18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome

NCT ID: NCT02304276

Last Updated: 2024-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2020-10-30

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

18F-Fluoride PET-CT

Intervention Type: RADIATION

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

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)

Group Type: EXPERIMENTAL

18F-Fluoride PET-CT

Intervention Type: RADIATION

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 valve

Intervention Type: RADIATION

CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)

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)

Group Type: EXPERIMENTAL

18F-Fluoride PET-CT

Intervention Type: RADIATION

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 valve

Intervention Type: RADIATION

CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)

Interventions

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

Intervention Type: RADIATION

CT calcium score of aortic valve

CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)

Intervention Type: RADIATION

Eligibility 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Papworth Hospital NHS Foundation Trust

OTHER_GOV

Sponsor Role: collaborator

Bichat Hospital

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Dweck, MBChB PhD

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh, Scotland

References

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.

Reference Type: RESULT

PMID: 30871693 (View on PubMed)

Kwiecinski 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.

Reference Type: DERIVED

PMID: 34455857 (View on PubMed)

Other Identifiers

147780

Identifier Type: -

Identifier Source: org_study_id