A Phase III randomized, double-blinded, placebo-controlled trial to investigate the impact of intra-coronary transfusion of G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC) therapy in patients with diffuse coronary artery disease who are not candidates for coronary artery intervention
| ISRCTN | ISRCTN14054375 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14054375 |
| Secondary identifying numbers | TFDA No. 106IND02037 |
- Submission date
- 14/06/2018
- Registration date
- 26/06/2018
- Last edited
- 08/01/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Heart disease is the second leading cause of death worldwide. Although the treatment of this disease has been extensively investigated, effective treatment options are still limited. Therefore, it is of utmost important for clinicians to find an effective treatment for these diseases. A type of stem cells found in the blood, known as G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPCs), have been shown to improve heart disease outcomes. The aim of this study is to find out whether CPCs can improve heart function for patients with heart disease who are not candidates for coronary artery interventions (PCI or CABG).
Who can participate?
Patients aged 20-80 years-old with heart disease who are not candidates for PCI or CABG
What does the study involve?
Participants are randomly allocated into the experimental group or the control group. The experimental group are treated with CPCs. The control group are treated with plasma (blood). All participants are followed up for one year after the treatment to assess their heart function.
What are the possible benefits and risks of participating?
The possible benefits are improvement of heart function and quality of life. The risks include arrhythmia, increased risk of angina or heart failure, stroke, claudication (pain in the legs due to reduced blood flow), hemorrhage, anemia, renal insufficiency (kidney failure) and electrolyte imbalance. The possible side effects from the CPC therapy include deterioration of brain function, recurrent stroke, heart problems, blockage of arteries, bleeding, anemia, deterioration of kidney function, gastrointestinal (gut) complications, electrolyte (minerals in the body) imbalance, sepsis (blood poisoning) and cancer.
Where is the study run from?
Kaohsiung Chang Gung Memorial Hospital (Taiwan)
When is the study starting and how long is it expected to run for?
November 2017 to August 2026
Who is funding the study?
Chang Gung Medical Research Program Grant (Taiwan)
Who is the main contact?
Dr Hon-Kan Yip
han.gung@msa.hinet.net
Contact information
Public
No. 123, Ta Pei Road Niao Sung District
Kaohsiung City
83301
Taiwan
| Phone | +886 (0)7 7317123 ext. 8300 |
|---|---|
| han.gung@msa.hinet.net |
Study information
| Study design | Prospective single-center interventional trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Application of G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC) for patients with diffuse coronary artery disease (CAD) who are non-candidates for coronary artery intervention: a phase III clinical trial for evaluation of efficacy |
| Study acronym | CPC for patients with CAD |
| Study objectives | G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC) may be a therapeutic option for patients with diffuse Coronary Artery Disease (CAD) and non candidates for coronary artery intervention. |
| Ethics approval(s) |
Approved 20/09/2023, Chang Gung Medical Foundation, Institutional Review Board (199, TUNG HWA NORTH ROAD, TAIPEI, 10507, Taiwan; +886 (03) 3196200; dog111443@cgmh.org.tw), ref: 201700248A0C505 |
| Ethics approval additional information | 2. Taiwan FDA, 22/05/2018, No. 106IND02037 |
| Health condition(s) or problem(s) studied | Diffuse Coronary Artery Disease (CAD) and non candidates for coronary artery intervention |
| Intervention | Patients are randomised into the experimental group and the control group (2:1) based on an automatically generated random number table. Experimental group: G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC): 3.0 x 10(7) cells/kg (n=64) Control group: plasma from subjects (n=32) All subjects will be followed up for one year after the treatment. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Hematopoietic stem/progenitor cells (CPC) |
| Primary outcome measure | Left ventricular ejection fraction (LVEF) examined by 3D echo and cardiac MRI at baseline (D6) and 12 months |
| Secondary outcome measures | 1. The incidence of death monitored from baseline (D6) to 12 months during one-year follow-up 2. The incidence of major cardiac events (i.e., defined as the occurrence of myocardial infarction, congestive heart failure, or refractory angina) monitored from baseline (D6) to 12 months during one-year follow-up 3. Heart failure evaluated according to NYHA functional class. The left ventricular ejection fraction (LVEF) is measured by cardiac ultrasonography at baseline and each revisit (1 week, 1 month, 3 months, 6 months, 9 months, and 12 months) to evaluate the left ventricular systolic function. The heart function of subjects (NYHA Functional Class) from mild to severe is divided from Class I to Class IV for assessing the improvement of heart failure 4. The symptom severity of angina pectoris assessed according to the Canadian cardiovascular society grading system at baseline and each revisit (1 week, 1 month, 3 months, 6 months, 9 months, and 12 months). Exertion-induced angina from mild to severe is divided from Class I to Class IV for assessing the improvement of angina pectoris |
| Overall study start date | 30/11/2017 |
| Completion date | 20/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 20 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | 96 subjects (64 subjects for treatment group and 32 subjects for control group) |
| Key inclusion criteria | Age between 20-80 y/o, coronary syndrome, subjects with severe diffuse coronary artery disease who have been diagnosed by cardiac catheterization, not suitable for cardiac catheterization or surgical coronary artery bypass surgery after cardiac internist and surgeons evaluate, and receiving optimal medical therapy, including antiplatelet therapy (aspirin or clopidogrel), ACEI/ARB, beta-blocker, calcium channel blocker, nitrates, etc. The symptom of chest pain is still evaluated as Canadian Cardiovascular Society class II-IV Angina. LVEF ≤55 % examined by 3D echo (i.e. LVEF ≥60 % indicates normal. After stem cell treatment, the LVEF is improved up to 5 %, unchanged or continually deteriorated. Therefore, the criteria of enrollment of LVEF is ≤55 %). Patients are willing to accept the G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC) treatment through cardiac catheterization, and are willing to join this study follow-up. The severe diffuse coronary artery disease is defined as follows: 1. Clinical symptoms of angina (Canadian Cardiovascular Society class II-IV) 2. Tl-201 scan presents reversible ischemic changes (results should be adopted within 6 months) 3. Highly diffuse vascular lesions show in angiography results (continuous normal segmental vessels length no longer than 10 mm), and the degree of stenosis more than 75% (results can be adopted within 6 months) 4. Due to vascular occlusion showed diffuse and too small, not to be suitable for PCI (angioplasty nowhere to be implemented) or CABG (which can be accessed at no normal blood vessels) analyzed by PCI and CABG experts. The vessel must be severe diffuse stenosis (unsuitable for CABG) |
| Key exclusion criteria | 1. Age <20 y/o or >80 y/o 2. Pregnant or breastfeeding women 3. No adventitious agents, ex. HIV infection, HBV and HCV carriers (HBsAg+ or anti-HCV +) (subjects without examination of HIV, HBV and HCV are excluded) 4. Myocardial infarction within 3 months, stent placement within 3 months 5. Severe aortic or mitral stenosis 6. Asthma and not suitable for cardiac catheterization treatment (including NYHA functional class IV) 7. Malignant or hematologic disease. Severe disease with life span less than one year 8. Chronic kidney disease (CCr <20 ml/min) and patients receiving dialysis 9. Under immunosuppressive medications 10. Autoimmune diseases 11. Contraindication to G-CSF 12. The subject previously received cell therapy 13. Participating in another clinical study and planning to participate in another clinical study during the course of this study |
| Date of first enrolment | 01/06/2018 |
| Date of final enrolment | 01/08/2026 |
Locations
Countries of recruitment
- Taiwan
Study participating centre
Kaohsiung
83301
Taiwan
Sponsor information
Hospital/treatment centre
No.5, Fuxing St.
Guishan Dist.
Taoyuan
33305
Taiwan
"ROR" |
https://ror.org/00k194y12 |
|---|
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
08/01/2024: The following changes were made to the trial record:
1. The drug name was added.
2. The intention to publish date was changed from 31/12/2027 to 31/12/2026.
29/12/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2022 to 01/08/2026.
2. The overall trial start date has been changed from 11/01/2017 to 30/11/2017 and the plain English summary updated accordingly.
3. The overall trial end date has been changed from 31/12/2023 to 20/08/2026 and the plain English summary updated accordingly.
4. The intention to publish date has been changed from 31/12/2024 to 31/12/2027.
01/03/2019: Internal review.
