Clinical Trial Results:
Does Cyclosporine ImpRove Clinical oUtcome in ST elevation myocardial infarction patients (CIRCUS study)
|
Summary
|
|
EudraCT number |
2009-013713-99 |
Trial protocol |
FR BE ES |
Global end of trial date |
28 Jun 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
21 Aug 2019
|
First version publication date |
21 Aug 2019
|
Other versions |
|
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 |
2009-559
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01502774 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Hospices Civils de Lyon
|
||
Sponsor organisation address |
3 Quai des Célestins, Lyon, France,
|
||
Public contact |
Valerie PLATTNER, Hospices Civils de Lyon, +33 4 72115213, valerie.plattner@chu-lyon.fr
|
||
Scientific contact |
Valerie PLATTNER, Hospices Civils de Lyon, +33 4 72406840, valerie.plattner@chu-lyon.fr
|
||
|
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 |
17 Sep 2015
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
27 Mar 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
28 Jun 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of the study is to determine whether Cyclosporine A, administered immediately prior to PCI reperfusion improves clinical outcomes in STEMI patients at 12 months
|
||
Protection of trial subjects |
Quality of life questionnaire measuring pain and anxiety
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Apr 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 |
Spain: 40
|
||
Country: Number of subjects enrolled |
Belgium: 46
|
||
Country: Number of subjects enrolled |
France: 884
|
||
Worldwide total number of subjects |
970
|
||
EEA total number of subjects |
970
|
||
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) |
635
|
||
From 65 to 84 years |
308
|
||
85 years and over |
27
|
||
|
||||||||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
Depending on each country and local procedures in the management of AMI, patients may be considered eligible by the local emergency units (SAMU in France, emergency rooms …) after verification of eligibility criteria and exclusion criteria (pre-screening). The pre-hospital MD briefly informed the patients about the study. | |||||||||||||||||||||||||||
|
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 |
Investigator, Subject | |||||||||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
|
Arm title
|
Cyclosporin | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Cyclosporine A
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Emulsion for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
|||||||||||||||||||||||||||
Dosage and administration details |
All patients will receive an intravenous bolus of 2.5 mg/kg per day of cyclosporine A. The injection will be performed slowly over 2 to 3 minutes.
|
|||||||||||||||||||||||||||
|
Arm title
|
Placebo | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Emulsion for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
|||||||||||||||||||||||||||
Dosage and administration details |
All patients will receive an intravenous bolus of 2.5 mg/kg per day of cyclosporine A. The injection will be performed slowly over 2 to 3 minutes.
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cyclosporin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Cyclosporin
|
||
Reporting group description |
- | ||
Reporting group title |
Placebo
|
||
Reporting group description |
- | ||
Subject analysis set title |
Full Analysis Set
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
includes all patients who were randomized, have received the study treatment, except those without informed consent, or without any legal protection measure, or without any data post randomization.
|
||
Subject analysis set title |
Safety Set
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
all patients randomized to a study treatment who received any amount of a planned study medication.
|
||
|
||||||||||
End point title |
combined incidence of “total mortality, hospitalization for heart failure, and LV remodelling | |||||||||
End point description |
||||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
1 year
|
|||||||||
|
||||||||||
Statistical analysis title |
Logistic mixted effect regression model | |||||||||
Comparison groups |
Cyclosporin v Placebo
|
|||||||||
Number of subjects included in analysis |
791
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.774 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.04
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.78 | |||||||||
upper limit |
1.39 | |||||||||
Variability estimate |
Standard deviation
|
|||||||||
|
|||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
At 1, 3, 6 and 12 months
|
||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||
Reporting group title |
Cyclosporin A
|
||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
09 Jul 2010 |
Amendment n°1:
Modification of IMP : CicloMulsion® instead of Sandimmun®
Modification of the principal judgement criterion and of the statistical analysis plan |
||
29 Nov 2010 |
Amendment n°2:
Update of participating investigator sites
Addition of one non eligibility criteria
Revision of patient’s information letter
|
||
14 Apr 2011 |
Amendment n°3:
Update of participating investigator sites
|
||
27 Jun 2011 |
Amendment n°4:
Update of participating investigator sites
Addition of two blood samples
|
||
09 Sep 2011 |
Amendment n°5:
Update of participating investigator sites
|
||
30 Nov 2011 |
Amendment n°6:
Collection of informed consent according to emergency situations
Revision of eligibility criteria
Revision of secondary objectives and end points wording
General information details |
||
22 Mar 2012 |
Amendment n°7:
Extension of the recruitment period
Transfer from principal to sub-study of one secondary endpoint
Modification of the stopping rules relative to the interim safety analysis
Update of participating investigator sites
General information details
|
||
12 Sep 2012 |
Amendment n°8:
Modification of one non eligibility criteria
Extension of time to perform the first echocardiogram
Modification of the injection duration
Update of participating investigator sites
|
||
15 Jul 2013 |
Amendment n°9:
Extension of the recruitment period (1 year more)
Modification of the delay for phone call (1 week to 2 weeks)
Update of principal investigator in Montpellier
General information details
|
||
28 Jan 2014 |
Amendment n°10:
Follow-up extension during 2 additional years.
Update of participating investigator sites.
Update the investigator brochure version
|
||
11 Mar 2014 |
Amendment n°11:
Modification of the quality of life questionnaire for the 3-year visit: EQ-5D-3L .
Addition of a patient card.
General information details in flowchart
Update of principal investigator in Mulhouse |
||
12 Dec 2014 |
Amendment n°12:
Update of secondary objectives, secondary end-points, and statistical analysis according to SAP
Update of the responsible team of the statistical analysis
Delete Bourges and Hopital Georges Pompidou centres
Update of principal investigator in Toulouse and Nancy
Clarification of principal investigator in Brest, Compiègne, Rouen, Lyon
General information details in flowchart
Update contact information for the sponsor
|
||
22 Jan 2015 |
Amendment n°13:
Correction of inclusion criteria #4: From “> 0.2 mV” to “≥ 0.2 mV” according to European Society of Cardiology and American Heart Association guidelines.
|
||
23 Jun 2015 |
Amendment n°14:
Addition of a second addendum version: proposed to the patient by phone.
Addendum modification: possibility to recover the data a posteriori in case of late addendum signature.
Update of principal investigator in Massy
|
||
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. | |||
| None reported | |||
