Heart; Complications, Valve, Prosthesis18F-FAABULOUSNCT02304276
18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome
A study testing 18F-Fluoride PET-CT and CT calcium score of aortic valve in people with Heart; Complications, Valve, Prosthesis, run by University of Edinburgh.
Trial summary
This study will evaluate the two main types of replacement tissue heart valve used in current practice, comparing outcomes from surgical aortic valve replacement (AVR) with that of the more recently introduced "key-hole" procedure called transcatheter aortic valve implantation (TAVI). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Heart; Complications, Valve, Prosthesis
- What is being tested?
- 18F-Fluoride PET-CT and CT calcium score of aortic valve
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- No sites listed yet
- Study dates
- Jan 2015to 30 Oct 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cohort 1
- able to provide informed consent
- aged over 40 years
- patients with a bioprosthetic aortic valve who are due to undergo a redo-surgical aortic valve replacement
- Cohort 2
- able to provide informed consent
Show all 12Show fewer
- aged over 40 years
- patients at 1 month (n=10), 2 years (n=20), 5 years (n=20) and 10 years (n=20) following surgical bioprosthetic aortic valve replacement
- Cohort 3
- able to provide informed consent
- aged over 40 years
- patients at 1 month (n=10), 2 years (n=20) and 5 years (n=20) following transcatheter aortic valve implantation (TAVI) with the Edward's SAPIEN and the COREVALVE.
Who cannot join
- Inability to give informed consent
- Pregnancy
- Breastfeeding
- Claustrophobia
- Allergy to iodinated contrast
- Liver failure
Show all 9Show fewer
- Chronic kidney disease (with estimated glomerular filtration rate <30 mL/min)
- Metastatic malignancy
- Paget's disease
About this study
This study will evaluate the two main types of replacement tissue heart valve used in current practice, comparing outcomes from surgical aortic valve replacement (AVR) with that of the more recently introduced "key-hole" procedure called transcatheter aortic valve implantation (TAVI). Participants will be recruited at various time points ranging from 1 month to 10 years following valve replacement with either AVR or TAVI. It is thought that progressive calcium (chalk) formation is responsible for the failure of the majority of these valves. All participants will therefore have a PET-CT scan with a special type of "tracer" called 18F-fluoride in order to measure active calcium formation in the valve. They will then have annual clinical follow-up for 5 years and be invited back for a repeat CT scan at 2 years to measure change in calcium burden. This study aims to investigate, firstly, the effects of valve age and type on calcium formation as measured by PET-CT and, secondly, whether this measure of calcium formation can help to predict how long different types of valve will last. If successful, 18F-fluoride PET-CT could become a valuable tool for testing new treatments to improve valve longevity and new valve designs.
Read the detailed description
Aortic stenosis is the commonest form of valve disease in the western world and the leading indication for valve surgery. Bioprosthetic valves are known to degenerate via a process that is predominantly driven by calcification. Transcatheter aortic valve implantation (TAVI) has recently emerged as a less invasive alternative to conventional aortic valve replacement (AVR) surgery. Whilst this technique holds great promise, long-term follow up data are lacking and the longevity of these valves remains to be established.
In this longitudinal, cross-sectional study of 180 subjects with either surgical or transcatheter implanted bioprostheses, this study proposes to look for the earliest signs of active calcification using 18F-fluoride positron emission tomography (PET). During a 5 year follow-up period, this study hopes to demonstrate that 18F-fluoride PET will predict subsequent bioprosthetic valve degeneration and identify patients at risk of premature valve failure. The study also hopes that it will inform about the comparative durability of novel percutaneous valves. If successful, 18F-Fluoride could provide a useful method of assessing novel therapeutic strategies targeted at improving the longevity of bioprostheses and help to guide future valve design.
- Conditions
- Heart; Complications, Valve, Prosthesis
- Being tested
- 18F-Fluoride PET-CT, CT calcium score of aortic valve
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18F-Fluoride PET-CTRadiation
Injection of 18F-Fluoride with target activity 125MBq giving an anticipated radiation exposure of 3mSv CT scanning protocol giving an anticipated radiation exposure of 13mSv
CT calcium score of aortic valveRadiation
CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)
| Study group | Role | What they receive |
|---|---|---|
| 1 (Explanted valves) | Active comparator | 10 subjects who are due to undergo repeat aortic valve replacement surgery
Investigations:
1. Baseline 18F-Fluoride PET-CT scan
2. Retrieval of explanted bioprosthetic aortic valve at time of surgery for analysis Receives: Radiation: 18F-Fluoride PET-CT |
| 2 (AVR) | Experimental | 70 subjects with surgical bioprosthetic AVR, to include 10 subjects who have had a valve replacement < 1 month; 20 at 2 years; 20 at 5 years and 20 at >10 years.
Investigations:
1. Baseline 18F-Fluoride PET-CT scan
2. Repeat CT calcium score of aortic valve at 2 years
3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram) Receives: Radiation: 18F-Fluoride PET-CT; Radiation: CT calcium score of aortic valve |
| 3 (TAVI) | Experimental | 50 subjects who have undergone TAVI with the COREVALVE and 50 subjects with the SAPIEN valve. In each group this will include 10 subjects who have had TAVI < 1 month; 20 at 2 years and 20 at 5 years.
Investigations:
1. Baseline 18F-Fluoride PET-CT scan
2. Repeat CT calcium score of aortic valve at 2 years
3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram) Receives: Radiation: 18F-Fluoride PET-CT; Radiation: CT calcium score of aortic valve |
What is being measured
The primary outcome is the main question the study is designed to answer.
18F-Fluoride uptake in aortic bioprostheses
18F-Fluoride uptake expressed as tissue to background ratio (TBR) in aortic valve bioprostheses of different age and type as measured by PET/CT
Measured: Baseline
Secondary outcomes (4)
CT calcium score of aortic valve
Change in aortic valve calcium score (Agatston units) from baseline to 2 years as determined by CT
Measured: Baseline and 2 years
Echocardiographic evaluation of aortic valve function
Change in echocardiographic parameters of aortic valve function (both stenosis and regurgitation) from baseline to 1 year and 2 years as determined by Doppler echocardiography
Measured: Baseline, 1 year and 2 years
Frequency of major adverse cardiovascular events
Frequency of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, admission with heart failure, repeat valve surgery) as determined by annual clinical follow-up of study population over 5 years
Measured: 5 years
Immunohistochemical staining of explanted aortic bioprostheses for marker of calcification
Immunohistochemical staining for markers of mineralisation (alkaline phosphatase, Runx-2, osteocalcin) in explanted aortic valve bioprostheses expressed as a percentage of total valve surface area.
Measured: intraoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionSep 2018
- Study completion30 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart; Complications, Valve, ProsthesisStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, Cambridge University Hospitals NHS Foundation Trust, Papworth Hospital NHS Foundation Trust, Bichat Hospital
- Responsible party
- Sponsor
- Investigators
- Marc Dweck, MBChB PhD, Principal investigator, University of Edinburgh, Scotland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02304276
- Sponsor's protocol ID
- 147780
- Acronym
- 18F-FAABULOUS
- Status last verified
- May 2024
- First submitted
- 10 Nov 2014
- Last updated
- 21 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cartlidge TRG, Doris MK, Sellers SL, Pawade TA, White AC, Pessotto R, Kwiecinski J, Fletcher A, Alcaide C, Lucatelli C, Densem C, Rudd JHF, van Beek EJR, Tavares A, Virmani R, Berman D, Leipsic JA, Newby DE, Dweck MR. Detection and Prediction of Bioprosthetic Aortic Valve Degeneration. J Am Coll Cardiol. 2019 Mar 19;73(10):1107-1119. doi: 10.1016/j.jacc.2018.12.056.
PubMed 30871693Kwiecinski J, Tzolos E, Cartlidge TRG, Fletcher A, Doris MK, Bing R, Tarkin JM, Seidman MA, Gulsin GS, Cruden NL, Barton AK, Uren NG, Williams MC, van Beek EJR, Leipsic J, Dey D, Makkar RR, Slomka PJ, Rudd JHF, Newby DE, Sellers SL, Berman DS, Dweck MR. Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation. Circulation. 2021 Oct 26;144(17):1396-1408. doi: 10.1161/CIRCULATIONAHA.121.056891. Epub 2021 Aug 29.
PubMed 34455857
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome
- ClinicalTrials.gov ID
- NCT02304276
- Acronym / sponsor ID
- 18F-FAABULOUS / 147780
- Conditions
- Heart; Complications, Valve, Prosthesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, Cambridge University Hospitals NHS Foundation Trust, Papworth Hospital NHS Foundation Trust, Bichat Hospital
- Study start
- Jan 2015 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- 30 Oct 2020 (actual)
- First posted
- 1 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the two main types of replacement tissue heart valve used in current practice, comparing outcomes from surgical aortic valve replacement (AVR) with that of the more recently introduced "key-hole" procedure called transcatheter aortic valve implantation (TAVI). Participants will be recruited at various time points ranging from 1 month to 10 years following valve replacement with either AVR or TAVI. It is thought that progressive calcium (chalk) formation is responsible for the failure of the majority of these valves. All participants will therefore have a PET-CT scan with a special type of "tracer" called 18F-fluoride in order to measure active calcium formation in the valve. They will then have annual clinical follow-up for 5 years and be invited back for a repeat CT scan at 2 years to measure change in calcium burden. This study aims to investigate, firstly, the effects of valve age and type on calcium formation as measured by PET-CT and, secondly, whether this measure of calcium formation can help to predict how long different types of valve will last. If successful, 18F-fluoride PET-CT could become a valuable tool for testing new treatments to improve valve longevity and new valve designs.
Detailed description
Aortic stenosis is the commonest form of valve disease in the western world and the leading indication for valve surgery. Bioprosthetic valves are known to degenerate via a process that is predominantly driven by calcification. Transcatheter aortic valve implantation (TAVI) has recently emerged as a less invasive alternative to conventional aortic valve replacement (AVR) surgery. Whilst this technique holds great promise, long-term follow up data are lacking and the longevity of these valves remains to be established.
In this longitudinal, cross-sectional study of 180 subjects with either surgical or transcatheter implanted bioprostheses, this study proposes to look for the earliest signs of active calcification using 18F-fluoride positron emission tomography (PET). During a 5 year follow-up period, this study hopes to demonstrate that 18F-fluoride PET will predict subsequent bioprosthetic valve degeneration and identify patients at risk of premature valve failure. The study also hopes that it will inform about the comparative durability of novel percutaneous valves. If successful, 18F-Fluoride could provide a useful method of assessing novel therapeutic strategies targeted at improving the longevity of bioprostheses and help to guide future valve design.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 (Explanted valves) | Active comparator | Radiation: 18F-Fluoride PET-CT10 subjects who are due to undergo repeat aortic valve replacement surgery Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Retrieval of explanted bioprosthetic aortic valve at time of surgery for analysis |
| 2 (AVR) | Experimental | Radiation: 18F-Fluoride PET-CT, Radiation: CT calcium score of aortic valve70 subjects with surgical bioprosthetic AVR, to include 10 subjects who have had a valve replacement < 1 month; 20 at 2 years; 20 at 5 years and 20 at >10 years. Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Repeat CT calcium score of aortic valve at 2 years 3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram) |
| 3 (TAVI) | Experimental | Radiation: 18F-Fluoride PET-CT, Radiation: CT calcium score of aortic valve50 subjects who have undergone TAVI with the COREVALVE and 50 subjects with the SAPIEN valve. In each group this will include 10 subjects who have had TAVI < 1 month; 20 at 2 years and 20 at 5 years. Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Repeat CT calcium score of aortic valve at 2 years 3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram) |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Cohort 1
- able to provide informed consent
- aged over 40 years
- patients with a bioprosthetic aortic valve who are due to undergo a redo-surgical aortic valve replacement
- Cohort 2
Key exclusion criteria (9 listed)
- Inability to give informed consent
- Pregnancy
- Breastfeeding
- Claustrophobia
- Allergy to iodinated contrast
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 18F-Fluoride PET-CTInjection of 18F-Fluoride with target activity 125MBq giving an anticipated radiation exposure of 3mSv CT scanning protocol giving an anticipated radiation exposure of 13mSv | Radiation | 1 (Explanted valves), 2 (AVR), 3 (TAVI) |
| CT calcium score of aortic valveCT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only) | Radiation | 2 (AVR), 3 (TAVI) |
Primary outcome
18F-Fluoride uptake in aortic bioprostheses
Time frame: Baseline
18F-Fluoride uptake expressed as tissue to background ratio (TBR) in aortic valve bioprostheses of different age and type as measured by PET/CT
4 secondary outcomes
CT calcium score of aortic valve
Time frame: Baseline and 2 years
Echocardiographic evaluation of aortic valve function
Time frame: Baseline, 1 year and 2 years
Frequency of major adverse cardiovascular events
Time frame: 5 years
Immunohistochemical staining of explanted aortic bioprostheses for marker of calcification
Time frame: intraoperative
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
- Results publication: PubMed 30871693Cartlidge TRG, Doris MK, Sellers SL, Pawade TA, White AC, Pessotto R, Kwiecinski J, Fletcher A, Alcaide C, Lucatelli C, Densem C, Rudd JHF, van Beek EJR, Tavares A, Virmani R, Berman D, Leipsic JA, Newby DE, Dweck MR. Detection and Prediction of Bioprosthetic Aortic Valve Degeneration. J Am Coll Cardiol. 2019 Mar 19;73(10):1107-1119. doi: 10.1016/j.jacc.2018.12.056.
- Derived from this study: PubMed 34455857Kwiecinski J, Tzolos E, Cartlidge TRG, Fletcher A, Doris MK, Bing R, Tarkin JM, Seidman MA, Gulsin GS, Cruden NL, Barton AK, Uren NG, Williams MC, van Beek EJR, Leipsic J, Dey D, Makkar RR, Slomka PJ, Rudd JHF, Newby DE, Sellers SL, Berman DS, Dweck MR. Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation. Circulation. 2021 Oct 26;144(17):1396-1408. doi: 10.1161/CIRCULATIONAHA.121.056891. Epub 2021 Aug 29.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Dweck, MBChB PhD principal investigator
University of Edinburgh, Scotland
Questions about this trial
What is this clinical trial studying?
A study testing 18F-Fluoride PET-CT and CT calcium score of aortic valve in people with Heart; Complications, Valve, Prosthesis, run by University of Edinburgh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
18F-Fluoride uptake in aortic bioprostheses (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02304276, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024; AzTrials last refreshed its copy on 7 Nov 2026.