Vitamin K1 to Slow Progression of Vascular Calcification in HD Patients

NCT01742273 | Terminated Phase 3 DMC

• 2 other identifiers: VitaVasK2010-021264-14
• Study Type: interventional
• Target: 63
• Locations: 3 countries
• Sites: 13

Brief Summary

Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular mortality associated with extensive vascular calcification (VC). In the past years the development of VC was discovered to be actively regulated and as being influenced by inhibitors of calcification (e.g. matrix-Gla-protein, fetuin-A). MGP is produced by vascular smooth muscle cells and needs post-translational modification by vitamin K dependent gamma-carboxylation to be fully active. Based on the demonstration of increased PIVKA-II levels, about 97% of all HD patients exhibit insufficient carboxylation activity. We therefore aim in this randomized, controlled study to retard the progress of coronary and aortal calcification as assessed by thoracic multislice-CT by the thrice weekly administration of 5 mg vitamin K1 (phylloquinone) to about 100 HD patients over a period of 18 months.

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• Progression of coronary artery calcification and thoracic aortic calcification

  Progression of coronary artery calcification and thoracic aortic calcification(absolute change of the volume score at the 18-month MSCT versus the baseline MSCT)

  18 months

Secondary Outcomes (4)

• Progression of aortic valve calcification

  18 months

• Progression of mitral valve calcification

  18 months

• Mortality from any cause within 18 months after the treatment

  6 years

• Major adverse cardiovascular events: myocardial infarction, stroke, acute coronary syndrome,embolism, symptom-driven revascularization, death from cardiovascular cause within 18 months after start of treatment

  6 years

Study Arms (2)

standard treatment (usual care)

NO INTERVENTION

standard treatment (usual care)

Vitamin K1

EXPERIMENTAL

Vitamin K1 (phylloquinone), thrice weekly p.o. (5mg)

Drug: Vitamin K1

Interventions

Vitamin K1 DRUG

Vitamin K1 to slow vascular calcification

Also known as: KA-Vit Tropfen (phylloquinone)

Vitamin K1

Eligibility Criteria

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

You may qualify if:

• Male or Female minimum 18 years of age
• Not less than 6 months on hemodialysis
• Cardiovascular calcification percent (coronary artery volume score \> 100)
• Written consent to take part in the study
• Life expectancy not less than 18 months

You may not qualify if:

• Known hypersensitivity against Vitamin K1
• History of thrombosis
• intake of Vitamin K
• tumor disease
• pulse \>100/min (resting heart rate)
• Intake of vitamin K antagonists (e.g. Marcumar) at baseline or in the 3 months prior to baseline
• Inflammatory bowel disease
• Short-bowel syndrome
• Significant liver dysfunction
• more than one stent in one coronary artery plus one or more stents in an additional artery
• Hemoglobin \< 70 g/L
• Women who are pregnant or breastfeeding
• Women without sufficient contraception
• Alcohol or drug abuse
• Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (13)

Université catholique de Louvain - Department of Nephrology

Brussels, Belgium

Location

UZ Leuven, Dept. of Nephrology

Leuven, 3000, Belgium

Location

KfH Curatorship for Dialysis and Renal transplantation e.V.

Aachen, 52074, Germany

Location

University Hospital of RWTH Aachen, Department of Medicine II

Aachen, Germany

Location

Clinical Center of Coburg - Department of Medical Clinic III, Nephrology

Coburg, Germany

Location

MVZ DaVita Düsseldorf

Düsseldorf, 40210, Germany

Location

KfH Curatorchip for Dialysis and Renal Transplantation e.V.

Düsseldorf, Germany

Location

University Hospital Düsseldorf - Department of Nephrology

Düsseldorf, Germany

Location

MVZ Diaverum Erkelenz/ Heinsberg

Erkelenz, Germany

Location

University hospital of Erlangen - Department of Medicine 4, Nephrology and Hypertension

Erlangen, Germany

Location

Internistische Facharztpraxis, Abteilung Kardiologie - Nephrologie, Dialyse Geilenkirchen

Geilenkirchen, 52511, Germany

Location

KfH Curatorchip for Dialysis and Renal Transplantation e.V.

Stolberg, 52222, Germany

Location

University Hospital at Huddings, Karolinska Institute Stockholm - Department of Renal Medicine K56

Stockholm, Sweden

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Vitamin K 1

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Jürgen Floege, Prof. Dr.

  University Hospital of RWTH Aachen -Department of Medicine II, Nephrology and Clinical Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2012
• First Posted: December 5, 2012
• Study Start: October 1, 2013
• Primary Completion: July 17, 2020
• Study Completion: July 17, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

DE (10); BE (2); SE (1)