Innovative Technologies for the Treatment of Pulmonary and Heart Failure

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Multiple Organ Failure; Decompensated Heart Failure; Ventricular Arrythmia; Pulmonary Failure; Cardiogenic Shock; Acute Heart Failure; Cardiac Arrest With Successful Resuscitation
• Intervention / Treatment: Device: HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection; Device: CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuri Pya, PhD, MD; Phone Number: +77172272090; Email: rp.nrcsc@gmail.com
• Study Contact Backup: Name: Timur Lesbekov, MD; Phone Number: +77172703100; Email: lesbekovt@mail.ru

Study Locations

• Kazakhstan
  • Astana, Kazakhstan, 010000
    • Recruiting
    • National Research Center for Cardiac Surgery
    • Contact: Yuriy Pya, PhD, MD; Phone Number: +77172703100; Email: rp.nrcsc@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention team (1/1 group); 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; 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
Active Comparator: Intervention team (1/2 group); 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; 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
Active Comparator: Intervention team (1/3 group); 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; 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
Active Comparator: Intervention team (1/4 group); 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; 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
Active Comparator: Intervention team (2/1 groups); 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; 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
Active Comparator: Intervention team (2/2 groups); 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; 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
Active Comparator: Intervention team (2/3 groups); 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; 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
Active Comparator: Intervention team (2/4 groups); 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; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	Length of stay in the intensive care unit	first 48 hours
Length of hospital stay	Length of hospital stay	up to 1 month
30 day survival rate.	30 day survival rate.	30 day

Collaborators and Investigators

• Sponsor: National Research Center for Cardiac Surgery, Kazakhstan
• Collaborators: Ministry of Education and Science, Republic of Kazakhstan
• Investigators: Principal Investigator: Yuri Pya, PhD, MD, National research Center for Cardiac Surgery JSC

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Nephrology; Perfusion; Anesthesiology; Cardiothoracic surgery; Efferentology
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Shock; Myocardial Infarction; Infarction; Heart Failure; Shock, Cardiogenic; Multiple Organ Failure
• Other Study ID Numbers: version01; BR10965200 (Other Grant/Funding Number: Ministry of Education and Science RK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Yes: There is a plan to make IPD and related data dictionaries available.
• IPD Sharing Time Frame: from October 2021 year and will become available till December 2023 year.
• IPD Sharing Access Criteria: The resulting patient data will be strictly confidential with ensuring privacy through strictly limited access to data, de-identification of data and destruction after the end of the study.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No