Innovative Technologies for the Treatment of Pulmonary and Heart Failure

Not Applicable

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

• Registration Number: NCT05090930
• Lead Sponsor: National Research Center for Cardiac Surgery, Kazakhstan

Brief Summary

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

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 Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2021-09-09
• Status Verified: 2021-10
• Study First Submitted QC: 2021-10-11
• Last Update Submitted: 2021-10-11
• Study First Posted: 2021-10-25
• Last Update Posted: 2021-10-25
• Primary Completion: 2023-07-01
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention team (1/3 group)	HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection	An extracorporeal hemoperfusion device will be installed in patients before/during the implantation of a left ventricular accessory (5 patients).
Intervention team (1/1 group)	HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection	An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for heart failure... (10 patients)
Intervention team (1/2 group)	HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection	An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for pulmonary failure (10 patients).
Intervention team (2/2 groups)	CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber	An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for pulmonary failure. (10 patients)
Intervention team (1/4 group)	HA330 - Jafron Biomedical Co., Ltd., China - extracorporeal hemocorrection	An extracorporeal hemoperfusion device will be installed in patients during operations with prolonged artificial circulation, hypothermia, and circulatory arrest. (25 patients).
Intervention team (2/1 groups)	CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber	An extracorporeal hemoperfusion device will be installed in the device of the extracorporeal life support system for heart failure. (10 patients)
Intervention team (2/4 groups)	CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber	An extracorporeal hemoperfusion device will be installed in patients during operations with prolonged artificial circulation, hypothermia, and circulatory arrest. (25 patients)
Intervention team (2/3 groups)	CytoSorb (CytoSorbents Corp., USA) - an extracorporeal cytokine adsorber	An extracorporeal hemoperfusion device will be installed in patients before/during the implantation of a left ventricular accessory (5 patients)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

National Research Center For Cardiac Surgery; 🇰🇿 Astana, Kazakhstan