vitamin K

Intervention group

placebo solution DRUG

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

Also known as: solution for injection

Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with chronic kidney disease in hemodialysis
• Patients who have 6 months or more on hemodialysis
• Patients over 18 years
• Patients that meet the tomographic criterion of a coronary calcium score of 10 Agatston units.

You may not qualify if:

• Patients in previous or current treatment with phytomenadione
• Coronary stent patients
• Patients with arrhythmias and requiring oral anticoagulation with warfarin or acenocoumarin
• Pregnant patients
• Patients who undergo renal transplantation during the follow-up period
• Patients who change the modality to peritoneal dialysis during the follow-up period
• Patients who are known allergy to vitamin K

Sponsors & Collaborators

• Instituto Mexicano del Seguro Social: lead
• Marco Antonio Ocampo Apolonio: collaborator
• Rodolfo Guardado Mendoza: collaborator
• Texar Alfonso Pereyra Nobara: collaborator

Study Sites (1)

Hospital de Alta Especialidad No. 1 Bajío, Boulevard Adolfo López Mateos esquina Insurgentes S/N, colonia Los Paraísos

León, Guanajuato, 37260, Mexico

Location

Related Publications (9)

• National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.

  PMID: 11904577 BACKGROUND

• Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998 Nov;32(5 Suppl 3):S112-9. doi: 10.1053/ajkd.1998.v32.pm9820470. No abstract available.

  PMID: 9820470 BACKGROUND

• Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int. 2007 Mar;71(5):438-41. doi: 10.1038/sj.ki.5002059. Epub 2007 Jan 3.

  PMID: 17200680 BACKGROUND

• Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000 May 18;342(20):1478-83. doi: 10.1056/NEJM200005183422003.

  PMID: 10816185 BACKGROUND

• Longenecker JC, Coresh J, Powe NR, Levey AS, Fink NE, Martin A, Klag MJ. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study. J Am Soc Nephrol. 2002 Jul;13(7):1918-27. doi: 10.1097/01.asn.0000019641.41496.1e.

  PMID: 12089389 BACKGROUND

• Pilkey RM, Morton AR, Boffa MB, Noordhof C, Day AG, Su Y, Miller LM, Koschinsky ML, Booth SL. Subclinical vitamin K deficiency in hemodialysis patients. Am J Kidney Dis. 2007 Mar;49(3):432-9. doi: 10.1053/j.ajkd.2006.11.041.

  PMID: 17336705 BACKGROUND

• Oikonomaki T, Papasotiriou M, Ntrinias T, Kalogeropoulou C, Zabakis P, Kalavrizioti D, Papadakis I, Goumenos DS, Papachristou E. The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial. Int Urol Nephrol. 2019 Nov;51(11):2037-2044. doi: 10.1007/s11255-019-02275-2. Epub 2019 Sep 17.

  PMID: 31529295 RESULT

• Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. doi: 10.1093/jn/134.11.3100.

  PMID: 15514282 RESULT

• Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, Kaczmarska M, Stefanczyk L, Vermeer C, Maresz K, Nowicki M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol Arch Med Wewn. 2015;125(9):631-40. doi: 10.20452/pamw.3041. Epub 2015 Jul 15.

  PMID: 26176325 RESULT

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Vitamin K 1; Vitamin K; Solutions; Injections

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Hilda E Macias Cervantes, Doctor

  Instituto Mexicano del Seguro Social

  PRINCIPAL INVESTIGATOR

• Marco A Ocampo Apolonio, Doctor

  Instituto Mexicano del Seguro Social

  STUDY CHAIR

• Rodolfo Guardado Mendonza, Doctor

  Universidad de Guanajuato

  STUDY DIRECTOR

• Texar A Pereyra Nobara, Doctor

  Instituto Mexicano del Seguro Social

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients were randomly assigned to receive intravenous vitamin K or placebo solution. Coronary tomography was performed and interpreted by Radiology staff, who had no knowledge about the study groups or their intervention
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: randomized clinical trial with double blinding compared to placebo

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: January 29, 2020
• Study Start: September 7, 2017
• Primary Completion: September 27, 2019
• Study Completion: January 2, 2020
• Last Updated: January 29, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)