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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 (S-CURE)

Primary Purpose

Ischemic Heart Disease

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CSWT+BMMSCs

CSWT+Sham operation

About this trial

This is an interventional treatment trial for Ischemic Heart Disease focused on measuring stem cells, ischemic heart disease.

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Shanghai Tenth People's Hospital, Tongji UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

CSWT+BMMSCs

CSWT+Sham operation

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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).

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.

Secondary Outcome Measures

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.

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).

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.

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.

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.

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).

Full Information

NCT ID

NCT03397095

First Posted

December 28, 2017

Last Updated

August 23, 2019

Sponsor

Shanghai 10th People's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03397095

Brief Title

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

Acronym

S-CURE

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Unknown status

Study Start Date

April 3, 2018 (Actual)

Primary Completion Date

December 1, 2019 (Anticipated)

Study Completion Date

April 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai 10th People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Heart Disease

Keywords

stem cells, ischemic heart disease.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CSWT+BMMSCs

Arm Type

Experimental

Arm Description

Arm Title

CSWT+Sham operation

Arm Type

Sham Comparator

Arm Description

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

Intervention Type

Combination Product

Intervention Name(s)

CSWT+BMMSCs

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

CSWT+Sham operation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change from baseline to 6 months follow-up in LVEF.

Description

The primary outcome will evaluate the change in left ventricular function as measured by echocardiography and D-SPECT for left ventricular ejection fraction (LVEF).

Time Frame

6 months

Title

Change from baseline to 6 months follow-up in infarct size.

Description

The primary outcome will evaluate the change in infarct size as measured by D-SPECT.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

6 months

Title

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

Description

Time Frame

6 months

Title

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

Description

A secondary objective will be the change from baseline to Month 6 in NYHA Classification in patients treated with BMMSCs compared to placebo.

Time Frame

6 months

Title

Percent of patients with adverse events.

Description

Time Frame

6 months

Title

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

Description

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.

Time Frame

6 months

Title

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

Description

Time Frame

6 months

Other Pre-specified Outcome Measures:

Title

Percent of patients with major adverse cardiac events (MACE)

Description

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.

Time Frame

6 months

Title

Average number of clinical events over 12 months post-treatment

Description

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.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yuxi Sun

Phone

+86 15216718171

zhggsmlsyx@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Dachun Xu, MD,PhD

Phone

+86 18917684045

xdc77@aliyun.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yawei Xu, MD,PhD

Organizational Affiliation

Shanghai 10th People's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shanghai Tenth People's Hospital, Tongji University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200072

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dachun Xu, MD,PhD

Phone

+86 18917684045

xdc77@aliyun.com

First Name & Middle Initial & Last Name & Degree

Yawei Xu, MD,PhD

Phone

+86 13916698181

xuyawei@tongji.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

16990384

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.

Results Reference

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PubMed Identifier

23592107

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. Erratum In: JAMA. 2013 May 15;309(19):1994.

Results Reference

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PubMed Identifier

27059887

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. Erratum In: Lancet. 2016 Jun 11;387(10036):2382.

Results Reference

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PubMed Identifier

21463153

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.

Results Reference

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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

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