Ischemic Heart Disease
Conditions
Keywords
stem cells, ischemic heart disease.
Brief summary
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.
Interventions
COMBINATION_PRODUCTCSWT+BMMSCs
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.
DEVICECSWT+Sham operation
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.
Sponsors
Shanghai 10th People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and non-pregnant, non-lactating females; 2. Chronic ischemic heart failure, previous anterior myocardial infarction \> 3months; 3. Viable myocardium is detected by D-SPECT; 4. LVEF \< 50% measured by echocardiography or NYHA II-IV; 5. No planed reasonable revascularization procedures; 6. At least 30 days standard medical therapy for heart failure before screening; 7. 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; 8. Written informed consent.
Exclusion criteria
1. Ventricular thrombus; 2. Myocardial infarction, TIA or stroke \< 3 months; 3. CRT/CRT-D implantation, heart transplantation, cardiomyoplasty, left ventricular reduction surgery, heart failure-related device interventions, or cardiac shunt implantation; 4. Active infection or fever; 5. Chronic inflammatory disease; 6. HIV infection or active hepatitis; 7. Hemoglobin A1c (HbA1c) ≥ 9% at screening; 8. Body mass index (BMI) ≥ 40 kg/m2 at screening; 9. Chronic kidney disease (CKD) requiring dialysis (Stage 5) or estimated creatinine clearance \< 30 mL/min/1.73㎡ at screening; 10. Allergies to any equine, porcine, or bovine products; 11. 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); 12. Pregnancy; 13. Mental retardation; 14. Participation in other clinical study \< 1 month.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to 6 months follow-up in infarct size. | 6 months | The primary outcome will evaluate the change in infarct size as measured by D-SPECT. |
| Change from baseline to 6 months follow-up in LVEF. | 6 months | The primary outcome will evaluate the change in left ventricular function as measured by echocardiography and D-SPECT for left ventricular ejection fraction (LVEF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to 6 months follow-up in NYHA Classification. | 6 months | A secondary objective will be the change from baseline to Month 6 in NYHA Classification in patients treated with BMMSCs compared to placebo. |
| Percent of patients with adverse events. | 6 months | 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. |
| Change from baseline to 6 months follow-up in exercise time increment. | 6 months | 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. |
| Change from baseline to 6 months follow-up in exercise distance increment | 6 months | 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. |
| Change from baseline to 6 months follow-up in quality of life measured by KCCQ | 6 months | 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). |
| Change from baseline to 6 months follow-up in quality of life measured by MLHFQ | 6 months | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Average number of clinical events over 12 months post-treatment | 12 months | A secondary outcome will assess the efficacy of BMMSc compared to placebo on the average number of events per patient over 12 months post-treatment in each treatment arm (total number events in each arm/total number of patients in each arm). The events include: all-cause deaths, cardiovascular hospitalizations, and unplanned outpatient or emergency department visits to treat acute decompensated heart failure. The clinical events used in this endpoint will be adjudicated by an independent clinical endpoint committee who are blinded to treatment. |
| Percent of patients with major adverse cardiac events (MACE) | 6 months | A secondary objective will be the overall safety and tolerability of BMMSCs versus placebo in patients with ICM by the percentage of patients who experience MACE events. MACE events include: unstable angina requiring hospitalization, myocardial infarction, stroke, worsening heart failure requiring hospitalization, VAD implantation, heart transplant, resuscitated sudden death, and cardiovascular death. |
Countries
China
Contacts
Primary ContactYuxi Sun
Backup ContactDachun Xu, MD,PhD
Outcome results
None listed