Aortic Calcification and Vitamin K Antagonists

Vascular Calcification Clinical Trial

— AVKAL  

Official title:

Aortic Calcification and Vitamin K Antagonists

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02823093
• Other study ID #: PI2015_843_0025
• Status: Recruiting
• Phase: N/A
• First received: April 25, 2016
• Last updated: January 30, 2017
• Start date: April 2016
• Est. completion date: April 2017

Study information

• Verified date: January 2017
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: Sophie Liabeuf, Dr
• Email: liabeuf.sophie[@]chu-amiens.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The vitamin K antagonists (VKA) are necessary drugs of prevention and treatment of thrombo-embolic disease. The AVKAL study assesses the impact of VKA treatment on the aortic calcifications development. This is a biomedical research without health product, transversal and monocentric study which compares the aortic calcifications levels of two populations : one treated by VKA and the other which has never been treated by VKA.

Description:

The vitamin K antagonists exercise their anticoagulant effect by preventing the vitamin K dependant gamma-carboxylation of coagulation II, VII, IX and X factors which forms the final step of their activation.

They inhibit the vitamin K epoxide reductase VKORC1 enzyme, which is responsible of the vitamin K epoxide recycling in vitamin K hydroquinone (its reduced form). The carboxylation also can be inhibited by the Matrix Gla protein (MGP), inhibitor factor of vascular calcifications.

Warfarin (the most used VKA at the word level) is employed on animal for produce vascular calcifications by inhibiting the MGP activation.

Epidemiologic data indicate that warfarin could increase the calcifications of cardiac valves and coronary arteries. However, these studies were not interested in abdominal aorta's calcifications which are considered like an important marker of cardiovascular risk and did not concern the fluindione which is the most used VKA in France. Even if a class effect seems logical, the investigators can't dismiss the local effects, different to warfarin. In these studies, the calcifications assessment were rarely quantitative and the MGP levels were not measured. The vascular calcifications constitute a potential adverse effect of VKA which could limit their benefit in certain populations.

In this work there is an assumption that the aortic calcifications levels are upper in patients receiving VKA than in patients who are not receiving VKA and the aortic calcifications increase is owed to the non-activation of MGP.

The main objective is to assess if the taking of VKA is associated with the aortic calcifications development in patients receiving VKA.

Investigators will compare 2 populations: one group treated by VKA treatment for at least 6 months and one focus group which have never been treated by VKA treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 338
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients having a abdominal scanner without injection planned at CHU Amiens

• group treated by VKA: VKA treatment for at least 6 months

• group not treated by VKA: no antecedent of AVK treatment

Exclusion Criteria:

• abdominal scanner contre indication

• progressive cancer

• scanner planned by emergency department

• patient having had acute cardiovascular accident in the last 3 months

Related Conditions & MeSH terms

• Calcinosis
• Vascular Calcification

Locations

Country	Name	City	State
France	CHU Amiens	Amiens

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

References & Publications (4)

Price PA, Faus SA, Williamson MK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1400-7. — View Citation

Price PA, Urist MR, Otawara Y. Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem Biophys Res Commun. 1983 Dec 28;117(3):765-71. — View Citation

Schurgers LJ, Aebert H, Vermeer C, Bültmann B, Janzen J. Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood. 2004 Nov 15;104(10):3231-2. — View Citation

Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calcifications scores	Agatston's method	at inclusion
Secondary	Plasmatic concentrations in dp-ucMGP	The first measure of MGP is actually a measure of the dephosphorylated MGP [ dpMGP ] performed by ELISA	12 months