Clinical Trial Results:
Prediction of Recurrent Events with 18F-Fluoride to Identify Ruptured and High-risk Coronary Artery Plaques in Patients with Myocardial Infarction - the PREFFIR study
Summary
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EudraCT number |
2014-004021-41 |
Trial protocol |
GB |
Global end of trial date |
20 May 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Dec 2023
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First version publication date |
09 Dec 2023
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Other versions |
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 |
15-SS-0059
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02278211 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Edinburgh &NHs Lothian
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Sponsor organisation address |
Old College, South Bridge, Edinburgh, United Kingdom, EH8 9YL
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Public contact |
Professor David Newby, University of Edinburgh, +44 0131 242 6515 , d.e.newby@ed.ac.uk
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Scientific contact |
Professor David Newby, University of Edinburgh, +44 0131 242 6515 , d.e.newby@ed.ac.uk
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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 |
20 May 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 May 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
20 May 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine whether coronary 18F-fluoride uptake is associated with major adverse cardiac events in patients with multi-vessel coronary artery disease and recent myocardial infarction.
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Protection of trial subjects |
The study was overseen by the Edinburgh Clinical Trials Unit and an independent trial steering committee. The study was performed under a clinical trial authorization from the Medicines and Healthcare products Regulatory Agency, with approval from the South East Scotland Research Ethics Committee in accordance with the Declaration of Helsinki24 and
with the written informed consent of each participant.
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Background therapy |
The study population consisted of patients aged 50 years or older with a recent (within 21 days) type 1 MI and multivessel coronary artery disease shown on invasive coronary angiography, defined as at least 2 major epicardial vessels with either more than 50% luminal stenosis or previous coronary revascularization(percutaneous coronary intervention or coronary artery bypass graft surgery). | ||
Evidence for comparator |
No Comparator | ||
Actual start date of recruitment |
28 Sep 2015
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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 |
United Kingdom: 694
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Country: Number of subjects enrolled |
United States: 5
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Country: Number of subjects enrolled |
Australia: 5
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Worldwide total number of subjects |
704
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EEA total number of subjects |
0
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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) |
393
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From 65 to 84 years |
305
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85 years and over |
6
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Recruitment
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Recruitment details |
This was an international, multicenter, prospective longitudinal cohort study conducted in 9 centres across 4 countries between September 2015 and February 2020. | ||||||
Pre-assignment
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Screening details |
Among 2684 patients screened, 995 were eligible, a total of 712 participants were recruited and attended for baseline 18Fsodium fluoride PET and CT scans. Of these, 6 participants received the radiotracer but were unable to complete the scan, and 2 patients were scanned but image reconstruction could not be completed. The study population was 704. | ||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Overall Trial | ||||||
Arm description |
This was a cohort study, not a randomised trial. | ||||||
Arm type |
Overall Trial | ||||||
Investigational medicinal product name |
[18F] Sodium Fluoride
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Investigational medicinal product code |
18FNaF
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
250 MBq
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
Analysis Population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Analysis Population Overall
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All Patients analysed
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Subject analysis set title |
Low coronary atherosclerotic plaque activity
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Low coronary atherosclerotic plaque activity was defined as coronary microcalcification activity [CMA] of 0.
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Subject analysis set title |
High coronary atherosclerotic plaque activity
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
High coronary atherosclerotic plaque activity was defined as a coronary microcalcification activity (CMA) greater than 0.
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End points reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
This was a cohort study, not a randomised trial. | ||
Subject analysis set title |
Analysis Population Overall
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All Patients analysed
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Subject analysis set title |
Low coronary atherosclerotic plaque activity
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Low coronary atherosclerotic plaque activity was defined as coronary microcalcification activity [CMA] of 0.
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Subject analysis set title |
High coronary atherosclerotic plaque activity
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
High coronary atherosclerotic plaque activity was defined as a coronary microcalcification activity (CMA) greater than 0.
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End point title |
Primary Endpoint | ||||||||||||||||
End point description |
Primary outcome of cardiac death, non-fatal recurrent myocardial infarction, or unscheduled (late) coronary revascularisation for patients in analysis population
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End point type |
Primary
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End point timeframe |
Participants were followed up by site investigators until the last recruited patient had completed their 2-year follow-up visit.
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Statistical analysis title |
Hazard ratio for primary outcome | ||||||||||||||||
Statistical analysis description |
Time to event analysis, Cox regression.
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Comparison groups |
Low coronary atherosclerotic plaque activity v High coronary atherosclerotic plaque activity
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Number of subjects included in analysis |
704
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.2 | ||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||
Point estimate |
1.25
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.89 | ||||||||||||||||
upper limit |
1.76 |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events within 48 hours of baseline visit
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Adverse event reporting additional description |
Performance of PET and coronary CT angiography was associated with 15 adverse events, which were predominantly
iodinated contrast reactions. Two events were graded as serious: palpitation and β-blocker–induced bradycardia
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||
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 Trial
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Reporting group description |
Site Investigator Reported Adverse Events. The total number of subjects exposed to IMP is 712. The denominator is 712, not 704. Eight subjects had IMP but didn't progress into the study. | ||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||
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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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03 May 2019 |
IB updated to include a stand-alone RSI section |
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14 Apr 2020 |
Update to the primary and secondary endpoints.
Removal of PREFFIR-TIME 6 week timepoint from protocol.
Protocol window on 1 yr and subsequent annual reviews amended from -/+2weeks to -2/+26 weeks.
Protocol window on 2 year visits amended from -/+2 weeks to 0 to +52 weeks.
Protocol wording updated to allow 2 year CTCA scan to be performed on a separate date from other 2 year assessments if it is not possible for the scan to be performed on the same date.
Data protection wording updated to reflect sponsor's approved wording.
Typographical errors corrected throughout protocol.
Data management section added to the protocol to reflect the Sponsor's current protocol template. |
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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. | |||
There was a lower event rate in the study population despite recruiting patients with MI and multivessel disease. There was a low inclusion of women . We did not undertake end point adjudication because there was strict blinding of study imaging. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/37379010 |