Clinical trial NCT03397095: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Ischemic Heart Disease
Keywords: stem cells, ischemic heart disease.
Lead sponsor: Shanghai 10th People's Hospital
Sponsor class: OTHER
First posted: 2018-01-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline to 6 months follow-up in LVEF.
timeFrame: 6 months
measure: Change from baseline to 6 months follow-up in infarct size.
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline to 6 months follow-up in exercise distance increment
timeFrame: 6 months
measure: Change from baseline to 6 months follow-up in quality of life measured by MLHFQ
timeFrame: 6 months
measure: Change from baseline to 6 months follow-up in NYHA Classification.
timeFrame: 6 months
measure: Percent of patients with adverse events.
timeFrame: 6 months
measure: Change from baseline to 6 months follow-up in exercise time increment.
timeFrame: 6 months
measure: Change from baseline to 6 months follow-up in quality of life measured by KCCQ
timeFrame: 6 months
Other outcomes:
measure: Percent of patients with major adverse cardiac events (MACE)
timeFrame: 6 months
measure: Average number of clinical events over 12 months post-treatment
timeFrame: 12 months
Locations:
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital, Tongji University
state: Shanghai
Study officials:
affiliation: Shanghai 10th People's Hospital
name: Yawei Xu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM; REPAIR-AMI Investigators. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1210-21. doi: 10.1056/NEJMoa060186.
citation: Assmus B, Walter DH, Seeger FH, Leistner DM, Steiner J, Ziegler I, Lutz A, Khaled W, Klotsche J, Tonn T, Dimmeler S, Zeiher AM. Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial. JAMA. 2013 Apr 17;309(15):1622-31. doi: 10.1001/jama.2013.3527.
citation: Patel AN, Henry TD, Quyyumi AA, Schaer GL, Anderson RD, Toma C, East C, Remmers AE, Goodrich J, Desai AS, Recker D, DeMaria A; ixCELL-DCM Investigators. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. Lancet. 2016 Jun 11;387(10036):2412-21. doi: 10.1016/S0140-6736(16)30137-4. Epub 2016 Apr 5.
citation: Bonow RO, Maurer G, Lee KL, Holly TA, Binkley PF, Desvigne-Nickens P, Drozdz J, Farsky PS, Feldman AM, Doenst T, Michler RE, Berman DS, Nicolau JC, Pellikka PA, Wrobel K, Alotti N, Asch FM, Favaloro LE, She L, Velazquez EJ, Jones RH, Panza JA; STICH Trial Investigators. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011 Apr 28;364(17):1617-25. doi: 10.1056/NEJMoa1100358. Epub 2011 Apr 4.