CRP Apheresis in STEMI

ST Elevation Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04939805
• Other study ID #: 20210121-2475
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Medical University Innsbruck
• Contact: Sebastian J Reinstadler, MD, PhD
• Phone: +43 (0) 512 504 25665
• Email: sebastian.reinstadler[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 202
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Apheresis
• C-Reactive Protein
• Infarction
• Myocardial Infarction
• Myocardial Injury
• ST Elevation Myocardial Infarction

Intervention

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.

Locations

Country	Name	City	State
Austria	University Clinic for Cardiology and Nephrology, Medical University of Graz	Graz
Austria	University Clinic of Internal Medicine III, Cardiology and Angiology. University Clinic of Internal Medicine IV, Nephrology and Hypertensiology. University Clinic of Radiology.	Innsbruck
Austria	University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg	Salzburg
Germany	Leipzig Heart Center	Leipzig
Germany	Medical Clinic II - University Heart Center Lübeck	Lübeck	Schleswig-Holstein

Sponsors (1)

Lead Sponsor	Collaborator
Medical University Innsbruck

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Hospitalization for heart failure within 12 months after randomization		within 12 months after randomization
Secondary	Cardiovascular mortality at 12 months		within 12 months after randomization
Secondary	CRP concentrations	CRP concentrations during index hospitalization	during hospitalization for the index event
Secondary	Left ventricular thrombus formation		5 ± 2 days, 4 months, 12 months post PCI
Secondary	Biomarker concentrations of myocardial necrosis (enzymatic infarct size; high-sensitivity troponin T)		at baseline, 4 months, 12 months post PCI
Secondary	Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide)		at baseline, 4 months, 12 months post PCI
Secondary	Renal function (eGFR)	as measured by the MDRD and CKD-EPI formula	during hospitalization for the index event
Secondary	Renal function (Cystatin C-based calculation of creatinine clearance)		during hospitalization for the index event
Secondary	Cardiac autonomic function: Deceleration capacity of heart rate		5 ± 2 days, 4 months, 12 months post PCI
Secondary	Cardiac autonomic function: Heart rate variability		5 ± 2 days, 4 months, 12 months post PCI
Secondary	Cardiac autonomic function: Periodic repolarization dynamics		5 ± 2 days, 4 months, 12 months post PCI
Secondary	Cardiac autonomic function: Baroreflex sensitivity		5 ± 2 days, 4 months, 12 months post PCI
Secondary	Cardiac autonomic function: Skin sympathetic nerve activity		5 ± 2 days, 4 months, 12 months post PCI