Clinical trial NCT05042622: Organ-substituting Technologies in the Treatment of Heart and Pulmonary Failure
Official title: Innovative Solutions to Organ-substituting Technologies in the Treatment of Heart and Pulmonary Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Septic Shock
Sepsis
Keywords: Organ-substituting technologies
Heart failure
Pulmonary failure
Sepsis
Extracorporeal membrane oxygenation
Adsorber
Lead sponsor: National Research Center for Cardiac Surgery, Kazakhstan
Sponsor class: OTHER
Collaborators: name: Ministry of Education and Science, Republic of Kazakhstan
First posted: 2021-09-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study Design Study Type: Interventional (Clinical Trial) Estimated Enrollment: 90 Participants Allocation: randomized Interventional Model: Parallel assignment Masking: None (Open Label)
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Difference of Cytokine response - ECMO patients
timeFrame: 6-24 hours
measure: Difference of Cytokine response - Patients with septic shock
timeFrame: 24-48 hours of septic shock
Secondary outcomes:
measure: Inflammatory reaction - Patients with septic shock
timeFrame: 6-24 hours
measure: Ventilator free days (VFD) - ECMO patients
timeFrame: 30 days
measure: Time to extubation from ventilation and explantation from ECMO - ECMO patients
timeFrame: 30 days
measure: Difference of d-dimers - ECMO patients
timeFrame: 24, 48, 72 hours
measure: Difference of Serum lactate - ECMO patients
timeFrame: 24, 48, 72 hours
measure: SOFA-Score - ECMO patients
timeFrame: 24, 48, 72 hours
measure: serious adverse device effects - ECMO patients
timeFrame: 30 days
measure: adverse event of special interest: air in the ECMO system - ECMO patients
timeFrame: 30 days
measure: adverse event of special interest: blood-clotting in the ECMO system
timeFrame: 30 days
measure: adverse event of special interest: bleeding complications - ECMO patients
timeFrame: 30 days
measure: Difference of serum interleukin-6 level - Patients with septic shock
timeFrame: 48, 72 hours
measure: Difference of serum interleukin-1β level - Patients with septic shock
timeFrame: 24, 48, 72 hours
measure: Difference of serum interleukin-10 level - Patients with septic shock
timeFrame: 24, 48, 72 hours
measure: Difference of serum procalcitonin level - Patients with septic shock
timeFrame: 24, 48, 72 hours
Other outcomes:
measure: Overall survival time
timeFrame: 30 days
measure: Days on intensive care unit (ICU)
timeFrame: 30 days
measure: Vasopressor dosage
timeFrame: 24, 48, 72 hours
measure: Fluid substitution and fluid balance
timeFrame: 24, 48, 72 hours
measure: Length of hospital stay
timeFrame: up to 1 months
measure: Mortality
timeFrame: First 72 hours
Locations:
city: Astana
country: Kazakhstan
facility: National Research Center for Cardiac Surgery
Study officials:
affiliation: National research Center for Cardiac Surgery JSC
name: Timur Lesbekov, PhD, MD
role: PRINCIPAL_INVESTIGATOR
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