Myocardial ischemia/reperfusion injury
Conditions
Interventions
Trade Name: Sandimmun (concentrate for solution for infusion 50mg/ml)
Product Name: N/A
Product Code: N/A
Pharmaceutical Form: Concentrate for solution
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients presenting with acute myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (primary PCI) 2. Age above 18 years 3. Presenting within 6 hours of the onset chest pain and ST segment elevation. The culprit coronary artery has to be a major coronary artery with a diameter of at least 3mm and has to be proximally occluded (TIMI flow grade 0-1) at the time of admission coronary angiography Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: 1. Patients with any disorder associated with immunological dysfunction (acute or chronic inflammatory or neoplastic co-existing disease, known positive serology for HIV, or hepatitis) 2. Clinically unstable patients (haemodynamically unstable, cardiogenic shock, unconscious patients) 3. Patients with evidence of coronary collaterals to the infarct area 4. Patients with an open (TIMI > 1) culprit coronary artery at the time of angiography. 5. Previous myocardial infarction 6. Previous thrombolytic therapy 7. Patients with known hypersensitivity to ciclosporin or to egg, peanut or soya-bean proteins. 8. Patients with known renal insufficiency (either known GFR 180/110 mmHg) 11. Patients treated with any compound containing hypericum perforatum, stiripentol, Aliskiren, Bosentan or Rosuvastatin or with an active treatment that might modify blood concentration of ciclosporin. 12. Female patients currently pregnant or women of childbearing age who are not using contraception (verbal diagnosis). Female patients of childbearing potential who are using contraception but are subsequently found to have a positive urine pregnancy test (pregnancy test performed as soon as reasonably practicable after IMP administration). 13. Contraindication to cardiac MRI: - Pacemaker - Implantable defibrillator 14. Patients unable to undergo cardiac MRI for any of the following reasons: - Frailty – as judged by the clinician. Frailty is defined as meeting three out of the five following criteria: low grip strength, low energy, slowed walking speed, low physical activity and/or unintentional weight loss. Due to the tight time constraints and emergency setting of this trial the clinician cannot test all these parameters and will need to exercise their judgment. - Claustrophobic - patients who cannot take elevators or who are afraid of narrow or enclosed spaces. - Breathlessness - patients who suffer from breathlessness at rest or low exercise level (e.g. while walking on the level). 15. Use of other investigational study drugs within 30 days prior to trial entry (defined as date of randomisation into trial). Co-enrolment with other studies is not allowed. 16. Lack of capacity to give initial verbal consent 17. Life expectancy <1year due to non-cardiac illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Infarct size at 12 weeks post-PPCI as measured by cardiac resonance imaging (MRI). Infarct size will be calculated as the percent of infarcted myocardium per left ventricular (LV) mass.;Timepoint(s) of evaluation of this end point: 12-weeks post-PPCI;Main Objective: Routine angioplasty treatment for a heart attack involves opening a blocked artery with a balloon then inserting a small metal scaffold (stent) to hold the artery open. During this procedure inflammation can occur causing further damage to the heart. The objective of this trial is determine whether administration of the drug ciclosporin at the start of the angioplasty procedure reduces the amount of damage to the heart. The damage to the heart will be assessed after 12 weeks by an MRI scan. ; Secondary Objective: 1) To determine the effect of the drug ciclosporin given prior to restoring blood flow to the heart by primary angioplasty on microvascular obstruction (blocked arteries) relative to treatment with a 'dummy' drug (placebo). This will be assessed from a cardiac MRI scan taken after 2-7 days. 2) To determine the effect of the drug ciclosporin given prior to restoring blood flow to the heart by primary angioplasty on the size of the heart attack relative to treatment with a 'dummy' drug (placebo). This will be assessed from a cardiac MRI scan taken after 2-7 days. 3) To determine the effect of the drug ciclosporin given to patients prior to restoring blood flow to the heart by angioplasty on inflammation (T-cell count) relative to treatment with a 'dummy' drug (placebo). T-cells will be measured in blood samples taken at 0, 5, 15, 30 and 90 minutes after blood flow has been restored. 4)To determine the effect of the drug ciclosporin given prior to restoring blood flow to the heart b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Microvascular obstruction after 2-7 days as measured by a single cardiac MRI scan 2. Salvage index after 2-7 days as measured by a single cardiac MRI scan 3. Change in T lymphocyte counts relative to baseline at 5, 15, 30 and 90 minutes post-reperfusion 4. Number of clinical events (all cause deaths, stroke or myocardial infarction) after 12 months ; Timepoint(s) of evaluation of this end point: 1. Timepoint of single cardiac MRI scan taken between 2 and 7 days post-PPCI 2. Timepoint of single cardiac MRI scan taken between 2 and 7 days post-PPCI 3. 5, 15, 30 and 90 minutes post-reperfusion 4. 12 months | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Ioakim Spyridopoulos
Newcastle University
Outcome results
None listed