CRP Apheresis in STEMI

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

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 Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction; Myocardial Injury; Apheresis; C-Reactive Protein
• Intervention / Treatment: Device: Selective CRP apheresis using the PentraSorb®-CRP system

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastian J Reinstadler, MD, PhD; Phone Number: +43 (0) 512 504 25665; Email: sebastian.reinstadler@gmail.com
• Study Contact Backup: Name: Ivan Lechner, MD, PhD; Phone Number: +43 (0) 512 504 25665; Email: ivan.lechner@tirol-kliniken.at

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • University Clinic for Cardiology and Nephrology, Medical University of Graz
    • Contact: Heiko Bugger, MD
    • Principal Investigator: Heiko Bugger, MD
    • Sub-Investigator: Kathrin Eller, MD
  • Innsbruck, Austria, 6020
    • Recruiting
    • University Clinic of Internal Medicine III, Cardiology and Angiology. University Clinic of Internal Medicine IV, Nephrology and Hypertensiology. University Clinic of Radiology.
    • Contact: Sebastian J Reinstadler, MD, PhD; Email: sebastian.reinstadler@gmail.com
    • Sub-Investigator: Gert Klug, MD
    • Sub-Investigator: Andreas Kronbichler, MD, PhD
    • Sub-Investigator: Agnes Mayr, MD
    • Sub-Investigator: Martin Reindl, MD, PhD
    • Sub-Investigator: Ivan Lechner, MD
    • Sub-Investigator: Christina Tiller, MD
    • Sub-Investigator: Magdalena Holzknecht, MD
    • Sub-Investigator: Philipp Gauckler, MD
    • Sub-Investigator: Sara Denicolò, MD
    • Sub-Investigator: Bernhard Metzler, MD, MSc
    • Sub-Investigator: Axel Bauer, MD
    • Sub-Investigator: Gert Mayer, MD
    • Sub-Investigator: Elke Gizewski, MD
  • Salzburg, Austria, 5020
    • Not yet recruiting
    • University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg
    • Contact: Lukas J Motloch, MD, PhD
    • Principal Investigator: Lukas J Motloch, MD, PhD
• Germany
  • Leipzig, Germany, 04289
    • Recruiting
    • Leipzig Heart Center
    • Contact: Hans-Josef Feistritzer, MD, PhD
    • Principal Investigator: Holger Thiele, MD
    • Sub-Investigator: Hans-Josef Feistritzer, MD, PhD
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Not yet recruiting
      • Medical Clinic II - University Heart Center Lübeck
      • Contact: Thomas Stiermaier, MD
      • Principal Investigator: Ingo Eitel, Prof.
      • Sub-Investigator: Thomas Stiermaier, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.
No Intervention: Standard of care according to current guideline recommendations

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University Innsbruck
• Investigators: Principal Investigator: Sebastian J Reinstadler, MD, PhD, University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cardiac magnetic resonance imaging
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: 20210121-2475

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No