Acute Myocardial Infarction (AMI), Cardiogenic Shock
Conditions
Keywords
C-reactive protein, CRP apheresis, Selective CRP apheresis, Inflammation, Infarct-related cardiogenic shock, Acute myocardial infarction, CLIP score, PentraSorb-CRP, Pilot study, Multicenter study
Brief summary
Cardiogenic shock complicating acute myocardial infarction remains associated with high short-term mortality despite guideline-directed therapy. Systemic inflammation, particularly elevated C-reactive protein (CRP), may contribute to ongoing myocardial injury and organ dysfunction. The CRP-SHOCK trial is an investigator-initiated, prospective, randomized, open-label, multicenter pilot study evaluating selective CRP apheresis as an adjunct to standard of care in patients with infarct-related cardiogenic shock. Patients are randomized to receive either standard therapy alone or standard therapy plus selective CRP apheresis using the PentraSorb®-CRP system. The primary objective is to assess the effect of CRP apheresis on the CLIP score at 66 ± 8 hours after randomization. Secondary objectives include clinical outcomes, inflammatory biomarkers, and safety endpoints.
Detailed description
Cardiogenic shock following acute myocardial infarction is associated with a high inflammatory response and mortality rates of approximately 40-50% despite early revascularization and intensive care treatment. Experimental and clinical evidence suggests that elevated C-reactive protein (CRP) contributes to myocardial injury, impaired tissue regeneration, and adverse outcomes. The CRP-SHOCK trial investigates whether selective removal of circulating CRP by apheresis improves short-term risk stratification and clinical outcomes in patients with infarct-related cardiogenic shock. The intervention consists of up to three CRP apheresis sessions initiated within 5 ± 1 hours after randomization and repeated at predefined intervals using the PentraSorb®-CRP system. The primary efficacy endpoint is the CLIP score at 66 ± 8 hours after randomization. Secondary endpoints include mortality, major adverse cardiovascular events, biomarkers of inflammation and organ function, and safety outcomes such as bleeding, stroke, and infections. The trial is conducted as a multicenter pilot study in Germany and Austria.
Interventions
DEVICESelective C-reactive protein apheresis (PentraSorb®-CRP)
Selective removal of circulating C-reactive protein using the PentraSorb®-CRP adsorber system as an adjunct to guideline-directed standard of care.
OTHERStandard of care
Guideline-directed medical and interventional treatment for cardiogenic shock complicating acute myocardial infarction.
Sponsors
Leipzig Heart Science gGmbH
Helios Health Institute GmbH
Heart Center Leipzig at University of Leipzig
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized in a 1:1 ratio to receive either standard of care alone or standard of care plus selective C-reactive protein (CRP) apheresis. Randomization is performed centrally using a computerized system. Participants remain in their assigned treatment group throughout the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Cardiogenic shock complicating acute myocardial infarction with planned revascularization by percutaneous coronary intervention (PCI). * Cardiogenic shock defined as: * Systolic blood pressure \<90 mmHg for \>30 minutes or requirement of catecholamine infusion to maintain systolic blood pressure ≥90 mmHg, and * Signs of impaired organ perfusion (at least one of the following): Cold, clammy skin and extremities, Altered mental status, Oliguria with urine output \<30 mL/hour, Arterial lactate \>2 mmol/L * C-reactive protein (CRP) level ≥7 mg/L at baseline. * Age ≥18 years. * Informed consent provided by the participant or, if the participant is unable to consent, inclusion after assessment and documentation of the presumed patient's will by two physicians (one independent), with informed consent obtained as soon as possible.
Exclusion criteria
* Fever (body temperature \>38°C) or acute infection with fever within the last 14 days. * Chronic inflammatory disease. * Known history of severe hepatic failure. * Chronic kidney disease with creatinine clearance \<30 mL/min/1.73 m² prior to hospital admission. * Life expectancy \<12 months prior to cardiogenic shock. * Participation in another interventional clinical trial. * Pregnancy. * Resuscitation duration \>30 minutes. * Cardiogenic shock due to causes other than acute myocardial infarction. * Onset of cardiogenic shock \>12 hours before randomization. * Age \>80 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CLIP score | 66 ± 8 hours after randomization | The CLIP score (Cystatin C, Lactate, Interleukin-6 and N-terminal pro B-type natriuretic peptide \[NT-proBNP\] score) is a biomarker-based risk score for predicting 30-day mortality in cardiogenic shock complicating acute myocardial infarction. It is calculated via a logistic regression model using the four biomarkers (Cystatin C, Lactate, Interleukin-6, and NT-proBNP), yielding a probability score ranging from 0 to 1 (or 0% to 100% when multiplied by 100). Higher scores indicate a higher probability of 30-day mortality, i.e., a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular events (MACE) | 30 days | Composite endpoint of cardiovascular death, non-fatal myocardial infarction, or re-admission for heart failure. |
| All-cause mortality | 30 days | Death from any cause within 30 days after randomization. |
| Cardiovascular mortality | 30 days | Death due to cardiovascular causes within 30 days after randomization. |
| CLIP score over time | 18 ± 4 hours, 42 ± 6 hours, and 66 ± 8 hours after randomization | The CLIP score (Cystatin C, Lactate, Interleukin-6 and N-terminal pro B-type natriuretic peptide \[NT-proBNP\] score) is a biomarker-based risk score for predicting 30-day mortality in cardiogenic shock complicating acute myocardial infarction. It is calculated via a logistic regression model using the four biomarkers (Cystatin C, Lactate, Interleukin-6, and NT-proBNP), yielding a probability score ranging from 0 to 1 (or 0% to 100% when multiplied by 100). Higher scores indicate a higher probability of 30-day mortality, i.e., a worse outcome. |
| Individual components of the CLIP score | 18 ± 4 hours, 42 ± 6 hours, and 66 ± 8 hours after randomization | The CLIP score (Cystatin C, Lactate, Interleukin-6 and N-terminal pro B-type natriuretic peptide \[NT-proBNP\] score) is a biomarker-based risk score for predicting 30-day mortality in cardiogenic shock complicating acute myocardial infarction. It is calculated via a logistic regression model using the four biomarkers (Cystatin C, Lactate, Interleukin-6, and NT-proBNP), yielding a probability score ranging from 0 to 1 (or 0% to 100% when multiplied by 100). Higher scores indicate a higher probability of 30-day mortality, i.e., a worse outcome. |
| C-reactive protein (CRP) concentration | 9 ± 1 hours, 34 ± 4 hours, 58 ± 6 hours, and 66 ± 8 hours after randomization | Serum CRP concentrations measured before and after CRP apheresis sessions. |
| Peak NT-proBNP concentration | During index hospitalization | Maximum NT-proBNP serum concentration recorded during the index hospital stay. |
| Peak serum creatinine concentration | During index hospitalization | Maximum serum creatinine concentration recorded during the index hospital stay. |
| Cardiac power index | 18 ± 4 hours, 42 ± 6 hours, and 66 ± 8 hours after randomization | The Cardiac Power Index (CPI) is a continuous hemodynamic measurement reflecting the rate of cardiac energy output indexed to body surface area, calculated as cardiac index × mean arterial pressure × a constant (W/m²). It is not a score on a defined scale but a continuous physiological parameter without fixed minimum or maximum values. Normal values are generally reported in the range of 0.5-0.7 W/m². Lower CPI values are associated with worse outcomes, including higher mortality, need for cardiac transplantation, or ventricular assist device placement - thus, higher values indicate better cardiac performance. |
| Time to hemodynamic stabilization | hospital discharge | Time from randomization to sustained hemodynamic stabilization as defined by the treating physician. |
| Duration of catecholamine therapy | hospital discharge | Total duration of vasopressor and inotropic support. |
| Length of intensive care unit stay | hospital discharge | Number of days spent in the intensive care unit. |
| Length of hospital stay | hospital discharge | Total length of hospital stay in days. |
Countries
Germany
Contacts
CONTACTCRP-SHOCK Leipzig Heart Science gGmbH
PRINCIPAL_INVESTIGATORProf. Dr. med. Holger Thiele Thiele
Heart Center Leipzig at University of Leipzig
Outcome results
None listed