Innovative Technologies for the Treatment of Pulmonary and Heart Failure

Study Overview
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Brief Summary
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The purpose of the program. Formulation of new treatments for heart and pulmonary failure through using organ-replacing technologies. Formulation of a clinical protocol and implementation of treatment methods into clinical practice heart and pulmonary failure using organ-replacing technologies. New methods were created for rehabilitating the function of affected organs after implantation of the LVAD, a total artificial heart, an extracorporeal life-sustaining system will be of great importance, both for Kazakhstan and for states with similar problems of donor organ deficiency, will also improve the effectiveness of surgical treatment and reduce the level of complications and mortality of patients on the extracorporeal life-sustaining system and septic patients.

Detailed Description
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Objectives of the program. Task 1. Assessment of the results of the use of extracorporeal life support systems in the treatment of pulmonary and/or heart failure. Subtask 1.1. Assessment of the restoration of organ function during extracorporeal life support systems using extracorporeal hemocorrection. Subtask 1.2. Assessment of the normalization of the body's immune response and restoration of organ function during extracorporeal life support systems using an extracorporeal cytokine adsorber. Task 2. Studying the restoration of organ function during implantation of the left ventricular assist device as an organ-replacing aid in heart failure. Subtask 2.1. Assessment of the restoration of organ function during implantation of the left ventricular assist device with the use of extracorporeal hemocorrection. Subtask 2.2. Assessment of the normalization of the body's immune response and restoration of organ function upon implantation of the left ventricular assist device using an extracorporeal cytokine adsorber. Task 3. Studying the restoration of organ function during the implantation of the total artificial heart as an organ-replacing aid in case of heart failure. Task 3.1. Assessment of normalization of organ function restoration during implantation of the total artificial heart with the use of extracorporeal hemocorrection. Task 4. Studying the restoration of organ function during operations in conditions of the long-term cardiopulmonary bypass. Task 4.1. Assessment of the restoration of organ function during operations with long-term cardiopulmonary bypass, hypothermia, and circulatory arrest, with the use of extra corporeal hemocorrection. Task 4.2. Assessment of the restoration of organ function during operations with long-term cardiopulmonary bypass, hypothermia, and circulatory arrest using an extracorporeal cytokine adsorber. Task 5. Improvement of the method of implantation of organ-replacing technologies to reduce complications in the treatment of heart and pulmonary failure. Study design. Study type: interventional (clinical study) Set of participants: 100 participants Distribution: randomized Interventional model: parallel Masking: no Primary Goal: Treatment

Official Title
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Development of Innovative Technologies for the Treatment of Pulmonary and Heart Failure to Prolong Human's Life

Conditions
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Cardiogenic Shock, Ventricular Arrythmia, Cardiac Arrest With Successful Resuscitation, Sepsis, Multiple Organ Failure, Pulmonary Failure, Decompensated Heart Failure, Acute Heart Failure

Intervention / Treatment
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* Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection
* Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients on an extracorporeal life support system with heart failure: Implantation of intravenous ECMO Hemodynamic support with vasopressors and/or tonics; Procalcitonin level ≥ 1 ng/ml; Invasive hemodynamic monitoring; Written informed consent. Patients on an extracorporeal life support system with pulmonary failure: IV ECMO implantation High levels of venous and arterial CO2 (CO2> 50 mmHg), Low paO2, SvO2, SpO2. Invasive hemodynamic monitoring; Written informed consent. -Patients with left ventricular assistive device implantation: LVAD implantation Biventricular heart failure IV INTERMACS I-III Hemodynamic support with vasopressors and/or tonics; Procalcitonin level ≥ 0.1 ng/ml; Invasive hemodynamic monitoring; Written informed consent. -Patients in operations with prolonged artificial circulation, hypothermia and circulatory arrest: Hemodynamic support with vasopressors and/or tonics; Bypass duration> 120 minutes Hypothermia ≤ 25 0С Circulatory arrest Procalcitonin level ≥ 1 ng/ml; Invasive hemodynamic monitoring; Written informed consent. Exclusion Criteria: Patients on an extracorporeal life support system with heart failure: Age less than 18 years old Terminal hepatic or renal failure just before the procedure Patient's written refusal to participate in the study Patients on an extracorporeal life support system with pulmonary failure: Age less than 18 years old Terminal hepatic or renal failure just before the procedure Patient's written refusal to participate in the study Patients with left ventricular assistive device implantation: Age less than 18 years old Acute hepatic or renal failure just before the procedure Patient's written refusal to participate in the study Patients in operations with prolonged artificial circulation, hypothermia and circulatory arrest: Age less than 18 years old Terminal hepatic or renal failure just before the procedure Patient's written refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention team # 1 using an extracorporeal hemoperfusion device Jafron (Zhuhai Jafron Biomedical, China) (50 patients) in subgroups: A (n = 10) - patients on extracorporeal life support systems with heart failure; B (n = 10) - patients on extracorporeal life support systems with pulmonary failure; C (n = 5) - patients with implantation of a left ventricular accessory device; D (n = 25) - during operations with prolonged artificial circulation, hypothermia and circulatory arrest. Intervention team # 2 using extracorporeal cytokine, CytoSorb (CytoSorbents Corporation, Monmouth Junction, NJ, USA) (50 patients) in subgroups: A (n = 10) - patients on extracorporeal life support systems in heart failure; B (n = 10) - patients on extracorporeal life support systems with pulmonary failure; C (n = 5) - patients with implantation of a left ventricular accessory device; D (n = 25) - during operations with prolonged artificial circulation, hypothermia and circulatory arrest.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention team (1/1 group)<br>An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for heart failure... (10 patients) | Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection<br>* HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection, which is based on the removal of cytokines from whole blood by sorption on a special hemoadsorbent due to the peculiarities of its porous structure and inner surface, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (1/2 group)<br>An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for pulmonary failure (10 patients). | Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection<br>* HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection, which is based on the removal of cytokines from whole blood by sorption on a special hemoadsorbent due to the peculiarities of its porous structure and inner surface, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (1/3 group)<br>An extracorporeal hemoperfusion device will be installed in patients before/during the implantation of a left ventricular accessory (5 patients). | Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection<br>* HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection, which is based on the removal of cytokines from whole blood by sorption on a special hemoadsorbent due to the peculiarities of its porous structure and inner surface, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (1/4 group)<br>An extracorporeal hemoperfusion device will be installed in patients during operations with prolonged artificial circulation, hypothermia, and circulatory arrest. (25 patients). | Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection<br>* HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection, which is based on the removal of cytokines from whole blood by sorption on a special hemoadsorbent due to the peculiarities of its porous structure and inner surface, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (2/1 groups)<br>An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for heart failure. (10 patients) | Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber<br>* CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber is a biocompatible polymer with high adsorption capacity, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (2/2 groups)<br>An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for pulmonary failure. (10 patients) | Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber<br>* CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber is a biocompatible polymer with high adsorption capacity, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (2/3 groups)<br>An extracorporeal hemoperfusion device will be installed in patients before/during the implantation of a left ventricular accessory (5 patients) | Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber<br>* CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber is a biocompatible polymer with high adsorption capacity, which is indicated in conditions where cytokine levels are extremely elevated<br>|
| Active Comparator: Intervention team (2/4 groups)<br>An extracorporeal hemoperfusion device will be installed in patients during operations with prolonged artificial circulation, hypothermia, and circulatory arrest. (25 patients) | Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber<br>* CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber is a biocompatible polymer with high adsorption capacity, which is indicated in conditions where cytokine levels are extremely elevated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracorporeal life support system with pulmonary and / or heart failure: Cytokine response | The level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, tumor alpha-factor) before the start, 2 hours after the start of ECMO support, when ECMO is turned off, 24 hours after ECMO is turned off. | 24-48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure: SOFA-Score | Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity) | 24, 48, 72 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure | Doses of vasopressors and / or inotropes (µg / h / kg bodyweight) | Time: first 72 hours | 
| Patients with left ventricular assist device implantation: Difference of Cytokine response | Level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alfa, procalcitonin) | 24-48 hours | 
| Patients with left ventricular assist device implantation:vasopressors and / or inotropes | Doses of vasopressors and / or inotropes (µg / h / kg bodyweight) | first 72 hours | 
| Patients with left ventricular assist device implantation:Renal function | creatinine level | first 72 hours | 
| Patients with left ventricular assist device implantation:Lactate level | Lactate level | first 72 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: Difference of Cytokine response | Level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alfa, procalcitonin, C-reactive protein) | 24-48 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: SOFA-Score | Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity) | 24, 48, 72 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:Difference of mean arterial pressure | Comparison of mean arterial pressure at 24, 48, 72 hours between between two interventions (CytoSorb and Jafron) | 24, 48, 72 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure: Difference of CVP | Comparison of CVP at 24, 48, 72 hours between between two interventions (CytoSorb and Jafron) | 24, 48, 72 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure: Serum lactate | Level of serum lactate at 24, 48, 72 h | 24, 48, 72 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:Days on ventilator, vasopressor and renal replacement therapy | Total days on ventilator, vasopressor and renal replacement therapy within 30 days post-surgery will be assessed | until day 30 post-surgery | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: Difference of mean arterial pressure | Comparison of mean arterial pressure at 24, 48, 72 hours between between two interventions (CytoSorb and Jafron) | 24, 48, 72 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: Difference of CVP | Comparison of mean arterial pressure at 24, 48, 72 hours between between two interventions (CytoSorb and Jafron) | 24, 48, 72 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: Level of Serum lactate | Comparison of mean arterial pressure at 24, 48, 72 hours between between two interventions (CytoSorb and Jafron) | 24, 48, 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracorporeal life support system with pulmonary and / or heart failure:The level of C-reactive protein (CRP) | The level of C-reactive protein (CRP) before the start of ECMO, 2 hours after the implantation of ECMO, during ECMO, 24 hours after ECMO explantation. | 24-48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure: Level of leukocyte | Level of leukocyte cells in the bloodstream at 24, 48 hours | 24-48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:Application and dosage of vasopressors | Incidence of application and level of dosage of vasopressors on days 2 and 3 after surgery | first 48 hours | 
| Patients with left ventricular assist device implantation: The level of C-reactive protein (CRP) | The level of C-reactive protein (CRP) before the start of the operation, 2 hours after the start of the operation, when the operation is turned off, 24 hours after the shutdown of the operation | 24-48 hours | 
| Patients with left ventricular assist device implantation: Application and dosage of vasopressors | Incidence of application and level of dosage of vasopressors on days 2 and 3 after surgery | first 48 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: The level of C-reactive protein (CRP) | The level of C-reactive protein (CRP) before the cardiopulmonary bypass 2 hours after the cardiopulmonary bypass, when the cardiopulmonary bypass is turned off, 24 hours after the cardiopulmonary bypass. | 24-48 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest:Leukocyte function | Leukocyte function: heterogeneity of the population of leukocyte cells in the bloodstream | first 48 hours | 
| For operations with prolonged artificial circulation, hypothermia and circulatory arrest: Application and dosage of vasopressors | Incidence of application and level of dosage of vasopressors on days 2 and 3 after surgery | first 48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:The level of leukocytes | The level of leukocytes before the start of ECMO, 2 hours after the implantation of ECMO, during ECMO, 24 hours after ECMO explantation | 24-48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:The level of procalcitonin | The level of procalcitonin before the start of ECMO, 2 hours after the implantation of ECMO, during ECMO, 24 hours after ECMO explantation. | 24-48 hours | 
| Extracorporeal life support system with pulmonary and / or heart failure:Application and dosage of inotropes | Incidence of application and level of dosage of inotropes on days 2 and 3 after surgery | first 48 hours | 
| Patients with left ventricular assist device implantation: The level of leukocytes | The level of leukocytes before the start of the operation, 2 hours after the start of the operation, when the operation is turned off, 24 hours after the shutdown of the operation | 24-48 hours | 
| Patients with left ventricular assist device implantation: The level of procalcitonin | The level of procalcitonin before the start of the operation, 2 hours after the start of the operation, when the operation is turned off, 24 hours after the shutdown of the operation | 24-48 hours | 
| Patients with left ventricular assist device implantation: Application and dosage of inotropes | Incidence of application and level of dosage of inotropes on days 2 and 3 after surgery | first 48 hours | 
| For operations with prolonged cardio pulmonary bypass, hypothermia and circulatory arrest: The level of leukocytes | The level of leukocytes before the cardiopulmonary bypass 2 hours after the cardiopulmonary bypass, when the cardiopulmonary bypass is turned off, 24 hours after the cardiopulmonary bypass. | 24-48 hours | 
| For operations with prolonged cardiopulmonary bypass, hypothermia, and circulatory arrest: The level of procalcitonin | The level of procalcitonin before the cardiopulmonary bypass 2 hours after the cardiopulmonary bypass, when the cardiopulmonary bypass is turned off, 24 hours after the cardiopulmonary bypass. | 24-48 hours | 
| For operations with prolonged cardiopulmonary bypass, hypothermia, and circulatory arrest: Application and dosage of inotropes | Incidence of application and level of dosage of inotropes on days 2 and 3 after surgery | first 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephrology, Anesthesiology, Cardiothoracic surgery, Perfusion, Efferentology