ST-elevation myocardial infarction (STEMI) Circulatory System Acute myocardial infarction
Conditions
Interventions
The safety and efficacy of KAND567 vs placebo will be investigated in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention.
Participants who are suitable
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Reperfusion of anterior MI expected within 5 hours of onset of acute chest pain 2. Diagnosis of acute myocardial infarction with ST elevation at the J-point in two contiguous leads by ECG (V1-V4 at least two contiguous leads STE 2.0 mm in men and 1.5 mm in women) 3. Agreement to undergo routine procedure of PPCI 4. Aged =18-75 years 5. Willingness and ability to comply with trial procedures, visit schedules, trial restrictions and requirements 6. Confirmation of anterior STEMI (TIMI 0-2 flow) by angiography and occlusion of proximal or mid LAD (segments 5 or 6) 7. Verbal consent to take part in the trial is given
Exclusion criteria
Exclusion criteria: 1. Anyone with known cognitive impairment or unable to provide verbal consent 2. Serious co-existing medical condition, including known hepatic failure and known renal failure with known eGFR <30 ml/min/m² or severe mental disorder, known at the time of randomisation 3. Cardiogenic shock, non-compensated acute heart failure and/or pulmonary edema 4. Previous known major vascular intervention within the last 4 weeks 5. History of previous myocardial infarction (MI) in the LAD 6. Documented left ventricular systolic dysfunction (EF <40%) 7. Previous coronary artery bypass grafting (CABG) 8. Patients unable to tolerate or undergo MRI scanning including patients with claustrophobia, cardiac pacemaker/defibrillator, ferromagnetic metal implants unless approved for use in MRI scanners or excessive body weight 9. Known planned hospitalisations (e.g. elective surgery), or other scheduled treatment for pre-existing conditions during the course of the trial that could interfere with clinical assessment 10. Known allergy to contrast agent or other contraindications for angiography 11. Any known previous diagnosis of invasive cancer within the last 5 years except for treated basal cell carcinoma of the skin 12. Current use of steroids or immunosuppressants 13. Current use of benzodiazepines 14. Current use of ticagrelor (unable to switch to Prasugrel on trial entry) 15. Known pre-existing severe liver disease, including chronic hepatitis or alcohol-dependent liver cirrhosis 16. Other medical or social reasons for exclusion at the discretion of the investigator 17. Administration of any investigational drug within 3 months of trial medication, as far as known to the patient 18. Current use of drug sensitive to CYP3A4 inhibition which cannot be paused or switched to an alternative from the same class of medication for the period of IMP administration, including: 18.1. Certain P2Y12 inhibitors (clopidogrel) 18.2. Certain statins (lovastatin and simvastatin) 19. Women of child-bearing potential who are sexually active who are not using a contraceptive method with a failure rate of <1% to prevent pregnancy prior to trial entry. Postmenopausal women must be amenorrhoeic for at least 12 months prior to randomisation to be considered of non-childbearing potential 20. Women of child-bearing potential who are not willing to use a contraceptive method with a failure rate of <1% to prevent pregnancy throughout the trial 21. Male patients with female partners of childbearing potential not willing to use effective contraception 22. Male patients must agree to refrain from donating sperm whilst participating in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety and tolerability of KAND567 will be assessed on the following: 1. Occurrence of adverse events (AEs) during the 90 days trial participation 2. Changes in vital signs between baseline and 90 days 3. Any change in safety bloods including blood chemistry, haematology and urinalysis will be measured over the period that the participant is in hospital. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. CD3+CX3CR1+ effector memory T-lymphocytes, quantified in non-coronary arterial or venous blood and measured by the BD TruCount assay and flow cytometry, from baseline up to 4 days 2. Levels of inflammatory markers including high-sensitivity CRP and IL-6 measured using laboratory analysis of blood samples at timepoints from baseline up until 90 days 3. CX3CR1 receptor density on the cell surface of T cells, monocytes and NK-cells measured using laboratory analysis of blood samples at baseline, and at set timepoints until the end of IMP administration 4. The following outcomes will be measured at 72 hours and 90 days using cardiac MRI: 4.1. The myocardial salvage index (MSI) (area at risk/absolute infarct size) (72 hours only) 4.2. Infarct size 4.3. Ejection fraction 4.4. Potential Improved left ventricular remodelling (lower delta end systolic volume and delta end diastolic volume, separately) 5. The pharmacokinetic parameters steady-state concentration (Css) and minimum plasma concentration (Cmin) measured using laboratory analysis of blood samples at time points from immediately prior to reperfusion up to 4 days 6. ST-segment resolution measured by ECG 60 minutes post reperfusion 7. Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) measured by cardiac MRI performed at 72 hours 8. Neutrophil and leukocyte counts from full blood analysis conducted at 24 hours, 48 hours and 72 hours | — |
Countries
England, United Kingdom
Contacts
Public ContactKaren Nicholson
Outcome results
None listed