Clinical trial NCT01768702: Safety and Efficacy of Autologous Cardiopoietic Cells for Treatment of Ischemic Heart Failure.
Official title: Efficacy and Safety of Bone Marrow-derived Mesenchymal Cardiopoietic Cells (C3BS-CQR-1) for the Treatment of Chronic Advanced Ischemic Heart Failure.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Keywords: Chronic Heart Failure of Ischemic Origin
Lead sponsor: Celyad Oncology SA
Sponsor class: INDUSTRY
First posted: 2013-01-15
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

Eligible patients must meet all of the following 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 (summarized):

Eligible patients must meet none of the following 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.

Primary outcomes:
measure: Efficacy between groups post-index procedure
timeFrame: 39 weeks post-index
Secondary outcomes:
measure: Efficacy and safety between groups post-index procedure
timeFrame: 52 and 104 weeks post-index
Other outcomes:
measure: Efficacy and safety between groups post-index procedure
timeFrame: 39 and 52 weeks post-index
Locations:
city: Aalst
country: Belgium
facility: OLV Ziekenhuis Aalst
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Lodelinsart
country: Belgium
facility: Hopital Civil Marie Curie
city: Ronse
country: Belgium
facility: AZ Glorieux
city: Yvoir
country: Belgium
facility: CHU Mont-Godinne
city: Sofia
country: Bulgaria
facility: City Clinic Cardiology Center Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment 'Alexandrovska' EAD
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet - Felnőtt Kardiológiai Osztály
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - Városmajori Szív- és Érgyógyászati Klinika
city: Budapest
country: Hungary
facility: MH Egészségügyi Központ Kardiológiai Osztály
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos - és Egészségtudomanyi Centrum
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ - Szívgyógyászati Klinika
city: Ashkelon
country: Israel
facility: Barzilai Medical Center - Cardiology Unit
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Hospital
city: Nazareth
country: Israel
facility: Nazareth Hospital EMMS
city: Safed
country: Israel
facility: Ziv Medical Center - Heart Institute
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia
city: Verona
country: Italy
facility: AOUI Verona - Borgo Trento Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, KliniczneCentrum Kardiologii
city: Katowice
country: Poland
facility: Górnośląskie Centrum Medyczne Śląskiej Akademii Medycznej
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie
city: Łódź
country: Poland
facility: Biegański Hospital
city: Belgrade
country: Serbia
facility: Clinic of Emergency Internal Medicinne Military Medical Academy
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia - Cardiology Clinic
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Cardiology Clinic
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara - Cardiology Clinic
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa, Cardiology Dept.
city: Kragujevac
country: Serbia
facility: Clinical Center of Kragujevac,
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria - Campus de Teatinos s/n
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
Study officials:
affiliation: Mayo Clinic, Division of Cardiovascular Diseases, Rochester (MN, USA)
name: André Terzic, MD
role: STUDY_CHAIR
affiliation: OLV Ziekenhuis Aalst (Belgium)
name: Jozef Bartunek, MD
role: STUDY_CHAIR
References:
citation: 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.