Ischemic Heart DiseaseTAMISNCT02059512

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

A study testing Group 1, Group 0 and Group 2 in people with Ischemic Heart Disease and Bone Marrow Cells, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Ischemic Heart Disease, Bone Marrow Cells, Coronary Artery Bypass Grafting (CABG)
What is being tested?: Group 1, Group 0 and Group 2
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 117 participants
Where: 1 siteRussia
Study dates: Feb 2013to Jan 2018
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

Russia1 site

First Pavlov State Medical University of St. Petersburg
Saint Petersburg, 197089

Other trials in Russia

About this study

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

Read the detailed description

Additional estimation of safety:

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

Estimation of efficiency:

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

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

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

Conditions: Ischemic Heart Disease, Bone Marrow Cells, Coronary Artery Bypass Grafting (CABG), Heart Failure, Diastolic
Being tested: Group 1, Group 0, Group 2
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
Medical subject headings: Myocardial Ischemia, Heart Failure, Diastolic, Reperfusion Injury, Heart Murmurs

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Group 1Procedure or surgery
Also called CABG with intramyocardial administration of ABMMC.
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.
Group 0Procedure or surgery
Also called CABG with administration of 0.9 % sodium chlorid.
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.
Group 2Procedure or surgery
Also called CABG with intramyocardial and intracoronary administration of ABMMC.
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.

Study groups in NCT02059512
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Procedure: Group 2

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Intraoperative data.
Cardiopulmonary Bypass Time.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: Upon completion of the main stage of surgery.

Secondary outcomes (13)

All-cause Mortality Associated With the Progression of Basic Disease.
The total number of deaths - in the primary hospitalization and during the observation period of 12 months after surgical treatment - deaths associated with the progression of the initial disease.
The complication rate for CABG operations is 30±10%. According to n1=kn2; n1 sample size, in the control. In group 0, k=2/3 times more than in group 1 and group 2. The difference between the test and control frequencies is ε=p1-p2. Accordingly, with p1 = 0.2; p2=0.4, δ= 0.1; n1=49.5, n2=33. The result is group 0 - 36, group 1 and 2 - 25+25 = 50. The null hypothesis of complication rate δ.All patients included in the study.
Measured: 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.
The SF-36 questionnaire. The indicators of each scale vary between 0 and 100, where 100 represents total health. The results are presented in the form of scores on 8 scales, compiled in such a way that a higher score indicates a higher level of quality of life.MHFLQ - for patients with heart failure.The specified questionnaire consists of 21 questions. To answer each question, a scale of 6 points from the minimum intensity of certain symptoms to the maximum is used. The assessment is based on the sum of points, where the maximum number of points - 105 corresponds to the patient's worst condition. The lowest score 0 points is the best clinical condition of the patient. SAQ consists of 19 questions about the patient's condition, which are divided into the following 5 scales. The quality of life for each of the five scales under consideration is measured in percent, with 0% corresponding to the worst quality of life, and 100% to the best.
Measured: At baseline and after one year.
Assessment of the Functional Class of Exertional Angina at 12 Months After Surgical Treatment.
1. functional class - The usual load does not cause changes in the state of health. Painful attacks occur against the background of excessive loads - after climbing several flights of stairs, while walking fast.
2. functional class - Pain attacks when walking more than 500 meters, when climbing stairs more than one floor.
3. functional class - The patient does not tolerate minimal physical activity. An attack occurs when walking a distance of 50-100 meters. Climbing stairs is difficult.
4. functional class - Activity is significantly limited. Angina pectoris manifests itself when performing minimal actions, including at rest.
Measured: up to 12 months
Dynamics of the Functional Class of Heart Failure (NYHA). Estimation of Efficiency.
1. functional class - There is no limitation of a person's physical activity, shortness of breath manifests itself when going above the third floor.
2. functional class - slight limitation of activity, palpitations, shortness of breath, fatigue occur during normal physical activity and more.
3. functional class - Symptoms occur with the smallest physical activity, resulting in a significant decrease in activity. At rest, clinical manifestations are not observed.
The smaller the functional class, the better the quality of human life.
Measured: Assessment of the dynamics at 12 months after treatment.
Evaluation of the Left Ventricular Ejection Fraction 12 Months After Treatment.
According to echocardiography.
Measured: 12 months after treatment.
Estimation of the Index of Linear Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
Evaluation of myocardial contractility according to echocardiography, in particular the size of the left ventricle - the index was carried out 12 months after CABG. The higher the indicator (left ventricular size - index), the worse the prognosis of an unfavorable 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 - size of the left ventricle (mm.)/ body mass index (kg/m^2).
Measured: 12 months after the treatment.
Estimation of the Index of Volumetric Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
Evaluation of myocardial contractility according to echocardiography, in particular the volume of the left ventricle - the index was carried out 12 months after CABG. The higher the indicator (left ventricular volume - index), the worse the prognosis of an unfavorable 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 (mm.)/ body mass index (kg/m^2).
Measured: 12 Months After the Treatment
Assessment of Left Ventricular Diastolic Function - Peak E of Transmitral Flow and Peak А of Transmitral Flow 12 Months After Treatment.
Evaluation of left ventricular diastolic function (echocardiography). The peak velocity E reflects the pressure gradient between the LA and LV in early diastole, and it is affected by preload and disturbance LV relaxation The speed of peak A, which forms at the end diastole, influences LV compliance and contractility left atrium.
Measured: 12 months after treatment.
Assessment of Left Ventricular Diastolic Function E/A - 12 Months After Treatment.
The ratio of the transmitral flow, wave E (ejection wave / left ventricular contraction) to wave A (ejection wave / left atrial contraction). The norm is 0.75-1.5 Less than 0.75 violation of relaxation, more than 1.5 restrictive type of diastolic dysfunction.
Measured: 12 months after treatment
Assessment of Left Ventricular Diastolic Function - DT and IVRT 12 Months After Treatment.
Echocardiographic data ( DT (Half-time of wave E), time of isovolumic relaxation of the left ventricle (IVRT).
DT (Half-time of wave E). The DT time index reflects the relaxation process LV, LV diastolic pressure after mitral valve opening, and LV compliance. 150-200 ms - normal; > 200 ms - violation of relaxation; 150-200 ms - pseudonormal type of left ventricular filling; <150 ms - restrictive type of diastolic dysfunction IVRT (time of isovolumic relaxation of the left ventricl.) <100 ms - normal; > 100 ms - violation of relaxation
Measured: 12 Months After Treatment.
Distance Traveled in the 6-minute Walk Test. Test Results With 6 Minute Walk
The dynamic of the number of meters walked according to the 6-minutes walk test (6MWD) in the observation groups.
Measured: initially and after 12 months
The Number of Functioning Grafts 12 Months After CABG. Patency of Grafts Within a Specified Time of Treatment (Angiography).
According to the angiographic study.
Measured: up to 12 months
Analysis of the Effect of Left Ventricular Diastolic Dysfunction on the Patency of the Grafts.
Echocardiographic data.
Measured: up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2013Jan 2018

First posted11 Feb 2014 (estimated)
Study startFeb 2013
Primary completionDec 2016
Study completionJan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Ischemic Heart DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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.
Masking: Single blind
Who is masked: Investigator
Enrolment: 117 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02059512
Sponsor's protocol ID: NBK-2901-AMNKM
Acronym: TAMIS
Status last verified: May 2021
First submitted: 1 Feb 2014
Last updated: 24 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02059512
Acronym / sponsor ID: TAMIS / NBK-2901-AMNKM
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
Study type: Interventional
Recruitment status: Completed
Enrolment: 117 participants (actual)
Lead sponsor: St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
Study start: Feb 2013 (actual)
Primary completion: Dec 2016 (actual)
Study completion: Jan 2018 (actual)
First posted: 11 Feb 2014 (estimated)
Results: Posted 24 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Additional estimation of safety:

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

Estimation of efficiency:

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

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

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 3
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.

Arm	Type	Receives
Group 1	Active comparator	Procedure: Group 1Intramyocardial 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.
Group 0	Placebo comparator	Procedure: Group 0Intramyocardial 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.
Group 2	Active comparator	Procedure: Group 2Intramyocardial 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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Group 1Also: CABG with intramyocardial administration of ABMMC.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.	Procedure or surgery	Group 1
Group 0Also: CABG with administration of 0.9 % sodium chlorid.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.	Procedure or surgery	Group 0
Group 2Also: CABG with intramyocardial and intracoronary administration of ABMMC.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.	Procedure or surgery	Group 2

Primary outcome

Assessment of the Initial Risk of Surgery (EuroScore II).
Time frame: Before CABG surgery at baseline.
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.
Length of Hospital Stay. Length of Stay in the Intensive Care Unit.
Time frame: Primary hospitalization for planned CABG.
The results were obtained from the analysis of primary data.
The Severity of the Systemic Inflammatory Response in the Postoperative Period (Leukocytosis).
Time frame: 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 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.
Assessment of the Degree of General Inflammatory Response (C-reactive Protein (CRP)),
Time frame: 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.
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.
The Volume of Discharge Through the Drains in the Early Postoperative Period.
Time frame: Evaluation of these data - for the time spent in the intensive care unit before removing the drains.
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.
Dynamics of Markers of Myocardial Damage (Troponin I, Myoglobin).
Time frame: 1 and 3 days of the postoperative period.
Assessment of the severity of the period of ischemia / reperfusion. And the effect of autologous bone marrow mononuclear cells transplantation on these indicators.
Dynamics of Markers of Myocardial Damage (Creatine Phosphokinase Fraction MB (CPK-MB)).
Time frame: 1 and 3 days of the postoperative period.
Assessment of the severity of the period of ischemia / reperfusion. And the effect of autologous bone marrow mononuclear cells transplantation on these indicators.
Intraoperative Assessment of Homeostasis (Hemoglobin (Hb).
Time frame: Intraoperative data.
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 Assessment of Homeostasis (Hematocrit (HCT)).
Time frame: Intraoperative data.
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 Assessment of Homeostasis (К+).
Time frame: Intraoperative data.
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.
Cardiopulmonary Bypass Time.
Time frame: Intraoperative data.
Time of Aortic Clamping (Anoxia).
Time frame: Intraoperative data.
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.
Assessment of Complications in the Postoperative Period. Additional Estimation of Safety.
Time frame: Postoperative period.
The presence of complications in the postoperative period (Hydrothorax, Hydropericardium, Cardiac arrhythmias - atrial fibrillation / atrial flutter).
Left Ventricular Ejection Fraction - Echocardiography - Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.
Time frame: 7-14 days of the postoperative period
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.
Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment - Echocardiography (Size of the Left Ventricle - Index). Additional Estimation of Safety.
Time frame: 7-14 days after surgery
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).
Volume of the Left Ventricle - Index - Echocardiography. Assessment of Myocardial Contractility on Days 7-14 After Surgical Treatment. Additional Estimation of Safety.
Time frame: 7-14 days after surgery
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).
Restoration of the Heart Rate After the Completion of the Main Stage of the Surgical Intervention. Additional Estimation of Safety.
Time frame: Upon completion of the main stage of surgery.
The need to perform defibrillation to restore sinus rhythm, at the end of the main stage of surgery.

13 secondary outcomes

All-cause Mortality Associated With the Progression of Basic Disease.
Time frame: 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.
Time frame: At baseline and after one year.
Assessment of the Functional Class of Exertional Angina at 12 Months After Surgical Treatment.
Time frame: up to 12 months
Dynamics of the Functional Class of Heart Failure (NYHA). Estimation of Efficiency.
Time frame: Assessment of the dynamics at 12 months after treatment.
Evaluation of the Left Ventricular Ejection Fraction 12 Months After Treatment.
Time frame: 12 months after treatment.
Estimation of the Index of Linear Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
Time frame: 12 months after the treatment.
Estimation of the Index of Volumetric Parameters of the Left Ventricle 12 Months After the Treatment. Estimation of Efficiency.
Time frame: 12 Months After the Treatment
Assessment of Left Ventricular Diastolic Function - Peak E of Transmitral Flow and Peak А of Transmitral Flow 12 Months After Treatment.
Time frame: 12 months after treatment.
Assessment of Left Ventricular Diastolic Function E/A - 12 Months After Treatment.
Time frame: 12 months after treatment
Assessment of Left Ventricular Diastolic Function - DT and IVRT 12 Months After Treatment.
Time frame: 12 Months After Treatment.
Distance Traveled in the 6-minute Walk Test. Test Results With 6 Minute Walk
Time frame: initially and after 12 months
The Number of Functioning Grafts 12 Months After CABG. Patency of Grafts Within a Specified Time of Treatment (Angiography).
Time frame: up to 12 months
Analysis of the Effect of Left Ventricular Diastolic Dysfunction on the Patency of the Grafts.
Time frame: up to 12 months

Results and safety

Results posted to the registry on 24 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Intramyocardial Administration 0.9 % NaCl (Sodium Chloride) - Group 0	46	37
Intramyocardial Administration Autologous Bone Marrow Stem Cells - Group 1	34	25
Intramyocardial and Intracoronary Administration Autologous Bone Marrow Stem Cells - Group 2	37	23

Primary outcome: Assessment of the Initial Risk of Surgery (EuroScore II).

Time frame: Before CABG surgery at baseline.. Mean (Standard Deviation). Unit: percent

Measure	Group 0 n = 37	Group 1 n = 25	Group 2 n = 23
Value	1.3 (0.68)	1.07 (0.47)	1.02 (0.4)

Group 0 vs Group 1 vs Group 2: p = 0.24, Kruskal-Wallis

Population analysed: The data of all patients initially included in the study were analyzed.

Primary outcome: Length of Hospital Stay. Length of Stay in the Intensive Care Unit.

Time frame: Primary hospitalization for planned CABG.. Mean (Standard Deviation). Unit: days

Measure	Group 0 n = 37	Group 1 n = 25	Group 2 n = 23
Hospital Stay	36.8 (11.2)	32.8 (13.9)	38.4 (15.2)
Days in the intensive care unite	3.9 (2.2)	3.1 (1.7)	3.3 (1.8)

Group 0 vs Group 1 vs Group 2: p = 0.1, Kruskal-Wallis
Group 0 vs Group 1 vs Group 2: p = 0.1, Kruskal-Wallis

Population analysed: The data of all patients initially included in the study were analyzed.

Primary outcome: The Severity of the Systemic Inflammatory Response in the Postoperative Period (Leukocytosis).

Time frame: 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.. Mean (Standard Deviation). Unit: x10^9 cells/L"

Measure	Group 0 n = 37	Group 1 n = 25	Group 2 n = 23
Leu (leukocytes) / initially	8.3 (2.2)	6.5 (1.5)	7.3 (2.04)
Leu / in the postoperative period - an interval of 0-6 hours	13.9 (6.3)	14.1 (1.9)	16.2 (5.4)
Leu / in the postoperative period - an interval of 12-18 hours	13.9 (3.99)	14.7 (5.9)	13.3 (3.7)
Leu / in the postoperative period - an interval of 18-24 hours	13.08 (2.4)	15.4 (2.4)	16.99 (3.9)
Leu / in the postoperative period 48 hours	13.8 (5.5)	14.8 (2.2)	13.3 (3.97)
Leu / in the postoperative period 72 hours	11.3 (4.1)	9.4 (1.6)	11.4 (1.9)
Leu / in the postoperative period 96 hours	10.1 (2.7)	8.7 (2.6)	10.4 (1.99)
Leu / in the postoperative period 7 days	11.9 (5.9)	9.5 (2.3)	10.4 (3.2)

Group 0 vs Group 1 vs Group 2: p = 0.4, Kruskal-Wallis
Group 0 vs Group 1 vs Group 2: p = 0.8, Kruskal-Wallis
Group 0 vs Group 1 vs Group 2: p = 0.9, Kruskal-Wallis

Population analysed: The data of all patients initially included in the study were analyzed.

Primary outcome: Assessment of the Degree of General Inflammatory Response (C-reactive Protein (CRP)),

Time frame: 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.. Mean (Standard Deviation). Unit: mg/l

Measure	Group 0 n = 37	Group 1 n = 25	Group 2 n = 23
CRP initially/ mg / l	4.4 (6.05)	3.05 (2)	5.1 (5.1)
CRP control point in the interval 4-6 days of the postoperative period/ mg/l	80.2 (38)	85.9 (51.8)	121.1 (76.3)
CRP control point in the interval 12-14 days of the postoperative period/ mg/l	24.6 (13.8)	25.9 (20.9)	24.4 (15.6)

Group 0 vs Group 1 vs Group 2: p = 0.1, Kruskal-Wallis
Group 0 vs Group 1 vs Group 2: p = 0.4, Kruskal-Wallis
Group 0 vs Group 1 vs Group 2: p = 0.99, Kruskal-Wallis

Population analysed: The data of all patients initially included in the study were analyzed.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months after treatment. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 0	0 of 37 (0%)	0 of 37 (0%)	0 of 37
Group 1	0 of 25 (0%)	0 of 25 (0%)	0 of 25
Group 2	0 of 23 (0%)	0 of 23 (0%)	0 of 23

Limitations and caveats (from the sponsor): No limitations identified.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundKomok 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
BackgroundKomok 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
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).Link provided by the sponsor.
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.Link provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vladimir V Komok, Ph.D principal investigator

First Pavlov State Medical University of St. Petersburg.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Group 1, Group 0 and Group 2 in people with Ischemic Heart Disease and Bone Marrow Cells, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of the Initial Risk of Surgery (EuroScore II). (time frame: Before CABG surgery at baseline.). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02059512, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2021.