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The Aortic Valve DECalcification (AVADEC) Trial (AVADEC)

Primary Purpose

Aortic Valve Stenosis, Multidetector Computed Tomography, Vitamin K 2

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).
Placebo
Sponsored by
Axel Diederichsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Aortic Valve Stenosis

Eligibility Criteria

65 Years - 75 Years (Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Participants in the Danish Cardiovascular Screening Trial (Trials. 2015 Dec 5;16:554) with an aortic valve calcification score above 300, but without aortic valve stenosis are eligible.

Exclusion Criteria:

  • Known aortic valve disease (peak velocity ≥3.0 m/s)
  • History of venous thrombosis or other coagulation disorders or use of vitamin K antagonists
  • Disorders of calcium and phosphate metabolism
  • A life-expectancy < 5 years

Sites / Locations

  • Department of Cardiology, Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Placebo

Arm Description

Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day)

Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size.

Outcomes

Primary Outcome Measures

Aortic valve calcification
The primary endpoint is the change in aortic valve calcification. The natural history of the aortic valve calcification is not adequately understood, and accordingly the changes are analyzed in two prespecified patient subgroups (AVC score 300-599 and ≥600, respectively).

Secondary Outcome Measures

Arterial calcification
Change in compiled arterial calcification by non-contrast CT
Aortic size
Change in aortic diameter
Coronary plaque composition
Change in total plaque burden in the coronaries and carotid arteries by contrast CT
Aortic valve area
Change in aortic valve area by transthoracic echocardiography
Bone mineral density
Change in bone mineral density as quantitative CT of the columna lumbalis and hip region
Biomarkers of calcification
Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc).
Quality of life
Change in quality of life

Full Information

First Posted
August 2, 2017
Last Updated
September 28, 2022
Sponsor
Axel Diederichsen
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1. Study Identification

Unique Protocol Identification Number
NCT03243890
Brief Title
The Aortic Valve DECalcification (AVADEC) Trial
Acronym
AVADEC
Official Title
The Effects of Menaquinone-7 Supplementation in Patients With Aortic Valves Calcification
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
January 12, 2018 (Actual)
Primary Completion Date
May 1, 2021 (Actual)
Study Completion Date
May 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Axel Diederichsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Aortic stenosis is a common heart valve disease and due to the growing elderly population the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed, thus presently the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). The investigators hypothesize that MK-7 supplementation will slow down the calcification process.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis, Multidetector Computed Tomography, Vitamin K 2, Randomised Clinical Trial

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomized 1:1 after stratification for site, AVC score (300-599 or ≥600) and statin-use. Each site will be provided with sequentially numbered, opaque and sealed envelopes containing randomly generated treatment allocations. Four different types of envelopes are provided; 1) AVC 300-599, no statin-use; 2) AVC 300-599, statin-use; 3) AVC ≥600, no statin-use; and 4) AVC ≥600, statin-use.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The randomization-list is available to the data and safety monitoring board, but patients, nurses, physicians and other data collectors are kept blinded to the allocation during the study.
Allocation
Randomized
Enrollment
389 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
Study drug. Supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet (no active treatment). The placebo tablet is matched to the study drug for taste, color, and size.
Intervention Type
Dietary Supplement
Intervention Name(s)
Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).
Intervention Description
Half of the patients are randomized to supplementation with MK-7 (720 µg/day) including the recommended daily dose of vitamin D (25 µg/day).
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Half of the patients are randomized to placebo treatment (no active treatment).
Primary Outcome Measure Information:
Title
Aortic valve calcification
Description
The primary endpoint is the change in aortic valve calcification. The natural history of the aortic valve calcification is not adequately understood, and accordingly the changes are analyzed in two prespecified patient subgroups (AVC score 300-599 and ≥600, respectively).
Time Frame
From baseline to two years of follow-up
Secondary Outcome Measure Information:
Title
Arterial calcification
Description
Change in compiled arterial calcification by non-contrast CT
Time Frame
From baseline to two years of follow-up
Title
Aortic size
Description
Change in aortic diameter
Time Frame
From baseline to two years of follow-up
Title
Coronary plaque composition
Description
Change in total plaque burden in the coronaries and carotid arteries by contrast CT
Time Frame
From baseline to two years of follow-up
Title
Aortic valve area
Description
Change in aortic valve area by transthoracic echocardiography
Time Frame
From baseline to two years of follow-up
Title
Bone mineral density
Description
Change in bone mineral density as quantitative CT of the columna lumbalis and hip region
Time Frame
From baseline to two years of follow-up
Title
Biomarkers of calcification
Description
Change in matrix-Gla proteins and osteocalcin with different phosphorylation (p and dp) and carboxylation forms (c and uc).
Time Frame
From baseline to two years of follow-up
Title
Quality of life
Description
Change in quality of life
Time Frame
From baseline to two years of follow-up

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants in the Danish Cardiovascular Screening Trial (Trials. 2015 Dec 5;16:554) with an aortic valve calcification score above 300, but without aortic valve stenosis are eligible. Exclusion Criteria: Known aortic valve disease (peak velocity ≥3.0 m/s) History of venous thrombosis or other coagulation disorders or use of vitamin K antagonists Disorders of calcium and phosphate metabolism A life-expectancy < 5 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Axel CP Diederichsen, PhD
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology, Odense University Hospital
City
Odense
State/Province
Odense C
ZIP/Postal Code
DK-5000
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
30139903
Citation
Lindholt JS, Frandsen NE, Fredgart MH, Ovrehus KA, Dahl JS, Moller JE, Folkestad L, Urbonaviciene G, Becker SW, Lambrechtsen J, Auscher S, Hosbond S, Alan DH, Rasmussen LM, Gerke O, Mickley H, Diederichsen A. Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial. BMJ Open. 2018 Aug 23;8(8):e022019. doi: 10.1136/bmjopen-2018-022019.
Results Reference
background
PubMed Identifier
35465686
Citation
Diederichsen ACP, Lindholt JS, Moller S, Ovrehus KA, Auscher S, Lambrechtsen J, Hosbond SE, Alan DH, Urbonaviciene G, Becker SW, Fredgart MH, Hasific S, Folkestad L, Gerke O, Rasmussen LM, Moller JE, Mickley H, Dahl JS. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022 May 3;145(18):1387-1397. doi: 10.1161/CIRCULATIONAHA.121.057008. Epub 2022 Apr 25.
Results Reference
derived
Links:
URL
https://bmjopen.bmj.com/content/8/8/e022019.long
Description
Protocol

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The Aortic Valve DECalcification (AVADEC) Trial

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