Autologous Bone Marrow Mononuclear Cells in the Combined Treatment of Coronary Heart Disease

NCT02059512 | Completed Results DMC

• 1 other identifier: NBK-2901-AMNKM
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (17)

• Assessment of the Initial Risk of Surgery (EuroScore II).

  EuroScoreII is intended to assess the risk of adverse outcome of coronary artery bypass grafting. Assessment factors: age, sex, serum creatinine, extracardiac artery disease, chronic lung disease, severe neurological disorders, previous cardiac surgery, previous myocardial infarction, left ventricular dysfunction, diabetes mellitus, pulmonary hypertension, IV class of angina severity, active endocarditis, unstable angina, surgery, critical condition of the patient before surgery, type of surgery. The higher the percentage, the higher the risk of surgery.

  Before CABG surgery at baseline.

• Length of Hospital Stay. Length of Stay in the Intensive Care Unit.

  The results were obtained from the analysis of primary data.

  Primary hospitalization for planned CABG.

• The Severity of the Systemic Inflammatory Response in the Postoperative Period (Leukocytosis).

  Assessment of the severity of the systemic inflammatory response during hospital stay after surgery. Assessment of the level of inflammation by the severity of an increase in leukocytes (leukocytosis). Leukocytosis - an increase in the number of leukocytes per unit volume of blood. The norm of leukocytes in the blood is 5.5-8.810\^9 /l. For adults, leukocytosis is considered to be an increase in the number of leukocytes in the blood of more than 9.0\*10\^9 / l In the statistical analysis, the grouping of indicators in the indicated intervals was used, in view of the individual characteristics of the course of the postoperative period in each case.

  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.

• Assessment of the Degree of General Inflammatory Response (C-reactive Protein (CRP)),

  Results of dynamic control of laboratory parameters of CRP. C-reactive protein. This fraction of plasma proteins increases in the presence of an inflammatory process in the body. It is synthesized in response to the ingestion of toxins of pathological microorganisms into the bloodstream and neutralizes them by binding them. In addition, it appears when the body's own cells are destroyed in the event of necrosis, tumor disintegration or extensive trauma, inactivating the resulting products. In addition to eliminating toxins, CRP triggers a cascade of immune responses aimed at eliminating pathologically altered structures. Normally absent (or less than 0.4 mg / l). In the statistical analysis, the grouping of indicators in the indicated intervals was used, in view of the individual characteristics of the course of the postoperative period in each case.

  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.

• The Volume of Discharge Through the Drains in the Early Postoperative Period.

  A daily assessment of the discharge by drainage before removal was carried out. It was carried out to assess the possible development of an excessive inflammatory reaction (polyserositis phenomena) in response to the transplantation of autologous bone marrow mononuclear cells.

  Evaluation of these data - for the time spent in the intensive care unit before removing the drains.

• Dynamics of Markers of Myocardial Damage (Troponin I, Myoglobin).

  Assessment of the severity of the period of ischemia / reperfusion. And the effect of autologous bone marrow mononuclear cells transplantation on these indicators.

  1 and 3 days of the postoperative period.

• Dynamics of Markers of Myocardial Damage (Creatine Phosphokinase Fraction MB (CPK-MB)).

  Assessment of the severity of the period of ischemia / reperfusion. And the effect of autologous bone marrow mononuclear cells transplantation on these indicators.

  1 and 3 days of the postoperative period.

• Intraoperative Assessment of Homeostasis (Hemoglobin (Hb).

  These parameters were evaluated at the end of the cardiopulmonary bypass and at the end of the surgery. The interval between indicators is on average from 60 to 120 minutes.

  Intraoperative data.

• Intraoperative Assessment of Homeostasis (Hematocrit (HCT)).

  These parameters were evaluated at the end of the cardiopulmonary bypass and at the end of the surgery. The interval between indicators is on average from 60 to 120 minutes.

  Intraoperative data.

• Intraoperative Assessment of Homeostasis (К+).

  These parameters were evaluated at the end of the cardiopulmonary bypass and at the end of the surgery. The interval between indicators is on average from 60 to 120 minutes.

  Intraoperative data.

• Cardiopulmonary Bypass Time.

  Intraoperative data.

• Time of Aortic Clamping (Anoxia).

  Estimation of the time from the moment the clamp is applied to the aorta (complete clamping of the aorta) to the removal of the clamp from the aorta.

  Intraoperative data.

• Assessment of Complications in the Postoperative Period. Additional Estimation of Safety.

  The presence of complications in the postoperative period (Hydrothorax, Hydropericardium, Cardiac arrhythmias - atrial fibrillation / atrial flutter).

  Postoperative period.

• Left Ventricular Ejection Fraction - Echocardiography - Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.

  Evaluation of myocardial contractility according to echocardiography, in particular the left ventricular ejection fraction, was carried out within 7-14 days of the postoperative period, depending on the patient's clinical condition, as well as the maximum degree of information content of this study. The lower the indicator, the worse the prognosis of an unfavorable outcome.

  7-14 days of the postoperative period

• Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment - Echocardiography (Size of the Left Ventricle - Index). Additional Estimation of Safety.

  Assessment of myocardial contractility according to echocardiography, in particular the size of the left ventricle - its index, was carried out within 7-14 days of the postoperative period, depending on the clinical condition of the patient, as well as on the maximum information content of this study. The higher the indicator (left ventricular size - index), the worse the prognosis of an unfavorable outcome. The index is used as an indicator of payment to obtain a more reliable result (taking into account the individual characteristics of each patient). index - left ventricular size (mm.)/ body mass index (kg/m\^2).

  7-14 days after surgery

• Volume of the Left Ventricle - Index - Echocardiography. Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.

  Evaluation of myocardial contractility according to echocardiography, in particular volume of the left ventricle - index was carried out within 7-14 days of the postoperative period, depending on the patient's clinical condition, as well as the maximum degree of information content of this study. The greater the figure (volume of the left ventricle - index), the worse the prognosis of adverse outcome. The index is used as an indicator of the payment to obtain a more reliable result (taking into account individual characteristics of each patient). index - volume of the left ventricle (ml.)/ body mass index (kg / m\^2).

  7-14 days after surgery

• Restoration of the Heart Rate After the Completion of the Main Stage of the Surgical Intervention. Additional Estimation of Safety.

  The need to perform defibrillation to restore sinus rhythm, at the end of the main stage of surgery.

  Upon completion of the main stage of surgery.

Secondary Outcomes (13)

• All-cause Mortality Associated With the Progression of Basic Disease.

  12 months after surgery

• Quality of Life. Evaluation of the Quality of Life (Minnesota Questionnaire (MHFLQ), Seattle Questionnaire (SAQ), SF-36 Questionnaire). Estimation of Efficiency.

  At baseline and after one year.

• Assessment of the Functional Class of Exertional Angina at 12 Months After Surgical Treatment.

  up to 12 months

• Dynamics of the Functional Class of Heart Failure (NYHA). Estimation of Efficiency.

  Assessment of the dynamics at 12 months after treatment.

• Evaluation of the Left Ventricular Ejection Fraction 12 Months After Treatment.

  12 months after treatment.

Other Outcomes (3)

• The Volume of Cellular Material (Cytosis).

  Initial data at the time of collection of bone marrow cells.

• The Amount of Cell Material (Percentage).

  Initial data at the time of collection of bone marrow cells.

• Smoking as a Factor That Negatively Affects the Results of the Test With a 6-minute Walk in Dynamics.

  12 months after treatment.

Study Arms (3)

Group 1

ACTIVE COMPARATOR

Intramyocardial administration of autologous bone marrow mononuclear cells during the operation coronary artery bypass grafting 0.2 ml - 10 injection in the zone of blood supply LAD.

Procedure: Group 1

Group 0

PLACEBO COMPARATOR

Intramyocardial administration of 0.9 % NaCl (sodium chloride) 0.2 ml - 10 injection in the zone of blood supply LAD during the operation coronary artery bypass grafting.

Procedure: Group 0

Group 2

ACTIVE COMPARATOR

Intramyocardial and intracoronary administration of autologous bone marrow mononuclear cells during coronary artery bypass grafting intramyocardial 0.2 ml - 10 injection in the zone of blood supply LAD.

Procedure: Group 2

Interventions

Group 1 PROCEDURE

Coronary artery bypass grafting with intramyocardial administration of autologous bone marrow mononuclear cells 0.2 ml - 10 injection in the zone of blood supply LAD.

Also known as: CABG with intramyocardial administration of ABMMC.

Group 1

Group 0 PROCEDURE

Coronary artery bypass grafting with intramyocardial administration of 0.9 % NaCl (sodium chloride) 0.2 ml - 10 injection in the zone of blood supply LAD.

Also known as: CABG with administration of 0.9 % sodium chlorid.

Group 0

Group 2 PROCEDURE

Coronary artery bypass grafting with intramyocardial and intracoronary administration of autologous bone marrow mononuclear cells intramyocardial administration 0.2 ml - 10 injection in the zone of blood supply LAD.

Also known as: CABG with intramyocardial and intracoronary administration of ABMMC.

Group 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Location

Related Publications (2)

• 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

  BACKGROUND

• 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

  BACKGROUND

Related Links

• 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).
• 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.

MeSH Terms

Conditions

Myocardial Ischemia; Heart Failure, Diastolic; Reperfusion Injury; Heart Murmurs

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Failure; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Limitations and Caveats

No limitations identified.

Results Point of Contact

• Title: Vladimir V Komok, Ph.D
• Organization: First Pavlov State Medical University of St. Petersburg

vladimir_komok@mail.ru

8-904-632-19-00

Study Officials

• Vladimir V Komok, Ph.D

  First Pavlov State Medical University of St. Petersburg.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Randomization into three observation groups was carried out according to the table of random numbers.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 1, 2014
• First Posted: February 11, 2014
• Study Start: February 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2018
• Last Updated: May 24, 2021
• Results First Posted: May 24, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)