Organ-substituting Technologies in the Treatment of Heart and Pulmonary Failure (OST)

Innovative Solutions to Organ-substituting Technologies in the Treatment of Heart and Pulmonary Failure

The implementation of this project will improve the effectiveness of surgical treatment and reduce the level of complications and mortality among patients with heart failure and heart failure in the terminal stage.

The goal of the study. Improvement of organ-substituting technologies in the treatment of heart and respiratory failure.

Objectives of the study. Objective 1. To study the restoration of organ function during implantation of extracorporeal membrane oxygenation (ECMO), as an organ replacement, in cardiac and / or respiratory failure.

Objective 2. To study the results of applying organ-substituting technologies in the treatment of sepsis.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Device: Cytokine adsorber filter; Device: Extracorporeal hemoperfusion cartridge

Detailed Description

The implementation of this project will improve the effectiveness of surgical treatment and reduce the level of complications and mortality among patients with heart failure and heart failure in the terminal stage.

2.2. The goal of the program. Improvement of organ-substituting technologies in the treatment of heart and respiratory failure.

2.3. Objectives of the program. Objective 1. To study the restoration of organ function during implantation of extracorporeal membrane oxygenation (ECMO), as an organ replacement, in cardiac and/or respiratory failure.

Subtask 1.1. Evaluation of the recovery of organ function during ECMO using extracorporal hemo correction procedure.

Subtask 1.2. Evaluation of the normalization of the organism's immune response and restoration of organ function when conducting ECMO using the extracorporeal cytokine adsorber.

Subtask 1.3. Evaluation of the normalization of the organism's immune response and restoration of organ function when conducting ECMO using the extracorporeal hemoperfusion cartridge.

Objective 2. To study the results of applying organ-substituting technologies in the treatment of sepsis.

Subtask 2.1. Assessment of the recovery of organ function in the application of extracorporal hemo correction in septic patients.

Subtask 2.2. Evaluation of the normalization of the organism immune response and restoration of organ function when using the extracorporeal cytokine adsorber in septic patients.

Subtask 2.3. Evaluation of the normalization of the organism's immune response and restoration of organ function when using the extracorporeal hemoperfusion cartridge.

In this study, will be developed methods to restore the function of affected organs after implantation of ECMO and patients with sepsis in combination with extracorporeal hem correction, which will improve the results of surgical treatment of patients with end-cardiac and respiratory failure.

New methods developed to restore the function of affected organs after implantation of mechanical support devices and patients with sepsis will be of great importance both for Kazakhstan and for countries with similar categories of patients, which will improve the efficiency of surgical treatment and reduce the level of complications and mortality.

Clinical research data will form the basis of practical protocols for extracorporeal membrane oxygenation (ECMO) and patients with sepsis, which will improve organ repair, reduce postoperative complications, improve quality of life and reduce mortality after surgery.

Research methods and ethical issues Patients before implantation of ECMO and/or patients with sepsis will be enrolled in the study after giving a written, signed informed consent.

The participants will be randomized into 3 groups:

• Intervention group #1 a cytokine adsorber will be used (30 patients): patients on ECMO - subgroup A; septic patients - subgroup B.
• Intervention group #2 an extracorporeal hemoperfusion cartridge will be used (30 patients): patients on ECMO - subgroup C, septic patients - subgroup D.
• Control group #3 without using extracorporeal adsorber (30 patients): patients on ECMO subgroup - E, septic patients - subgroup F.

The investigators will collect demographic, clinical, and laboratory data about patients before, during, and after the operation The incidence of early cellular or humoral rejection, length of ventilation, ICU and hospital stay, the use of vasopressors and inotropes in the perioperative period, and incidence of perioperative complications and survival will be documented.

The level of cytokines (IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alfa) and complements before, during, and after the use of ECMO, patients with sepsis will be determined if the investigators find the relevant differences between the two groups in clinical variables.

Study Design Study Type: Interventional (Clinical Trial) Estimated Enrollment: 90 Participants Allocation: randomized Interventional Model: Parallel assignment Masking: None (Open Label)

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rymbay Kaliyev, MD; Phone Number: +77055965060; Email: rymbay@mail.ru

Study Locations

• Kazakhstan
  • Astana, Kazakhstan, 010000
    • Recruiting
    • National Research Center for Cardiac Surgery
    • Contact: Timur Lesbekov, PhD, MD; Phone Number: +77019659151; Email: lesbekovt@mail.ru
    • Sub-Investigator: Rymbay Kaliyev, MD
    • Sub-Investigator: Aydyn Kuanyshbek, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-

ICU patients with ECMO:

• Hemodynamic support with vasopressors
• Procalcitonin level ≥ 1 ng/ml
• Invasive hemodynamic monitoring
• Written informed content

ICU patients with the septic shock of medical origin:

• Signs of hypoperfusion: serum lactate >2 mmol/L, low central venous oxygen saturation (ScvO2) (<70%) or high ScvO2 (>85%), metabolic acidosis, oligo-anuria, high venous-to-arterial CO2-gap (dCO2 >6 mm Hg)
• Hemodynamic support with vasopressors
• Procalcitonin level ≥ 1 ng/ml
• Invasive hemodynamic monitoring
• Written informed content

Exclusion Criteria:

• ICU patients with ECMO:

  • age < 18 years
  • acute liver or kidney failure straight before transplantation
  • the patient declines to participate in the study

ICU patients with the septic shock of medical origin:

• Patients under 18 years
• Pregnancy (bHCG test positivity)
• Surgical intervention in context with the septic insult New York Heart Association IV heart failure
• Acute coronary syndrome
• Acute hematological malignancies
• Immunosuppression, systemic steroid therapy (>10mg prednisolone/day)
• Human immunodeficiency virus infection (HIV) and active AIDS
• Patients with donated organs
• Thrombocytopenia (<20.000/ml)
• More than 10%-of body surface area with third-degree burn

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cytokine adsorber patients on ECMO; Cytokine adsorber filter will be installed into the (hemodialysis or cardiopulmonary bypass (CPB) (15 patients on ECMO)	Device: Cytokine adsorber filter; • Intervention group #1 a cytokine adsorber will be used (30 patients): patients on ECMO - subgroup A; septic patients - subgroup B.
EXPERIMENTAL: Cytokine adsorber patients with sepsis; Cytokine adsorber filter will be installed into the (hemodialysis or cardiopulmonary bypass (CPB) (15 patients with sepsis)	Device: Cytokine adsorber filter; • Intervention group #1 a cytokine adsorber will be used (30 patients): patients on ECMO - subgroup A; septic patients - subgroup B.
EXPERIMENTAL: Extracorporeal hemoperfusion cartridge patients on ECMO; Extracorporeal hemoperfusion cartridge will be installed into the (hemodialysis or cardiopulmonary bypass (CPB) (15 patients on ECMO)	Device: Extracorporeal hemoperfusion cartridge; • Intervention group #2 an extracorporeal hemoperfusion cartridge will be used (30 patients): patients on ECMO - subgroup C, septic patients - subgroup D.
EXPERIMENTAL: Extracorporeal hemoperfusion cartridge patients with sepsis; Extracorporeal hemoperfusion cartridge will be installed into the (hemodialysis or cardiopulmonary bypass (CPB) (15 patients with sepsis)	Device: Extracorporeal hemoperfusion cartridge; • Intervention group #2 an extracorporeal hemoperfusion cartridge will be used (30 patients): patients on ECMO - subgroup C, septic patients - subgroup D.
NO_INTERVENTION: Control (subgroups)1; No filter will be installed into the ECMO in this study group (15 patients)
NO_INTERVENTION: Control (subgroups) 2; No filter will be installed into the patient with sepsis (15 patients)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of Cytokine response - ECMO patients	Level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alfa) before initiation of ECMO, 2 hours after initiation ECMO support, at explantation of ECMO support, 6-12-24 hours after explantation of ECMO support.	6-24 hours
Difference of Cytokine response - Patients with septic shock	Level of procalcitonin, Level of C-reactive protein, Level of interleukin-1, Level of interleukin-6, Level of interleukin-8, Level of interleukin-10, Level of Tumor Necrosis Factor- αinterleukin-8, interleukin-10, Tumor Necrosis Factor- α at 24, 48 hours.	24-48 hours of septic shock

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event of special interest: blood-clotting in the ECMO system	unintended blood-clotting in the ECMO system during operation of the device	30 days
Inflammatory reaction - Patients with septic shock	Level of C reactive protein (CRP), white blood cells and procalcitonin immediately after induction of anesthesia, before initiation of adsorber, 2 hours after initiation of adsorber, at termination of adsorber, 6-12-24 hours after wean of adsorber.	6-24 hours
Ventilator free days (VFD) - ECMO patients	ventilator days. VFD=0, if the patient dies in the first 30 days after randomization	30 days
Time to extubation from ventilation and explantation from ECMO - ECMO patients	Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.	30 days
Difference of d-dimers - ECMO patients	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Difference of Serum lactate - ECMO patients	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
SOFA-Score - ECMO patients	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
serious adverse device effects - ECMO patients	serious complications or malfunctions related to the CytoSorb device	30 days
adverse event of special interest: air in the ECMO system - ECMO patients	unintended air in the ECMO system during operation of the device	30 days
adverse event of special interest: bleeding complications - ECMO patients	major bleeding events	30 days
Difference of serum interleukin-6 level - Patients with septic shock	Comparison to enrollment or between 3 groups at 48, 72 h	48, 72 hours
Difference of serum interleukin-1β level - Patients with septic shock	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Difference of serum interleukin-10 level - Patients with septic shock	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Difference of serum procalcitonin level - Patients with septic shock	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time	Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.	30 days
Days on intensive care unit (ICU)	Days on intensive care unit (ICU)	30 days
Vasopressor dosage	Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h	24, 48, 72 hours
Fluid substitution and fluid balance	Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h	24, 48, 72 hours
Length of hospital stay	Days at hospital	up to 1 months
Mortality	The period of occurrence of mortality	First 72 hours

Collaborators and Investigators

• Sponsor: National Research Center for Cardiac Surgery, Kazakhstan
• Collaborators: Ministry of Education and Science, Republic of Kazakhstan
• Investigators: Principal Investigator: Timur Lesbekov, 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): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (ACTUAL): September 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Heart failure; Sepsis; Extracorporeal membrane oxygenation; Organ-substituting technologies; Pulmonary failure; Adsorber
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: Version 1.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD
• IPD Sharing Time Frame: 01.01.2021 - 31.12.2023
• IPD Sharing Access Criteria: All patients will receive voluntary informed consent of the established sample with permission to use clinical data for scientific purposes. In addition, the study will be strictly controlled by researchers for the absence of plagiarism, falsification and fabrication of data in order to achieve the most ethical conduct of the study. The obtained patient data will be kept strictly confidential, ensuring privacy by strictly limited access to data, de-identification of data and destruction after the end of the study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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