Edinburgh Clinical Trials

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.
 
SALTIREII logo
Chief Investigator: Professor David Newby
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:
 
Trial Unblinding Information: In circumstances where unblinding is necessary please refer to the protocol and follow instructions provided. Contact details are provided below.
 
GDPR Privacy Statement: If you have participated in this study and would like to read how it complies with GDPR, please read this document.
 
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)