Safety and Efficacy of FAP iCDC in Acute Myocardial Infarction With Cardiogenic Shock

Phase 1Not Yet RecruitingNCT07380659

Second Affiliated Hospital, School of Medicine, Zhejiang University18 enrolled

Overview

To study the safety and efficacy of fibroblast activation protein (FAP)-targeted allogeneic immunosuppressive chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of acute myocardial infarction with cardiogenic shock and provide a new method for the treatment of acute myocardial infarction with cardiogenic shock.

Background: Cardiogenic shock following acute myocardial infarction (AMI) remains a major unresolved clinical challenge. Despite advances in urgent revascularization and mechanical circulatory support, short-term mortality remains unacceptably high, approaching 40% within 30 days. Few evidence-based therapies have demonstrated a meaningful survival benefit, highlighting the urgent need for novel, mechanism-driven interventions. Growing clinical and experimental evidence indicates that a dysregulated systemic inflammatory response-manifested by hyperthermia, leukocytosis, and elevated proinflammatory mediators-plays a central role in the pathophysiology and progression of cardiogenic shock. Excessive inflammation exacerbates myocardial dysfunction, promotes multiorgan injury, and impairs recovery, suggesting that targeted immunomodulation may represent a complementary therapeutic strategy in this high-risk population. Dendritic cells (DCs), as professional antigen-presenting cells, occupy a pivotal position at the interface of innate and adaptive immunity and are uniquely suited to orchestrate context-dependent immune responses. In particular, tolerogenic DCs exert potent immunosuppressive effects through regulatory cytokine production, expression of co-inhibitory ligands, antigen-specific suppression of effector T cells, and induction of regulatory T cells. Collectively, these properties render DCs an attractive yet underexplored cellular platform for resolving excessive inflammation and promoting tissue repair in cardiogenic shock with AMI. Purpose: In this prospective clinical study, the investigators engineered a stable, immunosuppressive, and fibrotic lesion-targeted DC therapy, termed immunosuppressive DCs (iCDC). This study was designed to evaluate the safety and preliminary efficacy of allogeneic fibroblast activation protein (FAP)-targeted iCDC therapy in patients with AMI complicated by cardiogenic shock. Study design: This single-center, prospective, concurrent non-randomized controlled clinical trial enrolls patients aged 18-80 years presenting with acute myocardial infarction complicated by cardiogenic shock. Eligible patients are treated with allogeneic FAP-targeted immunosuppressive iCDC therapy. Outcome measure: The primary outcome is the safety of FAP-targeted immunosuppressive iCDC therapy in patients with AMI complicated by cardiogenic shock. Secondary outcomes include 30-day all-cause mortality; hemodynamic parameters following iCDC therapy (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate); time to hemodynamic stabilization; dose and duration of vasopressor and inotropic support; arterial lactate levels; changes in biomarkers (BNP, CRP, creatinine, ALT, AST, and inflammatory mediators); need for and duration of mechanical ventilation; need for and duration of left ventricular assist device implantation; intensive care unit and total hospital length of stay; left ventricular ejection fraction assessed by echocardiography; SAPS II score; SCAI shock classification; heart failure symptom burden assessed by NYHA functional class and the Kansas City Cardiomyopathy Questionnaire; incidence of major adverse cardiovascular events (MACE), including cardiac death and heart failure hospitalization; and incidence of adverse events.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria（patients）: * Age ≥ 18 years and \< 80 years. * Acute ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock, meeting all the following conditions: 1. Post-emergent revascularization (PCI or CABG) 2. Systolic blood pressure \< 90 mmHg for \>30 minutes, or requiring catecholamine support to maintain systolic blood pressure \>90 mmHg 3. Signs of impaired organ perfusion, meeting at least one of the following criteria: 1. Altered mental status 2. Cold, clammy skin and extremities 3. Oliguria, with urine output \<30 mL/h 4. Arterial lactate level \>2 mmol/L * The patient or their legally authorized representative is capable of providing verbal confirmation of understanding the trial risks, benefits, and treatment alternatives associated with receiving immunosuppressive CAR-DC therapy, and provides written informed consent prior to participation in this clinical trial. Exclusion Criteria（patients）: 1. Acute mechanical complications of infarction (e.g., ventricular septal rupture, acute mitral regurgitation). 2. Cardiac arrest. 3. Hypoxic-ischemic brain injury (cerebral injury with fixed and dilated pupils not attributable to medication). 4. Shock due to other causes (e.g., sepsis, hypovolemia). 5. Resuscitation duration \>30 minutes. 6. Absence of spontaneous cardiac activity. 7. Persistent electrical instability. 8. Active bleeding or contraindications to heparin use. 9. Active autoimmune disease requiring immunosuppressive therapy. 10. History of malignancy. 11. Infection, including: * Active hepatitis B (HBV DNA \>1000 copies/mL by PCR), hepatitis C, syphilis, or HIV infection at screening. * Uncontrolled systemic fungal, bacterial, viral, or other pathogen infections. 12. Pregnant women. 13. Contraindications to the investigational drug or study procedures. Inclusion Criteria（donors）: * Age ≥ 18 years and ≤ 75 years. * Has provided written informed consent. * Hematocrit \>30%, lymphocyte count \>0.5 × 10\^9/L, platelet count \>60 × 10\^9/L. * Pathogen screening results must be negative for HIV (antigen, core antibody, and RNA), HBV (surface antigen and core antibody), HCV, syphilis, CMV, and EBV. Exclusion Criteria（donors）: * Active infection requiring treatment. * History of malignancy. * Active autoimmune disease requiring immunosuppressive therapy.

Outcomes

Primary Outcomes

The proportion of subjects with Dose-limiting toxicity (DLT)

The proportion of participants with DLT as assessed by CTCAE v5.0

Time frame: in 14 days after injection

Incidence of treatment-emergent adverse events (TEAEs)

Incidence of iCDC treatment-emergent adverse events

Time frame: in 14 days after injection

Secondary Outcomes

All-cause mortality

All-cause mortality at 30 days after iCDC treatment

Time frame: 30 days after injection

Systolic blood pressure

Systolic blood pressure (mmHg) measured using a calibrated sphygmomanometer under standardized conditions.

Time frame: 24 hours、48 hours、72 hours、7 days after injection

Diastolic blood pressure

Diastolic blood pressure (mmHg) measured using a calibrated sphygmomanometer under standardized conditions.

Time frame: 24 hours、48 hours、72 hours、7 days after injection

Mean arterial pressure

The mean arterial pressure (MAP) is calculated using the following formula: MAP=DBP+1/3(SBP-DBP)；DBP : Diastolic blood pressure，SBP ：Systolic blood pressure

Time frame: 24 hours、48 hours、72 hours、7 days after injection

Time to hemodynamic stability

Sustained (\> 60 min) systolic blood pressure \>90 mmHg without requirement for catecholamines and without signs of peripheral endorgan hypoperfusion

Time frame: From the end of the iCDC infusion to achievement of hemodynamic stability, assessed continuously until ICU discharge (up to 30 days).

Dose of vasopressors

Dose of vasopressors administered to the participant.

Time frame: 24 hours、48 hours、72 hours、7 days after injection

Duration of vasopressor use

Duration of vasopressor therapy in days treated with vasopressor between enrollment and hospital discharge. A day treated with vasopressor is any day during the hospital period where the patient received a vasopressor.

Time frame: From enrollment to hospital discharge (up to 30 days).

Dose of inotropic drugs

Dose of inotropic drugs administered to the participant.

Time frame: 24 hours、48 hours、72 hours、7 days after injection

Duration of inotropic drugs use

Duration of inotropic drugs therapy in days treated with inotropic drugs between enrollment and hospital discharge. A day treated with inotropic drugs is any day during the hospital period where the patient received inotropic drugs

Time frame: From enrollment to hospital discharge (up to 30 days).

Serum lactate level

Lactate is assessed via arterial blood gas analysis.

Time frame: The measurement frequency is once every 8 hours for a duration of 48 hours.

Change in B-type natriuretic peptide (BNP) level from baseline

Change in serum B-type natriuretic peptide concentration compared with baseline.

Time frame: 7 days，14 days，30 days after injection.

Change in C-reactive protein (CRP) level from baseline

Change in serum C-reactive protein concentration compared with baseline.