Clinical Trial Results:
Elafin Myocardial Protection from Ischaemia RepErfusion injury: A randomised trial to investigate the effect of Elafin on myocardial injury and inflammation in coronary bypass surgery (EMPIRE)
Summary
|
|
EudraCT number |
2010-019527-58 |
Trial protocol |
GB |
Global end of trial date |
16 Nov 2013
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
01 Aug 2020
|
First version publication date |
01 Aug 2020
|
Other versions |
|
Summary report(s) |
Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
2010-019527-58
|
||
Additional study identifiers
|
|||
ISRCTN number |
ISRCTN82061264 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
ACCORD (University of Edinburgh & NHS Lothian)
|
||
Sponsor organisation address |
47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
|
||
Public contact |
Kat Oatey, University of Edinburgh, +44 0131 537 3841, k.oatey@ed.ac.uk
|
||
Scientific contact |
Dr Peter Henriksen, University of Edinburgh, +44 0131 537 3834, phenrik1@staffmail.ed.ac.uk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
14 Apr 2015
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
26 Sep 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
16 Nov 2013
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To demonstrate that perioperative Elafin administration reduces post-ischaemic inflammatory myocardial injury following coronary artery bypass graft surgery.
|
||
Protection of trial subjects |
This single center clinical trial was performed with the approval of the national research ethics committee (11/MRE00/5), in accordance with the Declaration of Helsinki (2000), under a Clinical Trial Authorization (27586/0015/001-0001) from the Medicine and Healthcare products Regulatory Authority (MHRA, United Kingdom), and the written informed consent of all participants.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Aug 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 87
|
||
Worldwide total number of subjects |
87
|
||
EEA total number of subjects |
87
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
47
|
||
From 65 to 84 years |
40
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
Between June 2011 and September 2013, consecutive patients referred for elective CABG surgery were recruited from two clinics at Edinburgh Heart Centre. Patients were 18 years or older, and were referred for isolated CABG surgery requiring 2 or more grafts. Exclusion criteria included patients with recent myocardial infarction (within 1 month of su | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
A total of 189 patients were screened for recruitment of whom 29 were excluded, 79 declined to participate, 88 patients gave informed consent and 1 died before surgery leaving 87 patients to undergo randomisation. | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | ||||||||||||||||||
Blinding implementation details |
Treatment was blinded to both the research team and the subject. To ensure blinding, study drugs were prepared by staff independent of the study investigators or clinical team responsible for the patients care.
|
||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
Active | ||||||||||||||||||
Arm description |
Elafin | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Elafin
|
||||||||||||||||||
Investigational medicinal product code |
CAS number: 820211-82-3.
|
||||||||||||||||||
Other name |
N/A
|
||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||
Dosage and administration details |
Intravenous recombinant human Elafin (Proteo Biotech AG, Germany) 200 mg was prepared and infused as aqueous solution of 250 mL 0.9% saline.
|
||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||
Arm description |
Placebo | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
0.9% saline
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
N/A
|
||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||
Dosage and administration details |
Saline placebo was prepared and infused as aqueous solution of 250 mL 0.9% saline.
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Elafin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Active
|
||
Reporting group description |
Elafin | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Placebo |
|
|||||||||||||
End point title |
The primary endpoint is the log area under the curve for plasma troponin I concentration profile over the first 48 h | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
48 hours
|
||||||||||||
|
|||||||||||||
Notes [1] - 2 patients AUC could not be calculated - no Troponin I blood result/ highly-sensitive Troponin value [2] - 2 patients AUC could not be calculated - no Troponin I blood result/ highly-sensitive Troponin value |
|||||||||||||
Statistical analysis title |
48 hour plasma troponin I concentration profile | ||||||||||||
Statistical analysis description |
Log area under the curve for plasma troponin I concentration profile over the first 48 h. General linear model.
|
||||||||||||
Comparison groups |
Active v Placebo
|
||||||||||||
Number of subjects included in analysis |
83
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.181 [3] | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.75 | ||||||||||||
upper limit |
0.14 | ||||||||||||
Notes [3] - P=0.05 |
|
|||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All adverse events (AEs) that occur after joining the trial must be reported in detail in the CRF. In the case of an AE, the Investigator should initiate the appropriate treatment according to their medical judgement. Participants with AEs present at the
|
||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Elafin | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No treatment received
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were consented but had received no treatment at the time of adverse event | ||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Mar 2011 |
Removing women of child bearing potential. Protocol v3 |
||
16 Jun 2011 |
Detailing the delay in supply of feraheme but adding text to protocol and PIS to allow start of recruitment without this aspect of study. Protocol v5 |
||
21 Mar 2012 |
Extension of shelf life. Protocol v7 |
||
05 Sep 2012 |
Addition of 10 healthy volunteers. Protocol v8 |
||
10 Apr 2013 |
Extension request and addition of 36 additional participants without MRI scans. Protocol v9 |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
N/A | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/26310261 |