The Aortic Valve DECalcification (AVADEC) Trial

NCT03243890 | Completed DMC

• 1 other identifier: AVADEC
• Study Type: interventional
• Target: 389
• Locations: 1 country
• Sites: 1

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.

Conditions

Aortic Valve Stenosis; Multidetector Computed Tomography; Vitamin K 2; Randomised Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 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).

  From baseline to two years of follow-up

Secondary Outcomes (7)

• Arterial calcification

  From baseline to two years of follow-up

• Aortic size

  From baseline to two years of follow-up

• Coronary plaque composition

  From baseline to two years of follow-up

• Aortic valve area

  From baseline to two years of follow-up

• Bone mineral density

  From baseline to two years of follow-up

Study Arms (2)

Intervention

EXPERIMENTAL

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

Dietary Supplement: Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day).

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day). DIETARY_SUPPLEMENT

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

Placebo DIETARY_SUPPLEMENT

Half of the patients are randomized to placebo treatment (no active treatment).

Placebo

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Axel Diederichsen: lead

Study Sites (1)

Department of Cardiology, Odense University Hospital

Odense, Odense C, DK-5000, Denmark

Location

Related Publications (2)

• 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.

  PMID: 30139903 BACKGROUND

• 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.

  PMID: 35465686 DERIVED

Related Links

• Protocol

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

menaquinone 7

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Axel CP Diederichsen, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associated professor

Model Details: 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.

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 9, 2017
• Study Start: January 12, 2018
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: September 29, 2022

Record last verified: 2022-09

Locations

DK (1)