CRP Apheresis in STEMI

• ClinicalTrials.gov Identifier: NCT04939805
• Recruitment Status: Recruiting
• First Posted: June 25, 2021
• Last Update Posted: July 13, 2022
• Sponsor: Medical University Innsbruck
• Information provided by (Responsible Party): Medical University Innsbruck

Study Description

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.

Condition or disease	Intervention/treatment	Phase
ST Elevation Myocardial Infarction; C-Reactive Protein; Apheresis; Myocardial Injury	Device: Selective CRP apheresis using the PentraSorb®-CRP system	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 202 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Selective C-reactive Protein Apheresis in ST-elevation Myocardial Infarction
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: March 31, 2024
• Estimated Study Completion Date: March 31, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Primary efficacy endpoint [ Time Frame: 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 Outcome Measures :

1. Safety endpoint [ Time Frame: during hospitalization for the index event ]
   Adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) during hospitalization for the index event
2. All-cause mortality or hospitalization for heart failure within 12 months after randomization [ Time Frame: 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)
3. 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 ]
   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.
4. Hospitalization for heart failure within 12 months after randomization [ Time Frame: within 12 months after randomization ]
5. Cardiovascular mortality at 12 months [ Time Frame: within 12 months after randomization ]
6. CRP concentrations [ Time Frame: during hospitalization for the index event ]
   CRP concentrations during index hospitalization
7. Left ventricular thrombus formation [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]
8. Biomarker concentrations of myocardial necrosis (enzymatic infarct size; high-sensitivity troponin T) [ Time Frame: at baseline, 4 months, 12 months post PCI ]
9. Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide) [ Time Frame: at baseline, 4 months, 12 months post PCI ]
10. Renal function (eGFR) [ Time Frame: during hospitalization for the index event ]
    as measured by the MDRD and CKD-EPI formula
11. Renal function (Cystatin C-based calculation of creatinine clearance) [ Time Frame: during hospitalization for the index event ]
12. Cardiac autonomic function: Deceleration capacity of heart rate [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]
13. Cardiac autonomic function: Heart rate variability [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]
14. Cardiac autonomic function: Periodic repolarization dynamics [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]
15. Cardiac autonomic function: Baroreflex sensitivity [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]
16. Cardiac autonomic function: Skin sympathetic nerve activity [ Time Frame: 5 ± 2 days, 4 months, 12 months post PCI ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Sebastian J Reinstadler, MD, PhD; +43 (0) 512 504 25665; sebastian.reinstadler@gmail.com

Contact: Ivan Lechner, MD; +43 (0) 512 504 25665; ivan.lechner@tirol-kliniken.at

Locations

Austria

University Clinic for Cardiology and Nephrology, Medical University of Graz; Not yet recruiting

Graz, Austria, 8036

Contact: Heiko Bugger, MD

Principal Investigator: Heiko Bugger, MD

Sub-Investigator: Kathrin Eller, MD

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

Innsbruck, Austria, 6020

Contact: Sebastian J Reinstadler, MD, PhD 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

University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg; Not yet recruiting

Salzburg, Austria, 5020

Contact: Lukas J Motloch, MD, PhD

Principal Investigator: Lukas J Motloch, MD, PhD

Germany

Medical Clinic II - University Heart Center Lübeck; Not yet recruiting

Lübeck, Schleswig-Holstein, Germany, 23538

Contact: Thomas Stiermaier, MD

Principal Investigator: Ingo Eitel, Prof.

Sub-Investigator: Thomas Stiermaier, MD.

Leipzig Heart Center; Not yet recruiting

Leipzig, Germany, 04289

Contact: Hans-Josef Feistritzer, MD, PhD

Principal Investigator: Holger Thiele, MD

Sub-Investigator: Hans-Josef Feistritzer, MD, PhD

Sponsors and Collaborators

Medical University Innsbruck

Investigators

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

More Information

• Responsible Party: Medical University Innsbruck
• ClinicalTrials.gov Identifier: NCT04939805
• Other Study ID Numbers: 20210121-2475
• First Posted: June 25, 2021
• Last Update Posted: July 13, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University Innsbruck:

Cardiac magnetic resonance imaging

Additional relevant MeSH terms:

Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases