Testing if vitamin K1 reduces the progression of non-severe calcific aortic stenosis: design and rationale of the Prevention of Aortic Stenosis Progression Phylloquinone Ossification Reduction Trial (PASSPORT).

Aims: Calcific aortic stenosis (CAS) is the most common heart valvulopathy in high-income countries. There is no known treatment for CAS other than replacement of the valve in severe, symptomatic disease. Observational studies and a small openlabel randomized trial have reported that vitamin K1 supplementation may reduce the progression rate of calcification and obstruction in CAS. Methods and results: 3PASSPORT(ACTRN12622000447752) will be a prospective, randomized, double-blind, placebo-controlled clinical trial investigating if nutritional supplementation with 10 mg of vitamin K1 can reduce the rate of valvular calcification and haemodynamic progression in CAS. Patients identified to have mild or moderate CAS based on standard echocardiographic criteria will be randomized 1:1 to vitamin K1 10 mg per day or matched placebo, and followed-up for a mean period of 16 months, ranging from 12 to 21 months. The primary endpoint will be the difference in aortic valve calcification volume, measured by computed tomography aortic valve calcium score, from baseline to follow-up, and secondary endpoints will include the change in echocardiographic progression of CAS, including peak flow velocity, mean pressure gradient, and aortic valve area. The trial is registered with the Australian New Zealand. Clinical Trials Registry (ACTRN12622000447752). The trial has met its recruitment target of 108 participants. Conclusion: PASSPORT will be prospective, randomized, double-blind clinical trial powered to demonstrate if oral supplementation with vitamin K1 reduces the progression of valvular calcification and echocardiographic severity of disease in patients with non-severe CAS. The trial results will have implications for the management of CAS, for which there is currently no medical treatment.