E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute myocardial infarction |
|
E.1.1.1 | Medical condition in easily understood language |
acute myocardial infarction |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | 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 AMI patients |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are:
- to determine whether cyclosporine A, administered immediately prior to PCI reperfusion has an effect on:
1)mortality events following AMI (at 30 days,1 year and 3 years)
2)Cardiac and vascular events following AMI
3) Cardiac prognostic factors
4)Quality of life
To describe the tolerance of medicinal investigational products.
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The principal investigators of each of these sub-studies will have to develop a specific sub-study protocol and submit it first to approval to the Steering Committee, and afterwards to approval of local authorities and the IEC (independent ethic committee).
The main sub-studies that were already submitted and approved by the Steering Committee are listed below:
1/ study of adiponectin (Principal Investigator: Dr. Marc Claeys, belgium)
Adiponectin will be measured in an estimated number of 256 patients in the control group in order to assess relation between adiponectin levels and occurrence of reperfusion injury. Comparisons will be made between an estimated 64 patients in the low quartile of adiponectin vs. the others, as well as interaction with the study treatment. This sub-study will be linked to the bio-bank.
2/ MRI substudy
Assessment of the effect of cyclosporine treatment of infarct size and microvascular obstruction (MVO: no reflow) by MRI.
3/ cyclophilin D (Principal Investigator: Dr. Michel Ovize, France)
Objective: to determine whether circulating cypD may be a marker that may predict infarct size. This sub-study will be linked to the bio-bank
4/ genetic association study
Centralised genetic samples will be collected in an ancillary study.
|
|
E.3 | Principal inclusion criteria |
1. All (male and female) patients, aged over 18, without any legal protection measure
2. Having a health coverage
3. Presenting within 12 hours of the onset of chest pain,
4. Who have ST segment elevation > 0.2 mV in two contiguous leads,
5. For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI).
And (further inclusion criteria to be confirmed by the admission coronary-angiography)
6. The culprit coronary artery has to be the LAD
7. The LAD artery has to be occluded (TIMI flow grade 0-1) at the time of admission coronary angiography.
8. Preliminary oral informed consent followed by signed informed consent as soon as possible.
Patients undergoing either primary PCI or rescue PCI are eligible for the study. Patients with previous AMI, PCI or coronary artery bypass surgery (CABG) are eligible for the study.
|
|
E.4 | Principal exclusion criteria |
1. Patients with loss of consciousness or confused
2. Patients with cardiogenic shock
3. Patients with the left circumflex or the right coronary artery (RCA) as the culprit artery, or with evidence of coronary collaterals to the risk region
4. Patients with an opened (TIMI > 1) LAD coronary artery at admission on initial (admission) coronary angiography
5. Patients with
- known hypersensitivity to cyclosporine
- known renal insufficiency (either known creatinin clearance < 30 ml/min/1.73m² or current medical care for severe renal insufficiency)
- known liver insufficiency
- uncontrolled (treated or untreated) hypertension (> 180/110 mmHg)
6. Patients treated with any compound containing Hypericum perforatum (St.-John’s-worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine
7. Female patients currently pregnant or women of childbearing age who were not using contraception (oral diagnosis).
8. Patients with any disorder associated with immunological dysfunction more recently than 6 months prior to presentation
- cancer, lymphoma
- known positive serology for HIV, or hepatitis |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Combined incidence of [total mortality; hospitalization for heart failure; LV remodelling (increase of LV end-diastolic volume >15%)] at one year post-AMI |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1)Combined incidence of [total mortality; hospitalization for heart failure; LV remodelling (increase of LV end-diastolic volume >15%)] at three years post-AMI.
2)The survival free of any major cardiovascular adverse event [all-cause mortality, rehospitalisation for heart failure, re-infarction, unstable angina, stroke] at three years post-AMI.
- Mortality events :
3) All causes of mortality
4) Cardiovascular deaths
- Cardiac and vascular events :
5) Heart failure: 1) in-hospital worsening of heart failure after reperfusion, 2) re-hospitalization for: a) worsening of a heart failure existing at admission, b) appearance of “new” heart failure
6) Myocardial infarction
7) Unstable angina
8) Stroke
9) LV remodelling
10)Infarct size, LVEF, LVEDV, LVESV will be assessed at acute and chronic phases (> 6 months) cardiac MRI studies, only for patients included in participating centers where cardiac MRI is part of the usual post-infarct care.
11)Quality of life at three years
12)NT-pro BNP levels at three years
- Cardiac prognostic factors :
1. Infarct size: peak Troponin (T or I)
2. LV function at one year
3. Microvascular obstruction (no reflow)
- Tolerance to medicinal investigational products
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 30 days and 1 year for mortality events
- 3 years for other end points |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 49 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 93 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 93 |