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

NCT03397095 | Unknown Phase 1 DMC

• 1 other identifier: S-CURE
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Heart Disease

Keywords

stem cells, ischemic heart disease.

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Change from baseline to 6 months follow-up in exercise distance increment

  6 months

• Change from baseline to 6 months follow-up in quality of life measured by MLHFQ

  6 months

• Change from baseline to 6 months follow-up in NYHA Classification.

  6 months

• Percent of patients with adverse events.

  6 months

• Change from baseline to 6 months follow-up in exercise time increment.

  6 months

Other Outcomes (2)

• Percent of patients with major adverse cardiac events (MACE)

  6 months

• Average number of clinical events over 12 months post-treatment

  12 months

Study Arms (2)

CSWT+BMMSCs

EXPERIMENTAL

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

CSWT+Sham operation

SHAM COMPARATOR

Placebo group will receive a 3-month CSWT and a sham procedure.

Device: CSWT+Sham operation

Interventions

CSWT+BMMSCs COMBINATION_PRODUCT

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.

CSWT+BMMSCs

CSWT+Sham operation DEVICE

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.

CSWT+Sham operation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai 10th People's Hospital: lead

Study Sites (1)

Shanghai Tenth People's Hospital, Tongji University

Shanghai, Shanghai Municipality, 200072, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 16990384 BACKGROUND

• 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.

  PMID: 23592107 BACKGROUND

• 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.

  PMID: 27059887 BACKGROUND

• 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.

  PMID: 21463153 BACKGROUND

MeSH Terms

Conditions

Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Yawei Xu, MD,PhD

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuxi Sun

CONTACT

+86 15216718171; zhggsmlsyx@163.com

Dachun Xu, MD,PhD

CONTACT

+86 18917684045; xdc77@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 28, 2017
• First Posted: January 11, 2018
• Study Start: April 3, 2018
• Primary Completion: December 1, 2019
• Study Completion: April 1, 2022
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)