Apheresis, C-Reactive Protein, Myocardial Injury, ST Elevation Myocardial Infarction
Conditions
Keywords
Cardiac magnetic resonance imaging
Brief summary
Background: In patients with acute ST-elevation myocardial infarction (STEMI), the amount of infarcted myocardium (infarct size) is known to be a major predictor for adverse remodeling and recurrent adverse cardiovascular events. Effective cardio-protective strategies with the aim of reducing infarct size are therefore of great interest. Local and systemic inflammation influences the fate of ischemic myocardium and thus, adverse remodeling and clinical outcome. C-reactive protein (CRP) also acts as a potential mechanistic mediator that adversely affects the amount of irreversible myocardial tissue damage after acute myocardial infarction. Objective: The main objectives of the current study are to investigate the efficacy of selective CRP apheresis, using the PentraSorb®-CRP system, as an adjunctive therapy to standard of care for patients with acute STEMI treated with primary PCI. Design: Investigator-initiated, prospective, randomized, open-label (outcome assessors masked), controlled, multicenter, two group trial with a two-stage adaptive design. Innovation: Selective CRP apheresis offers potential to decrease infarct size and consequently improve outcome after PCI for STEMI. This is the first randomized trial investigating the impact of selective CRP apheresis on infarct size in post-STEMI patients. In perspective, the study design allows furthermore to collect robust evidence for the design of a definitive outcome study.
Interventions
DEVICESelective CRP apheresis using the PentraSorb®-CRP system
Selective CRP apheresis as an adjunct to standard of care. Apheresis using the PentraSorb®-CRP system will be performed at day 1, 2 and 3 after PCI.
Sponsors
Medical University Innsbruck
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of first acute STEMI in accordance with the European Society of Cardiology (ESC) Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation 2. Symptoms consistent with STEMI with beginning greater than 30 minutes but less than 12 hours prior to primary percutaneous coronary intervention (PCI) 3. CRP elevation of ≥7 mg/l measured between 6 to 16 hours after primary PCI 4. Eligible for primary PCI 5. Age ≥18 years 6. Written informed consent
Exclusion criteria
1. Prior acute myocardial infarction, coronary artery bypass surgery or PCI. 2. Persistent hemodynamic instability (Killip class \>2 including cardiogenic shock) or resuscitated cardiac arrest not allowing a CMR scan. 3. The patient is febrile (temperature \>38°C) or has experienced an acute infection with fever in the last 14 days. 4. CRP \>15 mg/l at time of hospital admission. 5. Chronic inflammatory disease. 6. Known history of severe hepatic failure 7. Chronic kidney disease with a creatinine clearance \<30ml/min./1.73m² 8. Contraindication to CMR. 9. Pre-STEMI life expectancy of \<1 year 10. Participation in another interventional trial 11. Limited possibility to join the follow-up examinations (e.g. patient lives abroad) 12. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary efficacy endpoint | 5 ± 2 days post PCI | Infarct size expressed as % of left ventricular myocardial mass (LVMM) as visualized by cardiac magnetic resonance (CMR) imaging at 5 ± 2 days post PCI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoint | during hospitalization for the index event | Adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization for the index event |
| All-cause mortality or hospitalization for heart failure within 12 months after randomization | within 12 months after randomization | All-cause mortality or hospitalization for heart failure within 12 months after randomization (endpoint of interest with respect to the two-stage adaptive design) |
| CMR endpoints defined as: Left ventricular ejection fraction and microvascular obstruction and exploratory (intramyocardial hemorrhage, edema extent, myocardial salvage, native T1 mapping, strain) | at baseline, 4 months and 12 months after PCI for STEMI | CMR endpoints will be assessed at baseline, 4 and 12 months CMR follow-up study and are defined according to the Journal of American College of Cardiology Scientific Expert Consensus document. |
| Hospitalization for heart failure within 12 months after randomization | within 12 months after randomization | — |
| Cardiovascular mortality at 12 months | within 12 months after randomization | — |
| Left ventricular thrombus formation | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Biomarker concentrations of myocardial necrosis (enzymatic infarct size; high-sensitivity troponin T) | at baseline, 4 months, 12 months post PCI | — |
| CRP concentrations | during hospitalization for the index event | CRP concentrations during index hospitalization |
| Renal function (eGFR) | during hospitalization for the index event | as measured by the MDRD and CKD-EPI formula |
| Renal function (Cystatin C-based calculation of creatinine clearance) | during hospitalization for the index event | — |
| Cardiac autonomic function: Deceleration capacity of heart rate | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Cardiac autonomic function: Heart rate variability | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Cardiac autonomic function: Periodic repolarization dynamics | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Cardiac autonomic function: Baroreflex sensitivity | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Cardiac autonomic function: Skin sympathetic nerve activity | 5 ± 2 days, 4 months, 12 months post PCI | — |
| Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide) | at baseline, 4 months, 12 months post PCI | — |
Countries
Austria, Germany
Contacts
Primary ContactSebastian J Reinstadler, MD, PhD
Backup ContactIvan Lechner, MD, PhD
Outcome results
None listed