Clinical Trial Results:
CYCLosporinE A in reperfused acute myocardial infarction (CYCLE)
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Summary
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EudraCT number |
2011-002876-18 |
Trial protocol |
IT |
Global end of trial date |
30 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Feb 2019
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First version publication date |
24 Feb 2019
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Other versions |
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Summary report(s) |
Cyclosporine A in Reperfused Myocardial Infarction |
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 |
2011-002876-18
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01650662 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Istituto di Ricerche Farmacologiche Mario Negri- IRCCS
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Sponsor organisation address |
Via Privata Giuseppe La Masa, 19, Milan, Italy, 20157
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Public contact |
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, +39 0239014454, cycle@marionegri.it
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Scientific contact |
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, +39 02 39014454, cycle@marionegri.it
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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 |
31 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jan 2015
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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 |
The primary objective of the present study is improvement of myocardial reperfusion, measured with ST-segment resolution >=70% 1 hour after PCI.
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Protection of trial subjects |
It was run according to the Declaration of Helsinki of Good Clinical Practice. Regulatory agencies and local ethics committees approved the study protocol. All patients gave written informed consent.
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Background therapy |
Recommended treatments according to STEMI European guidelines | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Italy: 410
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Worldwide total number of subjects |
410
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EEA total number of subjects |
410
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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) |
185
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From 65 to 84 years |
225
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 410 STEMI patients were enrolled from January 19, 2012, to April 30, 2014, in 31 Italian centers: 207 received an IV bolus of CsA, and 203, who served as controls, received conventional treatment. | |||||||||
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Pre-assignment
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Screening details |
- | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
410 | |||||||||
Number of subjects completed |
410 | |||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cyclosporine A | |||||||||
Arm description |
Cyclosporine A. The investigational active treatment is CsA, an immunosopressant indicated for the prevention of acute rejection after organ transplant, including cardiac transplantation. The preparation used in the trial will be Sandimmun IV, contening CsA 50 mg/ml, Cremophor EL and 94% ethyl alchool in a 5 ml vial. Patients will received Cyclosporine A on the top of recommend standard care of acute myocardial infarction. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Cyclosporine A
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Investigational medicinal product code |
25300
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Other name |
Sandimmune IV, Novartis, Basel, Switzerland
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
The bolus of 2.5 mg/kg of cyclosporine A was injected over 20 to 30 s into an antecubital vein after coronary angiography, but just before passage of the wire into the culprit artery (thus avoiding any wire-related dissolution/fragmentation of the occlusive thrombus), and at least 5 min before PCI, to allow distribution of the drug.
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Arm title
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Control group | |||||||||
Arm description |
The control group receveid on the top of recommended standared care of acute myocardial infarction. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Cyclosporine A
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Reporting group description |
Cyclosporine A. The investigational active treatment is CsA, an immunosopressant indicated for the prevention of acute rejection after organ transplant, including cardiac transplantation. The preparation used in the trial will be Sandimmun IV, contening CsA 50 mg/ml, Cremophor EL and 94% ethyl alchool in a 5 ml vial. Patients will received Cyclosporine A on the top of recommend standard care of acute myocardial infarction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
The control group receveid on the top of recommended standared care of acute myocardial infarction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cyclosporine A
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Reporting group description |
Cyclosporine A. The investigational active treatment is CsA, an immunosopressant indicated for the prevention of acute rejection after organ transplant, including cardiac transplantation. The preparation used in the trial will be Sandimmun IV, contening CsA 50 mg/ml, Cremophor EL and 94% ethyl alchool in a 5 ml vial. Patients will received Cyclosporine A on the top of recommend standard care of acute myocardial infarction. | ||
Reporting group title |
Control group
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Reporting group description |
The control group receveid on the top of recommended standared care of acute myocardial infarction. | ||
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End point title |
Incidence ST-segment resolution of 70% or more | ||||||||||||
End point description |
The primary endpoint was incidence of =/>70% ST-segment resolution 60 min after TIMI flow grade 3.
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End point type |
Primary
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End point timeframe |
One hour after PCI
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Statistical analysis title |
Logistic regression model | ||||||||||||
Statistical analysis description |
The primary endpoint (complete ST-segment resolution [i.e.,=/>70%, 60 min after PCI]) was analyzed with a logistic regression model. Adjustment was made by multivariable logistic regression for baseline characteristics (number of ECG leads with ST-segment deviation, ventricular tachycardia, and Rentrop score=/>2 unbalanced between the 2 groups.
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Comparison groups |
Cyclosporine A v Control group
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Number of subjects included in analysis |
394
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Confidence interval |
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End point title |
concentration of hs-cTnT | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
measured on day 4 after pPCI
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Statistical analysis title |
Wilcoxon non-paramentric test | ||||||||||||
Comparison groups |
Cyclosporine A v Control group
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Number of subjects included in analysis |
346
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
All cause mortality or Heart Failure or cardiogenic shock | |||||||||
End point description |
Rehospitalization for cardiovascular reasons, all cause and cardiovascular death, heart failure, and cardiogenic shock
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End point type |
Secondary
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End point timeframe |
From entry to 6 months follow-up
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Statistical analysis title |
Kaplan-Meier method | |||||||||
Comparison groups |
Cyclosporine A v Control group
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Number of subjects included in analysis |
410
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Regression, Cox | |||||||||
Confidence interval |
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End point title |
Regional left ventricular function | ||||||||||||
End point description |
Left ventricular akinetic and dyskinetic segments were assessed by echocardiography.
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End point type |
Secondary
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End point timeframe |
day 4 and 6 months
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Statistical analysis title |
Student t-test | ||||||||||||
Comparison groups |
Cyclosporine A v Control group
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Number of subjects included in analysis |
361
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Global left ventricular function | ||||||||||||
End point description |
Left ventricular ejection fraction assessed by ecocargiography
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End point type |
Secondary
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End point timeframe |
Day 4 and 6 months follow up
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Statistical analysis title |
Student t test | ||||||||||||
Comparison groups |
Control group v Cyclosporine A
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Number of subjects included in analysis |
361
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
From entry to 6 months follow-up
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Adverse event reporting additional description |
Only 1 serious adverse drug reaction was reported in the whole trial, a patient in the CsA group who died after surgery for myocardial rupture 23 days after the index MI
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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 |
16.0
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Reporting groups
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Reporting group title |
Cyclosporine A group
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Reporting group description |
- | ||||||||||||||||||||||
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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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14 Sep 2012 |
DSMB composition: new composition of the DSMB
Extension of the inclusion criteria for randomizzation: "All (male and female) patients, aged over 18, presenting with a large STEMI within 4 hours of onset (defined as angina pectoris or equivalent symptoms of more than 20 minutes duration within the last 4 hour..." was changed with: "All (male and female) patients, aged over 18, presenting with a large STEMI within 6 hours of onset (defined as angina pectoris or equivalent symptoms of more than 20 minutes duration within the last 6 hour..."
Type of randomization: "Central randomization in a 1:1 ratio will be performed by telephone call to the National Coordinating Centre" was changed with: "Central randomization will be performed in a 1:1 ratio."
Cyclosporine dosed:" 2.5mg of CsA" was changed with :" 2.5mg/kg of CsA"
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04 Mar 2013 |
Steering Committee composition: two components were added
Statistical and Data Management composition: 1 component was substituted
Duration of the study: recruitment period
"Start: September 1, 2011
End: February 28, 2013
The expected duration of the study for each subject is 6 months, for a total study duration of 24 months."was changed with:
"Start: September 1, 2011
End: February 28, 2014
Study duration
The expected duration of the study for each subject is 6 months, for a total study duration of 36 months."
Time of second ECG recording
"The primary end-point of ST resolution will be assessed by the ECG Core Lab. The core lab will receive from each Center an ECG tracing at randomization and another after 60 minutes for each patient enrolled to CYCLE." was changed with:
"The primary end-point of ST resolution will be assessed by the ECG Core Lab. The core lab will receive from each Center an ECG tracing at randomization and another after 60 minutes after the antegrade flow was observed, for each patient enrolled to CYCLE." |
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08 Jan 2014 |
Duration of the study: recruitment period
Recruitment period: "Start 1/09/2011
End 28/02/2014
End of follow-up: 30/08/2014
Data analysis: 30/10/2014" was changed with:
Recruitment period: "Start 1/09/2011
End 30/04/2014
End of follow-up: 31/10/2014
Data analysis: 31/12/2014" |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/26821623 |
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