Clinical Trial Results:
Assessment of Osteoblastic Activity With 18F-Fluoride in Aortic Bioprosthesis Structural Valve Dysfunction (SVD)
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Summary
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EudraCT number |
2016-002886-77 |
Trial protocol |
FR |
Global end of trial date |
03 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2022
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First version publication date |
29 Mar 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RC16_0137
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03015818 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CHU Nantes
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Sponsor organisation address |
5 allée de l'île Gloriette , Nantes, France, 44000
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Public contact |
Direction de la Recherche, CHU de Nantes, 0033 2 40 08 49 84, soizic.boinet@chu-nantes.fr
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Scientific contact |
Direction de la Recherche, CHU de Nantes, 0240084984 2 40 08 49 84, soizic.boinet@chu-nantes.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Oct 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 May 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To demonstrate in patients with severe aortic bioprosthesis degeneration the existence of an active calcification phenomenon in the bioprosthetic tissue by 18F-NaF PET
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Protection of trial subjects |
PET slots are dedicated to research to allow patients who agree to participate in the study to have the PET scan on the same day as the routine care visit for their bioprosthesis.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 25
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Worldwide total number of subjects |
25
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EEA total number of subjects |
25
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
16
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85 years and over |
4
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Recruitment
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Recruitment details |
25 patients were included. 4 out of 25 patients did not undergo FNA PET, so the study population is 21 patients | ||||||||||
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Pre-assignment
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Screening details |
The study population consisted of patients operated who underwent aortic valve replacement, isolated or associated with another surgical procedure with the installation of a biological valve of animal origin and with echographic signs of severe or moderate degeneration of this biological valve. | ||||||||||
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Period 1
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Period 1 title |
essais global (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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18F-NaF PET-CT | ||||||||||
Arm description |
Patients underwent 18F-NaF PET/CT (125 MBq), 18F-FDG PET/CT and thoracic CT to evaluate bioprosthesis calcified plaque burden. Radi-otracer uptake on bioprostheses was analyzed both qualitatively and quantitatively by measuring the blood-pool-corrected standardized up-take value (target-to-background ratio (TBR)). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
18F-NaF
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Radiopharmaceutical precursor
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Routes of administration |
Intravenous use
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Dosage and administration details |
18F-NaF is administered once in the study, as a single direct IV dose of 125 MBq. There is no dose adjustment.
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Baseline characteristics reporting groups
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Reporting group title |
essais global (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
analysis of the study population
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analyses of the primary and secondary endpoints are performed on an intention-to-treat basis. Data from all included patients are used for the statistical analysis
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End points reporting groups
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Reporting group title |
18F-NaF PET-CT
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Reporting group description |
Patients underwent 18F-NaF PET/CT (125 MBq), 18F-FDG PET/CT and thoracic CT to evaluate bioprosthesis calcified plaque burden. Radi-otracer uptake on bioprostheses was analyzed both qualitatively and quantitatively by measuring the blood-pool-corrected standardized up-take value (target-to-background ratio (TBR)). | ||
Subject analysis set title |
analysis of the study population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The analyses of the primary and secondary endpoints are performed on an intention-to-treat basis. Data from all included patients are used for the statistical analysis
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End point title |
Evaluation of the 18F-NaF binding rate on the valve bioprosthesis | |||||||||
End point description |
The intensity of 18F-NaF binding to the valve bioprosthesis is assessed by the tissue to blood pool ratio (TBR).
Patients are separated into two groups according to echocardiographic data moderate degeneration (functional area ≥ 0.8 and ≤ 1.2 cm²) or severe degeneration (functional area < 0.8 cm²) and the 18F-NaF TBR will be compared between compared between the two groups.
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End point type |
Primary
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End point timeframe |
The day of the 18F-NaF PET scan
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| Notes [1] - The population studied for FNA PET is 21 patients (4 of 25 patients did not perform FNA PET) |
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Statistical analysis title |
Comparison of ultrasound characteristics | |||||||||
Statistical analysis description |
All statistical analyses will be descriptive. Patients will be separated into two groups according to their functional surface measured on ultrasound: moderate degeneration (functional surface ≥ 0.8 and ≤ 1.2 cm²) or severe degeneration (functional surface < 0.8 cm²). This obtained variable is analysed as a binary qualitative criterion. The ratio of valve uptake to blood background (TBR) of 18F-NaF is analysed as a quantitative variable. A Mann-Whitney test will be used to compare the 2 groups.
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Comparison groups |
18F-NaF PET-CT v analysis of the study population
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
P-value |
= 5 | |||||||||
Method |
Mann- Whitney | |||||||||
Confidence interval |
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| Notes [2] - descriptive |
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End point title |
association of an inflammatory process by 18F-FDG PET in severe forms of SVD | |||||||||
End point description |
comparison of 18F-FDG RBT between the two groups defined in the primary endpoint
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End point type |
Secondary
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End point timeframe |
6 months
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Statistical analysis title |
comparison of TBRs | |||||||||
Statistical analysis description |
A comparison of 18F-NaF and 18F-FDG TBRs respectively is performed between leaky and stenosing forms of SVD. stenosing forms of SVD
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Comparison groups |
18F-NaF PET-CT v analysis of the study population
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 5 | |||||||||
Method |
Mann- Whitney | |||||||||
Confidence interval |
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End point title |
Respective correlations between the valvular TBR of 18F-NaF and 18F-FDG and ultrasound parameters | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
M6
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Statistical analysis title |
calculation of respective correlations | |||||||||
Statistical analysis description |
Calculation of the respective correlations between the 18F-NaF and 18F-FDG valve TBR and the following ultrasound parameters: aortic leak grade, maximum trans-prosthetic velocity, mean trans-prosthetic pressure gradient, indexed and non-indexed body surface area of the valve, visual ultrasound scores of degeneration, thickening, restriction and calcification of the valve leaflets.
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Comparison groups |
18F-NaF PET-CT v analysis of the study population
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||
P-value |
= 5 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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| Notes [3] - descriptive |
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Adverse events information
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Timeframe for reporting adverse events |
From D0 to M6
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Assessment type |
Systematic | ||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||
Dictionary version |
21
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Reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | ||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Feb 2018 |
Extension of the inclusion period by 6 months |
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07 Nov 2018 |
The MS2 amendment concerns: an extension of the inclusion period by one year and an increase in the number of subjects to 40 patients in total.
The patient information letter and consent form have been modified to comply with the General Data Protection Regulation |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
