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

Phase 1

• Conditions: Ischemic Heart Disease
• Interventions: Device: CSWT+Sham operation; Combination Product: CSWT+BMMSCs

• Registration Number: NCT03397095
• Lead Sponsor: Shanghai 10th People's Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-12-28
• Study First Submitted QC: 2018-01-05
• Study First Posted: 2018-01-11
• Study Start: 2018-04-03
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-23
• Last Update Posted: 2019-08-28
• Primary Completion: 2019-12-01
• Study Completion: 2022-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSWT+Sham operation	CSWT+Sham operation	Placebo group will receive a 3-month CSWT and a sham procedure.
CSWT+BMMSCs	CSWT+BMMSCs	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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).
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.
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 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).

Trial Locations

Locations (1)

Shanghai Tenth People's Hospital, Tongji University; 🇨🇳 Shanghai, Shanghai, China