Clinical Trial: Vitamin K1 to Slow Progression of Vascular Calcification in HD Patients
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Vitamin K1 to Slow Progression of Vascular Calcification in Hemodialysis Patients
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 a total of 348 HD patients over a period of 18 months.
Detailed Summary:
Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular mortality associated with extensive vascular calcification (VC). This forms - at least partially - the reason for the excessively increased cardiovascular mortality in this population.
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). Matrix Gla protein (MGP) is a powerful vascular wall-based inhibitor of VC. MGP is produced by vascular smooth muscle cells and needs post-translational modification by vitamin K dependent gamma-carboxylation to be fully active. The role of MGP was discovered in knock-out mice, which died from rupture of a massively calcified aorta. Functional vitamin K deficiency induced by administration of warfarin leads to the development of VC, which in turn can be inhibited by subsequent administration of vitamin K1. Warfarin inhibits the vitamin K mediated gamma-carboxylation, which leads to the production of noncarboxylated and inactive MGP (ucMGP).
Warfarin is widely used due to its inhibitory capacity on the activation of coagulation factors. Now it has been discovered that the use of vitamin K inhibitors influences vascular health: long-term use of warfarin is associated with an increased prevalence and extent of VC in the normal population and HD patients. Warfarin is also a crucial risk factor for the development of calciphylaxis, a life-threatening complication in HD patients characterised by calcified cutaneous vessels. In turn, administration of vitamin K1 was accompanied by reduced intima-media-thickness (IMT) and increased elasticity of vessels in postmenopausal women.
Based on the demonstration of increased PIVKA-II levels, about 97% of all HD pat
Sponsor: RWTH Aachen University
Current Primary Outcome: Progression of coronary artery calcification and thoracic aortic calcification [ Time Frame: 18 months ]
Original Primary Outcome:
- Progression of coronary artery calcification [ Time Frame: 18 months ]Progression of coronary artery calcification (absolute change of the volume score at the 18-month MSCT versus the baseline MSCT)
- Progression of thoracic aortic calcification [ Time Frame: 18 months ]Progression of coronary artery calcification (absolute change of the volume score at the 18-month MSCT versus the baseline MSCT)
Current Secondary Outcome:
- Progression of aortic valve calcification [ Time Frame: 18 months ]Progression of aortic valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
- Progression of mitral valve calcification [ Time Frame: 18 months ]Progression of mitral valve calcification (absolute change of the Agatston-Score and volume score at the 18-month MSCT versus the baseline MSCT)
- Mortality from any cause within 18 months after the treatment [ Time Frame: 6 years ]Mortality from any cause within 18 months after the treatment
- 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 [ Time Frame: 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
Original Secondary Outcome:
- Progression of thoracic aortic calcification [ Time Frame: 18 months ]Progression of thoracic aortic calcification (absolute change of the Agatston-Score at the 18-month MSCT)
- Progression of coronary artery calcification [ Time Frame: 18 months ]Progression of coronary artery calcification (absolute change of the Agatston-Score at the 18-month MSCT versus the baseline MSCT)
- Progression of aortic valve calcification [ Time Frame: 18 months ]Progression of aortic valve calcification (absolute change of the Agatston and volume scores at the 18-month MSCT versus the baseline MSCT)
- Progression of mitral valve calcification [ Time Frame: 18 months ]Progression of mitral valve calcification (absolute change of the Agatston and volume scores at the 18-month MSCT versus the baseline MSCT)
- Mortality from any cause within 18 months after the treatment [ Time Frame: 6 years ]Mortality from any cause within 18 months after the treatment
- 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 [ Time Frame: 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
Information By: RWTH Aachen University
Dates:
Date Received: December 3, 2012
Date Started: October 2013
Date Completion: September 2019
Last Updated: September 21, 2015
Last Verified: September 2015
