CRP Apheresis in STEMI

Official title

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

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.

Interventions

• Device Selective 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.

Primary outcome measures

• Primary efficacy endpoint [Time frame: 5 ± 2 days post PCI]

Secondary outcome measures (12)

• Safety endpoint [Time frame: during hospitalization for the index event]
• All-cause mortality or hospitalization for heart failure within 12 months after randomization [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) [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 [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) [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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Austria · 3 centers

• University Clinic for Cardiology and Nephrology, Medical University of Graz — Graz
• University Clinic of Internal Medicine III, Cardiology and Angiology. University Clinic of — Innsbruck
• University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg — Salzburg

Germany · 2 centers

• Medical Clinic II - University Heart Center Lübeck — Lübeck
• Leipzig Heart Center — Leipzig

Publications

• Reinstadler SJ, Kronbichler A, Reindl M, Tiller C, Holzknecht M, Oberhollenzer F, Kaser A, Gauckler P, Stiermaier T, Feistritzer HJ, Mayr A, Gizewski ER, Rezar R, Bugger H, Eller K, Eitel I, Schneider S, Mayer G, Thiele H, Bauer A, Metzler B, Lechner I; CRP-STEMI Investigators. Selective C-reactive protein apheresis in ST-elevation myocardial infarction: Design and rationale of the randomized CRP- PMID 40738310

Identifiers

NCT: NCT04939805 · 20210121-2475

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗