SALTIRE 2 TRIAL

SALTIRE 2 TRIAL

clinicaltrials.gov NCT02132026

Aortic stenosis is a condition whereby one of the heart valves (aortic valve) becomes narrowed, due to calcium deposition, over time. This can lead to chest pain, heart failure and sudden death. It is the commonest valve disease requiring surgery in the developed world and as the population becomes increasingly older, it is predicted that the prevalence of aortic stenosis will double in the next 20 years. Currently the only treatment is replacement of the aortic valve. Whilst this is excellent treatment, not everyone is suitable for it.

The primary objective of our study is to determine whether 2 drugs used in the treatment of osteoporosis (a condition of bone thinning) can halt/retard the progression of aortic stenosis. This is on the basis that studies have suggested that altered regulation of calcium metabolism may be an important mechanism perpetuating the disease. Both drugs work by reducing calcium release into the bloodstream from bones and therefore calcification of the aortic valve.

150 patients will therefore be randomly allocated to either of the trial drugs which are denosumab,the bisphosphonate (alendronic acid), or a placebo.

Positron Emission Tomography (PET) scanning is a technique where biochemically active molecules are injected and are taken up at sites of ongoing calcification activity where they emit radiation and can be detected by the PET scanner. We have previously shown that this technique can demonstrate areas of newly developing calcification on an aortic valve.

We therefore propose that patients receiving bisphosphonates or denosumab will have reduced evidence of active calcification and slower progression of their disease at two years as assessed by Echocardiography (ultrasound) and a change in their calcium score (quantity of calcium on the aortic valve measured using Computed Tomography [CT] ). If successful this will be the first time we have had a drug capable of slowing disease progression in this common condition.

Research Methods and Objectives:

Single centre quadruple blinded randomised placebo controlled trial. Patients with mild and moderate aortic stenosis will be recruited. Patients will undergo baseline echocardiography, computed tomography and 18F-fluoride positron emission tomography. They will then be randomised to receive alendronate, denosumab or placebo for 2 years. Patients will undergo repeat 18F-fluoride PET at 6 months to assess if disease activity is reduced by the drugs. They will also undergo repeat echocardiography and CT calcium scoring at 2 years to assess if the drugs slow disease progression. The Primary end point of the trial is change in CT calcium score of the aortic valve at 2 years.

Principal Investigator, Co-Investigators, Other researchers:

PI Marc Dweck

Co-investigators David Newby, Dr Mhairi Doris, Dr Tania Pawade.

We work with the Edinburgh Clinical Trials Unit and are supported by project grants and research fellowships from the British Heart Foundation. For further information email marc.dweck@ed.ac.uk.