Condition category
Circulatory System
Date applied
14/06/2018
Date assigned
26/06/2018
Last edited
25/06/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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?
January 2017 to December 2023

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

Trial website

Contact information

Type

Public

Primary contact

Dr Hon-Kan Yip

ORCID ID

Contact details

No. 123
Ta Pei Road Niao Sung District
Kaohsiung City
83301
Taiwan
+886 (0)7 7317123 ext. 8300
han.gung@msa.hinet.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

TFDA No. 106IND02037

Study information

Scientific title

Application of G-CSF mobilized autologous circulating hematopoietic stem/progenitor cells (CPC) for patients with diffuse coronary artery disease (CAD) and non candidates for coronary artery intervention: a phase III clinical trial for evaluation of efficacy

Acronym

CPC for patients with CAD

Study hypothesis

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

1. Chang Gung Memorial Hospital IRB, 23/03/2018, No. 201700248A0C601
2. Taiwan FDA, 22/05/2018, No. 106IND02037

Study design

Prospective single-center interventional trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

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 107 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

Phase

Drug names

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 trial start date

11/01/2017

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant 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)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

96 subjects (64 subjects for treatment group and 32 subjects for control group)

Participant 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

Recruitment start date

01/06/2018

Recruitment end date

31/12/2022

Locations

Countries of recruitment

Taiwan

Trial participating centre

Kaohsiung Chang Gung Memorial Hospital
No.123, Ta Pei Road, Niao Sung District
83301
Taiwan

Sponsor information

Organisation

Chang Gung Memorial Hospital, Chang Gung Medical Foundation

Sponsor details

No.5
Fuxing St.
Guishan Dist.
Taoyuan
33305
Taiwan

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Chang Gung Medical Research Program Grant

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal before 31/12/2024.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes