SALTIRE II
Bisphosphonates and RANKL inhibition in Aortic Stenosis
Calcific aortic stenosis is the commonest form of valve disease in the western world. It has become a major health care burden and, left untreated, is fatal. Currently ‘watchful waiting’ represents the mainstay of its management with eventual aortic valve replacement triggered by the onset of symptoms. The development of an effective medical therapy has proved elusive and is a major unmet clinical need. We have demonstrated that calcification rather than inflammation is the major driver of aortic valve disease progression, and is a potential target for novel therapeutic intervention.
Bisphosphonates and the Receptor Activator of Nuclear factor Kappa B Ligand (RANKL) inhibitor, denosumab, have anti-osteoporotic actions through modification of calcium homeostasis and mineralisation. These agents have the potential to reduce calcification and mineralisation of aortic valve tissue and thereby reduce or halt disease progression.
We propose a double blind randomised controlled trial to establish whether alendronate or denosumab will retard or halt disease progression in patients with aortic stenosis. Outcome measures will include aortic valve calcium score by computed tomography, aortic-jet velocity determined by Doppler echocardiography, and aortic valve calcification activity by 18F-fluoride positron emission tomography. The primary end-point will be the change in aortic valve calcium score at two years. The identification of an effective medical therapy would prove a major advance in the management of patients with aortic stenosis.
Number and location of participating sites (by region/ country): UK Single Centre at Edinburgh Royal Infirmary
EudraCT number: 2014-001112-19
The Clinical Trials gov number is NC02132026
Funder: British Heart Foundation
Start and End date of grant award December 2014 to November 2019
Current Status: complete awaiting publication
Link to Publication:
- Pawade TA, Cartlidge TR, Jenkins WS, Adamson PD, Robson P, Lucatelli C, Van Beek EJ, Prendergast B, Denison AR, Forsyth L, Rudd JH, Fayad ZA, Fletcher A, Tuck S, Newby DE, Dweck MR. Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2016 Oct;9(10). pii: e005131
Trial Unblinding Information: In circumstances where unblinding is necessary please refer to the protocol and follow instructions provided. Contact details are provided below.
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Contact details: Sponsor: ACCORD
Chief Investigator: Professor David Newby, Centre of Cardiovascular Science, Chancellor’s Building, 51 Little France Crescent, Edinburgh EH16 4SB.
Principal Investigator: Rong Bing
Trial Manager: Dr Laura Forsyth
ECTU Involvement: Trial management, Statistics, Database and randomisation service
(UKCRC)