Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis. (SALTIRE II)
|ClinicalTrials.gov Identifier: NCT02132026|
Recruitment Status : Completed
First Posted : May 6, 2014
Last Update Posted : March 26, 2020
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] ).
The data from this study will then be used to design a larger trial.
|Condition or disease||Intervention/treatment||Phase|
|Calcific Aortic Stenosis||Drug: Denosumab Drug: Alendronic Acid Drug: Denosumab Placebo Drug: Alendronic Acid Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||152 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||SALTIRE II: Bisphosphonates and RANKL Inhibition in Aortic Stenosis|
|Actual Study Start Date :||November 12, 2014|
|Actual Primary Completion Date :||November 28, 2019|
|Actual Study Completion Date :||November 28, 2019|
Active Comparator: Alendronic Acid
50 patients will receive once weekly Alendronic Acid tablets (70mg).
Drug: Alendronic Acid
Placebo Comparator: Alendronic Acid placebo
25 patients will receive alendronic acid placebo tablets.
Drug: Alendronic Acid Placebo
Inert Capsule containing lactose monohydrate manufactured and labelled by Investigational Supplies Group (ISG) University of Edinburgh.
Active Comparator: Denosumab
50 patients will receive 6 monthly denosumab injections
Placebo Comparator: Denosumab Placebo
25 patients will receive a 6 monthly placebo injection.
Drug: Denosumab Placebo
subcutaneous injection of 0.9%Saline at baseline, 6 months, 12 months and 18 months
- Change in aortic valve calcium score [ Time Frame: Measured at Baseline, 6 months and 2 years ]The change in calcium score will be assessed using computed tomography and is an assessment of disease severity.
- Change in aortic valve 18F-NaF uptake [ Time Frame: Measured at baseline and 6 months ]This is determined by positron emission tomography and is a measure of calcification activity.
- Change in aortic-jet velocity [ Time Frame: Measured at baseline, 6, 12, 18 and 24 months ]This will be determined by Doppler echocardiography and is a measure of disease severity.
- Change in thoracic aortic and coronary artery calcium score [ Time Frame: Measured at baseline and 2 years ]This will be determined by computed tomography and is an additional assessment of vascular calcification.
- Change in thoracic spine bone mineral density [ Time Frame: Measured at baseline and 2 years ]This will be determined by quantitative computed tomography.
- Change in quality of life determined by Short Form 36 Questionnaire [ Time Frame: Measured at baseline and 2 years ]Questionnaire
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02132026
|Clinical Research Facility University of Edinburgh|
|Edinburgh, United Kingdom, EH16 4SA|
|Principal Investigator:||Rong Bing, MbChB||University of Edinburgh and NHS Lothian|
|Study Chair:||David E Newby, BA BSc PhD BM DM FRCP DSc FRSE||University of Edinburgh and NHS Lothian|