CRP Apheresis in STEMI

Study Overview
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Brief Summary
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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.

Official Title
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Selective C-reactive Protein Apheresis in ST-elevation Myocardial Infarction

Conditions
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ST Elevation Myocardial Infarction, C-Reactive Protein, Apheresis, Myocardial Injury

Intervention / Treatment
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* Device: Selective CRP apheresis using the PentraSorb®-CRP system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Symptoms consistent with STEMI with beginning greater than 30 minutes but less than 12 hours prior to primary percutaneous coronary intervention (PCI) CRP elevation of ≥7 mg/l measured between 6 to 16 hours after primary PCI Eligible for primary PCI Age ≥18 years Written informed consent Exclusion Criteria: Prior acute myocardial infarction, coronary artery bypass surgery or PCI. Persistent hemodynamic instability (Killip class >2 including cardiogenic shock) or resuscitated cardiac arrest not allowing a CMR scan. The patient is febrile (temperature >38°C) or has experienced an acute infection with fever in the last 14 days. CRP >15 mg/l at time of hospital admission. Chronic inflammatory disease. Known history of severe hepatic failure Chronic kidney disease with a creatinine clearance <30ml/min./1.73m² Contraindication to CMR. Pre-STEMI life expectancy of <1 year Participation in another interventional trial Limited possibility to join the follow-up examinations (e.g. patient lives abroad) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selective CRP apheresis as an adjunct to standard of care<br>Apheresis using the PentraSorb®-CRP system will be performed at day 1, 2 and 3 after PCI. | Device: Selective CRP apheresis using the PentraSorb®-CRP system<br>* 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.<br>|
| No Intervention: Standard of care according to current guideline recommendations<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary efficacy endpoint | Infarct size expressed as % of left ventricular myocardial mass (LVMM) as visualized by cardiac magnetic resonance (CMR) imaging at 5 ± 2 days post PCI | 5 ± 2 days post PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoint | Adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization for the index event | during hospitalization for the index event | 
| All-cause mortality or hospitalization for heart failure 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) | within 12 months after randomization | 
| CMR endpoints defined as: Left ventricular ejection fraction and microvascular obstruction and exploratory (intramyocardial hemorrhage, edema extent, myocardial salvage, native T1 mapping, strain) | 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. | at baseline, 4 months and 12 months after PCI for STEMI | 
| Hospitalization for heart failure within 12 months after randomization |  | within 12 months after randomization | 
| Cardiovascular mortality at 12 months |  | within 12 months after randomization | 
| CRP concentrations | CRP concentrations during index hospitalization | during hospitalization for the index event | 
| 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 | 
| Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide) |  | at baseline, 4 months, 12 months post PCI | 
| Renal function (eGFR) | as measured by the MDRD and CKD-EPI formula | during hospitalization for the index event | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac magnetic resonance imaging