Clinical trial NCT02059512: Autologous Bone Marrow Mononuclear Cells in the Combined Treatment of Coronary Heart Disease
Official title: Influence of the Administration of Autologous Bone Marrow Mononuclear Cells for the Duration of Functioning Aorto-coronary Bypass Grafts in the Surgical Treatment of Coronary Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Heart Disease
Bone Marrow Cells
Coronary Artery Bypass Grafting (CABG)
Heart Failure, Diastolic
Keywords: ischemic heart disease
bone marrow cells
coronary artery bypass grafting (CABG)
reperfusion injury
myocardial dysfunction, diastolic
Heart Failure, Diastolic
transplantation of autologous mononuclear cells
intramyocardial administration
intracoronary administration
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2014-02-11
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Potential participants in this study were all patients admitted for planned coronary artery bypass grafting under extracorporeal circulation and who, according to angiographic examination, had 3 or more stenotic coronary arteries. The final decision on the inclusion of each individual patient in this study was determined taking into account the inclusion criteria. The study was conducted according to the approved protocol as a randomized, blind, placebo controlled.
Primary purpose: TREATMENT

Brief summary: The purpose of this study evaluate the effect of the method of administration of autologous bone marrow mononuclear cells for the duration of of functioning aorto-coronary bypass grafts in the surgical treatment of coronary heart disease, to assess the degree of effectiveness depending on the method of transplantation (intramyocardial, intracoronary, combined).

Detailed description: Additional estimation of safety:

1. Assessment of EuroScore II.
2. Hospital Stay.
3. The duration of stay in the intensive care unit.
4. Restoration of cardiac rhythm at the end of the main stage of operation (defibrillation/ self-recovery).
5. The time of extracorporeal circulation.
6. Time of anoxia.
7. Volume abjointed (drainage) postoperative day 1, day 3
8. Troponin I, CPK-MB, Myoglobin at 1, 3 postoperative days.
9. Hb/ HCT/K+ at the end of cardiopulmonary bypass (CPB) and Hb/ HCT/K+/ ABC at the end of the operation.
10. Assessment of the degree of manifestation of a systemic inflammatory reaction in the postoperative period - leukocytes (Leu), CRP
11. Postoperative complications (hydrothorax, hydropericardium, arrhythmias, resternotomy).
12. Echocardiography at 7-14 days after surgery.

Estimation of efficiency:

1. Evaluation of systolic and diastolic myocardial function. Assessment of myocardial perfusion and metabolism (before and after treatment) - Speckle tracking echocardiography.
2. Patency of grafts within a specified time of treatment (angiography).
3. Dependence and duration of positive clinical effect on the amount of injected cell material.
4. Evaluation of the quality of life (Minnesota questionnaire, Seattle questionnaire, SF- 36 questionnaire).
5. All-cause Mortality Associated With the Progression of Basic
6. Disease.Dynamics of the functional class of angina.
7. Dynamics of the functional class of heart failure.
8. Dynamics of test data with a 6-minute walk.

Predicting the results of treatment (the effect of a number of parameters):

1. Age.
2. Gender.
3. The body mass index.
4. Diabetes.
5. Smoking.
6. Family history of cardiovascular events.
7. Duration of ischemic heart disease.
8. Serum total cholesterol (+ fractions).
9. Leukocytosis and CRP level (initial level and rate of decrease in the postoperative period).
10. The level of creatinine.
11. The presence / absence of extracardiac arteriopathy.
12. The intramyocardial or intracoronary injection of BM-MNCs.
13. Assessment of the bone marrow: the number of nucleated cells, CD34 +, CD133 +.

Eligibility criteria: Inclusion Criteria:

* Men and women from 18 to 80 years
* Patients with angina pectoris III-IV functional class
* According to angiographic examination, the presence of 3 or more stenotic coronary arteries
* Aorto-coronary bypass surgery under cardiopulmonary bypass
* Patients signed informed consent

Exclusion Criteria:

* Intolerance of heparin and HES.
* Hypothyroidism and hyperthyroidism.
* Associated pathology with a projected lifespan limitation to 3 years.
* infection diseases
* Simultaneous participation in another study.
* Pregnancy.
* Severe mental disorder.
* Refusal of a patient to participate in the study.

Primary outcomes:
measure: Assessment of the Initial Risk of Surgery (EuroScore II).
timeFrame: Before CABG surgery at baseline.
measure: Length of Hospital Stay. Length of Stay in the Intensive Care Unit.
timeFrame: Primary hospitalization for planned CABG.
measure: The Severity of the Systemic Inflammatory Response in the Postoperative Period (Leukocytosis).
timeFrame: The parameters were evaluated initially at baseline in the postoperative period - an interval of 0-6 hours, 12-18 hours, 18-24 hours, 48 hours, 72 hours, 96 hours, 7 days and 14 days.
measure: Assessment of the Degree of General Inflammatory Response (C-reactive Protein (CRP)),
timeFrame: Initial data, control point in the interval 4-6 days of the postoperative period, control point in the interval 12-14 days of the postoperative period.
measure: The Volume of Discharge Through the Drains in the Early Postoperative Period.
timeFrame: Evaluation of these data - for the time spent in the intensive care unit before removing the drains.
measure: Dynamics of Markers of Myocardial Damage (Troponin I, Myoglobin).
timeFrame: 1 and 3 days of the postoperative period.
measure: Dynamics of Markers of Myocardial Damage (Creatine Phosphokinase Fraction MB (CPK-MB)).
timeFrame: 1 and 3 days of the postoperative period.
measure: Intraoperative Assessment of Homeostasis (Hemoglobin (Hb).
timeFrame: Intraoperative data.
measure: Intraoperative Assessment of Homeostasis (Hematocrit (HCT)).
timeFrame: Intraoperative data.
measure: Intraoperative Assessment of Homeostasis (К+).
timeFrame: Intraoperative data.
measure: Cardiopulmonary Bypass Time.
timeFrame: Intraoperative data.
measure: Time of Aortic Clamping (Anoxia).
timeFrame: Intraoperative data.
measure: Assessment of Complications in the Postoperative Period. Additional Estimation of Safety.
timeFrame: Postoperative period.
measure: Left Ventricular Ejection Fraction - Echocardiography - Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.
timeFrame: 7-14 days of the postoperative period
measure: Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment - Echocardiography (Size of the Left Ventricle - Index). Additional Estimation of Safety.
timeFrame: 7-14 days after surgery
measure: Volume of the Left Ventricle - Index - Echocardiography. Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.
timeFrame: 7-14 days after surgery
measure: Restoration of the Heart Rate After the Completion of the Main Stage of the Surgical Intervention. Additional Estimation of Safety.
timeFrame: Upon completion of the main stage of surgery.
Secondary outcomes:
measure: All-cause Mortality Associated With the Progression of Basic Disease.
timeFrame: 12 months after surgery
measure: Quality of Life. Evaluation of the Quality of Life (Minnesota Questionnaire (MHFLQ), Seattle Questionnaire (SAQ), SF-36 Questionnaire). Estimation of Efficiency.
timeFrame: At baseline and after one year.
measure: Assessment of the Functional Class of Exertional Angina at 12 Months After Surgical Treatment.
timeFrame: up to 12 months
measure: Dynamics of the Functional Class of Heart Failure (NYHA). Estimation of Efficiency.
timeFrame: Assessment of the dynamics at 12 months after treatment.
measure: Evaluation of the Left Ventricular Ejection Fraction 12 Months After Treatment.
timeFrame: 12 months after treatment.
measure: Estimation of the Index of Linear Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
timeFrame: 12 months after the treatment.
measure: Estimation of the Index of Volumetric Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
timeFrame: 12 Months After the Treatment
measure: Assessment of Left Ventricular Diastolic Function - Peak E of Transmitral Flow and Peak А of Transmitral Flow 12 Months After Treatment.
timeFrame: 12 months after treatment.
measure: Assessment of Left Ventricular Diastolic Function E/A - 12 Months After Treatment.
timeFrame: 12 months after treatment
measure: Assessment of Left Ventricular Diastolic Function - DT and IVRT 12 Months After Treatment.
timeFrame: 12 Months After Treatment.
measure: Distance Traveled in the 6-minute Walk Test. Test Results With 6 Minute Walk
timeFrame: initially and after 12 months
measure: The Number of Functioning Grafts 12 Months After CABG. Patency of Grafts Within a Specified Time of Treatment (Angiography).
timeFrame: up to 12 months
measure: Analysis of the Effect of Left Ventricular Diastolic Dysfunction on the Patency of the Grafts.
timeFrame: up to 12 months
Other outcomes:
measure: The Volume of Cellular Material (Cytosis).
timeFrame: Initial data at the time of collection of bone marrow cells.
measure: The Amount of Cell Material (Percentage).
timeFrame: Initial data at the time of collection of bone marrow cells.
measure: Smoking as a Factor That Negatively Affects the Results of the Test With a 6-minute Walk in Dynamics.
timeFrame: 12 months after treatment.
Locations:
city: St. Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: First Pavlov State Medical University of St. Petersburg.
name: Vladimir V Komok, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Komok V.V., Bunenkov N.S., Beliy S.A., Pizin V.M., Kondratev V.M., Dulaev А.V., Lukashenko V.I., Kobak A.E., Maksimova T.S., Sergienko I.P., Parusova E.V., Smirnova L.A., Babenko E.V., Afanasev B.V., Nemkov A.S., Khubulava G.G. Assessment of safety of additional transplantation of autologous bone marrow mononuclear cells in the combined treatment of coronary heart disease. Results from a randomized, blind, placebo-controlled trial (TAMIS). Russian Journal of Transplantology and Artificial Organs. 2019;21(2):112-120. (In Russ.) https://doi.org/10.15825/1995-1191-2019-2-112-120
citation: Komok V.V., Bunenkov N.S., Beliy S.A., Pizin V.M., Kondratev V.M., Dulaev A.V., Kobak A.E., Maksimova T.S., Sergienko I.P., Parusova E.V., Smirnova L.A., Babenko E.V., Afanasev B.V., Nemkov A.S., Khubulava G.G. Evaluation of the effectiveness of combined treatment of coronary heart disease - coronary artery bypass grafting, transplantation of autologous bone marrow mononuclear cells: a randomized, double-blind, placebo-controlled study. Russian Journal of Transplantology and Artificial Organs. 2019;21(4):54-66. https://doi.org/10.15825/1995-1191-2019-4-54-66