Safety and Efficacy of Autologous Cardiopoietic Cells for Treatment of Ischemic Heart Failure.

NCT ID: NCT01768702

Last Updated: 2018-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2017-08-31

Brief Summary

Evaluation the safety and efficacy of C3BS-CQR-1 by comparing the overall response to standard of care and C3BS-CQR-1 relative to standard of care and a sham procedure.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control

Sham, no injection

Group Type: SHAM_COMPARATOR

Sham, no injection

Intervention Type: BIOLOGICAL

Mimic the injection procedure trough insertion of a sham catheter. No injection actually performed

C3BS-CQR-1 Treated

Injection of C3BS-CQR-1

Group Type: EXPERIMENTAL

Injection of C3BS-CQR-1

Intervention Type: BIOLOGICAL

Injection of the C3BS-CQR-1 using the C-Cath® injection catheter.

Interventions

Injection of C3BS-CQR-1

Injection of the C3BS-CQR-1 using the C-Cath® injection catheter.

Intervention Type: BIOLOGICAL

Sham, no injection

Mimic the injection procedure trough insertion of a sham catheter. No injection actually performed

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 and < 80 years.

2. Systolic dysfunction with left ventricular ejection fraction (LVEF) ≤ 35% as assessed by echocardiography.

3. Ischemic heart failure without known need for revascularization.

4. Total MLHFQ score > 30.

5. Ability to perform a 6 minute walk test > 100 m and ≤ 400 m.

6. History of hospitalization for heart failure (HF) within 12 months prior to screening or treatment in an outpatient clinic with intravenous vasoactive therapy (including vasodilators, positive inotropic agents and vasopressors) or diuretics for worsening Heart Failure within 12 months prior to screening.

7. Be or must have been within the previous 12 months in New York Heart Association (NYHA) Class III or IV or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 4, 5, 6 or 7, and at the time of inclusion, must be at least in NYHA Class II or greater.

8. Use of ACE inhibitor and/or angiotensin receptor blocker (ARB); and beta blocker, for at least 3 months prior to screening visit, unless intolerant or contraindicated.

9. Stable dosing of ACE inhibitor, angiotensin receptor blocker , beta blocker, aldosterone blocker,and diuretics for at least one month prior to screening visit, defined as ≤50% change in total dose of each agent.

10. Willing and able to give written informed consent.

Exclusion Criteria

1. Women who are pregnant, confirmed by a positive urine or serum human chorionic gonadotropin laboratory test at screening.

2. Women of child-bearing potential without a negative serum or urine pregnancy test at screening. Women who are postmenopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH level > 40 mIU/mL or 6 weeks post surgical bilateral oophorectomy) or surgically sterile are not considered to be of child-bearing potential. Reliable contraception includes surgical sterilization, hormonal contraception, or doublebarrier methods.

3. Men refusing to exercise a reliable form of contraception.

4. Myocardial infarction, unstable angina or percutaneous coronary intervention (PCI) within 90 days prior to screening, or coronary artery bypass graft surgery within 180 days prior to screening.

5. Patient on a cardiac transplant list or previously received any solid organ transplant.

6. Previously underwent cardiac surgery with remodeling procedure, left ventricular assist device placement or cardiomyoplasty. This exclusion does not apply to patients who underwent ventricularplasty without placement device more than one year ago.

7. Patient has undergone cardiac resynchronization therapy within 6 months prior to screening.

8. Severe uncontrolled HF requiring need for intensive intravenous diuretics or inotropic support within 1 month prior to screening.

9. Inability to perform a 6 minute walk test due to physical limitations other than HF including:

1. Severe peripheral vascular disease

2. Severe pulmonary disease or chronic obstructive pulmonary disease limiting exercise

3. Orthopedic limitations, severe muscular diseases, any other joint or muscular disease or neurological disorder (such as an old stroke or neuropathy) limiting the ability to walk for 6 minutes.

10. Dependence on chronic oral steroid therapy.

11. Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to screening.

12. Active myocarditis, constrictive pericarditis, restrictive, hypertrophic or congenital cardiomyopathy.

13. BMI < 19 or > 45.

14. Left ventricular thrombus.

15. Left ventricular (LV) wall thickness < 8mm visualized in more than 50% of LV, and defined as a "LV no-go zone".

16. LV aneurysm or candidate for surgical aneurysmectomy.

17. Sustained ventricular tachycardia or ventricular fibrillation which led to automatic implantable cardioverter/defibrillator (AICD) therapy (shock) within 3 months prior to screening.

18. Primary significant organic valvular heart disease.

19. Moderate to severe aortic valve disease precluding catheter entry into the LV.

20. Mechanical prosthetic valve in aortic or mitral position.

21. Chronic infection or active malignancy.

22. Patient has compromised renal function as reflected by a serum creatinine level >3.0 mg/dL (>0.265 mmol/L) or is currently on dialysis.

23. Hematocrit < 28%.

24. Atherosclerosis and/or tortuosity of the aorta, iliac or femoral arteries of a degree that could impede or preclude the safe retrograde passage of the delivery catheter.

25. Chronic immunosuppressive therapy due to inflammatory or systemic disease.

26. Patient tested positive for HIV 1 or 2, Hepatitis B or C, human T-cell lymphotrophic virus (HTLV) 1 or 2 (if required by regulations) or syphilis.

27. Exposure to any previous experimental cell or angiogenic therapy and/or myocardial laser therapy and/or therapy with another investigational drug within 60 days prior to screening or enrollment in any concurrent study that may confound the results of this study.

28. Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate.

29. Any illness other than congestive heart failure which might reduce life expectancy to less than 2 years from screening.

30. Known and relevant allergies and/or hypersensitivities to Dextran or other plasma volume expanders to include Gentran, Hyskon and Macrodex.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celyad Oncology SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

André Terzic, MD

Role: STUDY_CHAIR

Mayo Clinic, Division of Cardiovascular Diseases, Rochester (MN, USA)

Jozef Bartunek, MD

Role: STUDY_CHAIR

OLV Ziekenhuis Aalst (Belgium)

Locations

OLV Ziekenhuis Aalst

Aalst, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Hopital Civil Marie Curie

Lodelinsart, , Belgium

AZ Glorieux

Ronse, , Belgium

CHU Mont-Godinne

Yvoir, , Belgium

City Clinic Cardiology Center Multiprofile Hospital for Active Treatment

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment 'Alexandrovska' EAD

Sofia, , Bulgaria

Gottsegen György Országos Kardiológiai Intézet - Felnőtt Kardiológiai Osztály

Budapest, , Hungary

Semmelweis Egyetem - Városmajori Szív- és Érgyógyászati Klinika

Budapest, , Hungary

MH Egészségügyi Központ Kardiológiai Osztály

Budapest, , Hungary

Debreceni Egyetem Orvos - és Egészségtudomanyi Centrum

Debrecen, , Hungary

Pécsi Tudományegyetem Klinikai Központ - Szívgyógyászati Klinika

Pécs, , Hungary

Barzilai Medical Center - Cardiology Unit

Ashkelon, , Israel

Hillel Yaffe Medical Center

Hadera, , Israel

Western Galilee Hospital

Nahariya, , Israel

Nazareth Hospital EMMS

Nazareth, , Israel

Ziv Medical Center - Heart Institute

Safed, , Israel

A.O. Spedali Civili di Brescia

Brescia, , Italy

AOUI Verona - Borgo Trento Hospital

Verona, , Italy

Uniwersyteckie Centrum Kliniczne, KliniczneCentrum Kardiologii

Gdansk, , Poland

Górnośląskie Centrum Medyczne Śląskiej Akademii Medycznej

Katowice, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie

Krakow, , Poland

Biegański Hospital

Lodz, , Poland

Clinic of Emergency Internal Medicinne Military Medical Academy

Belgrade, , Serbia

Clinical Center of Serbia - Cardiology Clinic

Belgrade, , Serbia

Clinical Centre of Serbia, Cardiology Clinic

Belgrade, , Serbia

Clinical Hospital Center Zvezdara - Cardiology Clinic

Belgrade, , Serbia

Clinical Hospital Center Bezanijska Kosa, Cardiology Dept.

Belgrade, , Serbia

Clinical Center of Kragujevac,

Kragujevac, , Serbia

Hospital Universitario Germans Trias i Pujol

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria - Campus de Teatinos s/n

Málaga, , Spain

Cardiocentro Ticino

Lugano, , Switzerland

Countries

Belgium; Bulgaria; Hungary; Israel; Italy; Poland; Serbia; Spain; Switzerland

References

Bartunek J, Davison B, Sherman W, Povsic T, Henry TD, Gersh B, Metra M, Filippatos G, Hajjar R, Behfar A, Homsy C, Cotter G, Wijns W, Tendera M, Terzic A. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design. Eur J Heart Fail. 2016 Feb;18(2):160-8. doi: 10.1002/ejhf.434. Epub 2015 Dec 14.

Reference Type: DERIVED

PMID: 26662998 (View on PubMed)

Other Identifiers

2011-001117-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C3BS-C-11-01

Identifier Type: -

Identifier Source: org_study_id