Sequential Treatment of Extra-Corporeal Shock Wave Combined With aUtologous Bone marRow Mesenchymal Stem Cells on Patients With ischEmic Heart Disease : the S-CURE Study

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy, safety and tolerability of autologous bone marrow derived mesenchymal stem cells compared to placebo (sham operation) when administered via percutaneous coronary infusion to patients with ischemic heart disease, who are screened by D-SPECT and have pretreated with 3-month cardiac shock wave therapy.

Official Title
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Sequential Treatment of Extra-Corporeal Shock Wave Combined With aUtologous Bone marRow Mesenchymal Stem Cells in Patients With ischEmic Heart Disease : the S-CURE Study

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Combination Product: CSWT+BMMSCs
* Device: CSWT+Sham operation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females; Chronic ischemic heart failure, previous anterior myocardial infarction > 3months; Viable myocardium is detected by D-SPECT; LVEF < 50% measured by echocardiography or NYHA II-IV; No planed reasonable revascularization procedures; At least 30 days standard medical therapy for heart failure before screening; Worsening heart failure within 6 months or have a NT-proBNP ≥1000 pg/mL or BNP ≥200 pg/mL within 30 days of screening (including screening); or have a 6-minute walk test (6MWT) distance of ≤425 meters at screening; Written informed consent. Exclusion Criteria: Ventricular thrombus; Myocardial infarction, TIA or stroke < 3 months; CRT/CRT-D implantation, heart transplantation, cardiomyoplasty, left ventricular reduction surgery, heart failure-related device interventions, or cardiac shunt implantation; Active infection or fever; Chronic inflammatory disease; HIV infection or active hepatitis; Hemoglobin A1c (HbA1c) ≥ 9% at screening; Body mass index (BMI) ≥ 40 kg/m2 at screening; Chronic kidney disease (CKD) requiring dialysis (Stage 5) or estimated creatinine clearance < 30 mL/min/1.73㎡ at screening; Allergies to any equine, porcine, or bovine products; Abnormal laboratory values at screening：Platelets < 50,000 μL;Hemoglobin < 9.0 g/dL; Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 times the upper limit of normal (ULN); Pregnancy; Mental retardation; Participation in other clinical study < 1 month.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: S-CURE study has a two-stage design. Stage 1 is an open-labled, lead-in study. 20 participants will be enrolled in this stage. It is conducted to assess the feasibility and safety of the study procedures as well as the bioactivity of the products. Stage 2 is an randomized, placebo controlled study, 100 participants will be enrolled in this stage.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSWT+BMMSCs<br>Patients in CSWT+BMMSCs group will receive a 3-month cardiac shock wave therapy and then a total of 1 million/kg BMMSCs will be infused using the stop-flow technique through an over-the-wire balloon catheter positioned in a coronary artery or bypass graft supplying the targeting viable myocardium. | Combination Product: CSWT+BMMSCs<br>* All participants will screened by D-SPECT to assess the myocardium viability. If the viable myocardium is detected, Patients will be randomized to receive cardiac shock wave therapy with an equipment (Modulith SLC; Storz Medical, Switzerland) followed the recommended protocol developed by Tohoku University of Japan and the protocol developed by the University of Essen, Germany. An over-the-wire catheter will be positioned in the target coronary artery and the cells resuspended in saline will be injected intracoronary.<br>|
| Sham Comparator: CSWT+Sham operation<br>Placebo group will receive a 3-month CSWT and a sham procedure. | Device: CSWT+Sham operation<br>* Patients randomized to this group will receive a routine cardiac shock wave therapy and coronary angiography. No cells will be administered via the coronary artery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 6 months follow-up in LVEF. | The primary outcome will evaluate the change in left ventricular function as measured by echocardiography and D-SPECT for left ventricular ejection fraction (LVEF). | 6 months | 
| Change from baseline to 6 months follow-up in infarct size. | The primary outcome will evaluate the change in infarct size as measured by D-SPECT. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 6 months follow-up in exercise distance increment | A secondary objective will be the changes from baseline to 6 months post-treatment in the distance walked as measured by the 6-minute walk test. | 6 months | 
| Change from baseline to 6 months follow-up in quality of life measured by MLHFQ | A secondary objective will be the change in quality of life in patients treated with bone marrow derived mesenchymal stem cells compared to placebo using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). | 6 months | 
| Change from baseline to 6 months follow-up in NYHA Classification. | A secondary objective will be the change from baseline to Month 6 in NYHA Classification in patients treated with BMMSCs compared to placebo. | 6 months | 
| Percent of patients with adverse events. | A secondary objective will be the overall safety and tolerability of BMMSCs versus placebo in patients with ICM from time of cell-infusion through 6 months post-treatment follow-up by the percentage of patients with adverse events. | 6 months | 
| Change from baseline to 6 months follow-up in exercise time increment. | A secondary objective will be the changes from baseline to 6 months post-treatment in the exercise time as measured by the cardiopulmonary exercise test. | 6 months | 
| Change from baseline to 6 months follow-up in quality of life measured by KCCQ | A secondary objective will be the change in quality of life in patients treated with bone marrow derived mesenchymal stem cells compared to placebo using the Kansas City Cardiomyopathy Questionnaire (KCCQ). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cells, ischemic heart disease.