A First-in-Human Study to Evaluate the Safety and Efficacy of Left Ventricular Assist Device Combined With Exosome Therapy for Patients With Heart Failure（RESTORATION）

Korábbi kezelés

• Planned biventricular assist device (Bi-VAD) support prior to LVAD implantation.
• Untreated abdominal aortic aneurysm (AAA) diagnosed within 6 months prior to enrollment with diameter>5 cm.
• History of severe hypersensitivity to the investigational product (exosome formulation) or excipients.
• Participation in another interventional clinical trial (device/cell/biological product) within 30 days prior to enrollment.

Más betegség

• Heart failure caused by thyroid disease, hypertrophic obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy.
• History of any solid organ transplantation (including heart transplantation).
• Irreversible severe right heart failure that cannot be corrected by medications or right ventricular assist device.
• Pre-existing technical barriers at the time of LVAD implantation conferring an abnormally high surgical risk as judged by the heart team.
• Inability to tolerate anticoagulation, antiplatelet therapy, or any other perioperative/postoperative treatment required by the investigator based on the subject's condition.
• Active uncontrolled systemic infection, including but not limited to sepsis, active infective endocarditis, and LVAD-related pump infection.
• Confirmed malignancy with estimated survival less than 1 year.
• Presence of psychiatric disorders, irreversible cognitive impairment or psychosocial problems that may impair protocol compliance and left ventricular assist system (LVAS) management.
• Any other condition judged by the investigator to render the subject unsuitable for participation in this study.

Laborértékek

• Presence of any risk factor indicating severe end-organ dysfunction or failure:
  • INR ≥2.0 not attributable to anticoagulation therapy
  • Total bilirubin>43 μmol/L (2.5 mg/dL), shock liver, or biopsy-proven liver cirrhosis
  • History of severe chronic obstructive pulmonary disease (COPD): FEV1/FVC<0.7 and FEV1<50% of predicted value
  • Fixed pulmonary hypertension with latest pulmonary vascular resistance (PVR) ≥8 Wood units and no response to pharmacotherapy
  • History of stroke within 90 days prior to enrollment; or cerebrovascular disease with severe (>80%) uncorrected carotid artery stenosis
  • Serum creatinine ≥221 μmol/L (2.5 mg/dL) or requirement for chronic renal replacement therapy
  • Severe peripheral vascular disease (PVD) with rest pain or limb ulceration
• Abnormal nutritional status: If only one test result is available, prealbumin<150 mg/L (15 mg/dL) OR albumin<30 g/L (3 g/dL); if both results are available, prealbumin<150 mg/L (15 mg/dL) AND albumin<30 g/L (3 g/L).
• Platelet count <100×10⁹/L (100,000/μL).

Egyéb

• Moderate to severe aortic regurgitation that was not corrected concomitantly at the time of LVAD implantation.
• Presence of an aortic mechanical valve that was not replaced with a bioprosthesis or sutured closed during LVAD implantation.
• Known hypocoagulable or hypercoagulable state, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia.
• Receipt of mechanical circulatory support other than intra-aortic balloon pump (IABP) at enrollment.
• Female subjects who are pregnant or breastfeeding; positive pregnancy test at screening for women of childbearing potential.

• Subject or legal representative has signed the Informed Consent Form (ICF).
• Age ≥ 18 years.
• Body Surface Area (BSA) ≥ 1.2 m².
• NYHA Class III B or NYHA Class IV.
• Left ventricular ejection fraction (LVEF) ≤ 25%.
• a) Inotrope-dependent; OR b) Cardiac Index (CI) < 2.2 L/min/m² in the absence of inotropes, and the subject must also meet one of the following:
  • Receiving optimal medical management per current heart failure guidelines for at least 45 days out of the preceding 60 days, with evidence of treatment failure;
  • Advanced heart failure for at least 14 days AND dependent on intra-aortic balloon pump (IABP) support for at least 7 days.
• Females of childbearing potential must agree to use adequate contraception throughout the study.