Clinical trial NCT04939805: CRP Apheresis in STEMI
Official title: Selective C-reactive Protein Apheresis in ST-elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ST Elevation Myocardial Infarction
C-Reactive Protein
Apheresis
Myocardial Injury
Keywords: Cardiac magnetic resonance imaging
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2021-06-25
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Primary efficacy endpoint
timeFrame: 5 ± 2 days post PCI
Secondary outcomes:
measure: Safety endpoint
timeFrame: during hospitalization for the index event
measure: All-cause mortality or hospitalization for heart failure within 12 months after randomization
timeFrame: within 12 months after randomization
measure: CMR endpoints defined as: Left ventricular ejection fraction and microvascular obstruction and exploratory (intramyocardial hemorrhage, edema extent, myocardial salvage, native T1 mapping, strain)
timeFrame: at baseline, 4 months and 12 months after PCI for STEMI
measure: Hospitalization for heart failure within 12 months after randomization
timeFrame: within 12 months after randomization
measure: Cardiovascular mortality at 12 months
timeFrame: within 12 months after randomization
measure: CRP concentrations
timeFrame: during hospitalization for the index event
measure: Left ventricular thrombus formation
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
measure: Biomarker concentrations of myocardial necrosis (enzymatic infarct size; high-sensitivity troponin T)
timeFrame: at baseline, 4 months, 12 months post PCI
measure: Biomarker concentrations of hemodynamic stress (N-terminal pro-B-Type Natriuretic Peptide)
timeFrame: at baseline, 4 months, 12 months post PCI
measure: Renal function (eGFR)
timeFrame: during hospitalization for the index event
measure: Renal function (Cystatin C-based calculation of creatinine clearance)
timeFrame: during hospitalization for the index event
measure: Cardiac autonomic function: Deceleration capacity of heart rate
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
measure: Cardiac autonomic function: Heart rate variability
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
measure: Cardiac autonomic function: Periodic repolarization dynamics
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
measure: Cardiac autonomic function: Baroreflex sensitivity
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
measure: Cardiac autonomic function: Skin sympathetic nerve activity
timeFrame: 5 ± 2 days, 4 months, 12 months post PCI
Other outcomes:
Locations:
city: Graz
country: Austria
facility: University Clinic for Cardiology and Nephrology, Medical University of Graz
city: Innsbruck
country: Austria
facility: University Clinic of Internal Medicine III, Cardiology and Angiology. University Clinic of Internal Medicine IV, Nephrology and Hypertensiology. University Clinic of Radiology.
city: Salzburg
country: Austria
facility: University Clinic of Internal Medicine II, Paracelsus Medical University Salzburg
city: Lübeck
country: Germany
facility: Medical Clinic II - University Heart Center Lübeck
state: Schleswig-Holstein
city: Leipzig
country: Germany
facility: Leipzig Heart Center
Study officials:
affiliation: University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck
name: Sebastian J Reinstadler, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: