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18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome (18F-FAABULOUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02304276
Recruitment Status : Active, not recruiting
First Posted : December 1, 2014
Last Update Posted : June 21, 2021
Sponsor:
Collaborators:
NHS Lothian
Cambridge University Hospitals NHS Foundation Trust
Papworth Hospital NHS Foundation Trust
Bichat Hospital
Information provided by (Responsible Party):
University of Edinburgh

Brief 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). 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.

Condition or disease Intervention/treatment Phase
Heart; Complications, Valve, Prosthesis Radiation: 18F-Fluoride PET-CT Radiation: CT calcium score of aortic valve Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: 18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome
Actual Study Start Date : January 2015
Actual Primary Completion Date : September 2018
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Calcium

Arm Intervention/treatment
Active Comparator: 1 (Explanted valves)

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
Radiation: 18F-Fluoride PET-CT
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

Experimental: 2 (AVR)

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)
Radiation: 18F-Fluoride PET-CT
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

Radiation: CT calcium score of aortic valve
CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)

Experimental: 3 (TAVI)

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)
Radiation: 18F-Fluoride PET-CT
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

Radiation: CT calcium score of aortic valve
CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. CT calcium score of aortic valve [ Time Frame: Baseline and 2 years ]
    Change in aortic valve calcium score (Agatston units) from baseline to 2 years as determined by CT

  2. Echocardiographic evaluation of aortic valve function [ Time Frame: Baseline, 1 year and 2 years ]
    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

  3. Frequency of major adverse cardiovascular events [ Time Frame: 5 years ]
    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

  4. Immunohistochemical staining of explanted aortic bioprostheses for marker of calcification [ Time Frame: intraoperative ]
    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.



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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
  • 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.

Exclusion Criteria:

  • Inability to give informed consent
  • Pregnancy
  • Breastfeeding
  • Claustrophobia
  • Allergy to iodinated contrast
  • Liver failure
  • Chronic kidney disease (with estimated glomerular filtration rate <30 mL/min)
  • Metastatic malignancy
  • Paget's disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304276


Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Cambridge University Hospitals NHS Foundation Trust
Papworth Hospital NHS Foundation Trust
Bichat Hospital
Investigators
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Principal Investigator: Marc Dweck, MBChB PhD University of Edinburgh, Scotland
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02304276    
Other Study ID Numbers: 147780
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: June 21, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Calcium
Fluorides
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Cariostatic Agents
Protective Agents