CRP Apheresis in STEMI

Medical University Innsbruck202 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

202

Conditions

ST Elevation Myocardial Infarction

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Locations (5)

University Clinic for Cardiology and Nephrology, Medical University of Graz

Graz, Austria

RECRUITING

University Clinic of Internal Medicine III, Cardiology and Angiology. University Clinic of Internal Medicine IV, Nephrology and Hypertensiology. University Clinic of Radiology.

Innsbruck, Austria

RECRUITING

University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg

Salzburg, Austria

NOT_YET_RECRUITING

Medical Clinic II - University Heart Center Lübeck

Lübeck, Schleswig-Holstein, Germany

NOT_YET_RECRUITING

Leipzig Heart Center

Leipzig, Germany

RECRUITING

Outcomes

Primary Outcomes

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

Time frame: 5 ± 2 days post PCI

Secondary Outcomes

Safety endpoint

Adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization for the index event

Time frame: 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)

Time frame: 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.

Time frame: at baseline, 4 months and 12 months after PCI for STEMI

Hospitalization for heart failure within 12 months after randomization

Time frame: within 12 months after randomization

Cardiovascular mortality at 12 months

Time frame: within 12 months after randomization

CRP concentrations

CRP concentrations during index hospitalization

Time frame: during hospitalization for the index event

Left ventricular thrombus formation

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

Biomarker concentrations of myocardial necrosis (enzymatic infarct size; high-sensitivity troponin T)

Time frame: at baseline, 4 months, 12 months post PCI

Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide)

Time frame: at baseline, 4 months, 12 months post PCI

Renal function (eGFR)

as measured by the MDRD and CKD-EPI formula

Time frame: during hospitalization for the index event

Renal function (Cystatin C-based calculation of creatinine clearance)

Time frame: during hospitalization for the index event

Cardiac autonomic function: Deceleration capacity of heart rate

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

Cardiac autonomic function: Heart rate variability

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

Cardiac autonomic function: Periodic repolarization dynamics

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

Cardiac autonomic function: Baroreflex sensitivity

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

Cardiac autonomic function: Skin sympathetic nerve activity

Time frame: 5 ± 2 days, 4 months, 12 months post PCI

CRP Apheresis in STEMI

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts