hiPSC-CMs-loaded Chitosan Patch to Treat Severe Chronic Ischemic Heart Disease

Официальное название

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Human Induce Pluripotent Stem Cell-derived Cardiomyocytes(HiCM-188) -Loaded Chitosan Patch to Treat Severe Chronic Ischemic Heart Disease

Обзор

This is an exploratory study. A total of 16 patients meeting the inclusion and exclusion criteria and awaiting coronary artery bypass grafting (CABG) surgery will be enrolled. After providing informed consent, participants will be randomized 1:1 under double-blind conditions into two groups: 1. CABG + HiCM-188-loaded chitosan patch group (patch size: 2×4 cm; containing 5 million cells per patch) 2. CABG + blank chitosan patch group (identical in appearance but without HiCM-188 cells). During CABG surgery, investigators will apply two HiCM-188-loaded chitosan patches onto the epicardial surface over regions of hypokinetic myocardium. The total transplanted cell dose per patient in the treatment group is 1 × 10⁷ . In the control group, eight patients will undergo identical surgical procedures with application of chitosan patches without HiCM-188 cells.

Вмешательства

• Препарат HiCM-188 Chitosan Patch
  Patients receive standard coronary artery bypass grafting (CABG) surgery plus epicardial application of two chitosan patches (each 2×4 cm in size, loaded with 5 million HiCM-188 cells), delivering a total dose of 1 × 10⁷ cardiomyocytes.
• Препарат Blank Chitosan Patch
  Patients receive standard CABG surgery plus epicardial application of two identical-appearing chitosan patches containing no HiCM-188 cells

Первичные конечные точки

• Proportion and frequency of patients experiencing sustained ventricular tachycardia lasting more than 30 seconds [Срок оценки: 1~6 Month Post-operation]
• Incidence of allogeneic human-derived tumor formation [Срок оценки: Baseline, 1, 3, 6 months post-operation]

Вторичные конечные точки (11)

• Change in infarct size [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in regional left ventricular function [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in regional left ventricular wall thickness [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in left ventricular end-diastolic wall thickness [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in left ventricular ejection fraction (LVEF) [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in left ventricular end-diastolic volume (LVEDV) [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in left ventricular end-systolic volume (LVESV) [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Change in regional myocardial perfusion [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Six-minute walk test [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• New York Heart Association (NYHA) functional classification [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]
• Minnesota Living with Heart Failure Questionnaire (MLHFQ) score [Срок оценки: Baseline, 1, 3, 6, and 12 months post-operation]

Критерии участия

Критерии включения

• Age between 18 and 80 years (inclusive).
• Willingness and ability to give written informed consent.
• Chronic left ventricular dysfunction classified as Stage D (refractory end-stage heart failure) according to ACC staging criteria.
• NYHA functional class III-IV despite optimized guideline-directed medical therapy for heart failure.
• Indication for coronary artery bypass grafting (CABG), meeting one of the following anatomical criteria:

5.1 Class I Indications :

• Left ventricular dysfunction with significant left main coronary artery disease;
• Left ventricular dysfunction with "left main equivalent" disease (i.e., ≥70% stenosis in proximal LAD or proximal LCx);
• Left ventricular dysfunction with two- or three-vessel disease including proximal LAD stenosis.

5.2 Class IIa Indication : Left ventricular dysfunction with substantial viable, akinetic but revascularizable myocardium, not covered by above Class I anatomical criteria.

• Left ventricular ejection fraction (LVEF) ≤40% as measured by echocardiography or cardiac MRI within 6 months prior to enrollment (excluding measurements obtained within 1 month post-myocardial infarction).
• Echocardiographic evidence of regional wall motion abnormalities (hypokinesis, akinesis, or presence of ventricular aneurysm).

Критерии исключения

Patients meeting any of the following criteria are ineligible for study participation:

• History of permanent pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy (CRT) device implantation.
• Severe valvular heart disease or prior prosthetic valve replacement.
• Prior percutaneous coronary intervention (PCI) with stent implantation.
• Chronic atrial fibrillation.
• History of sustained ventricular tachycardia or aborted sudden cardiac death.
• Baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m².
• Hematocrit <25%.
• Severe contrast media allergy (anaphylactic or life-threatening reaction history).
• Coagulation disorder (INR >1.5 without therapeutic anticoagulation, platelets <50×10⁹/L, or clinically significant bleeding diathesis).
• Known hypersensitivity to penicillin or streptomycin.
• Contraindication to undergoing cardiac MRI (e.g., incompatible implanted devices, severe claustrophobia unresponsive to premedication).
• History of solid organ or bone marrow transplantation.
• Active malignancy or history of cancer within the past 5 years (except non-melanoma skin cancer or carcinoma in situ).
• Life expectancy <1 year due to non-cardiac conditions.
• Long-term systemic immunosuppressive therapy (e.g., corticosteroids, TNF-α inhibitors).
• Contraindications to immunosuppressive therapy (e.g., active infection, uncontrolled diabetes, peptic ulcer disease).
• Active infectious diseases: HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis (Treponema pallidum, TP).
• Currently participating in another interventional clinical trial.
• Pregnant or lactating women.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Second Xiangya Hospital of Central South University — Чанша

Идентификаторы

NCT: NCT07471698 · LXB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗