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

Sepsis Clinical Trial

— OST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05042622
• Other study ID #: version 1.1
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2021
• Source: National Research Center for Cardiac Surgery, Kazakhstan
• Contact: Rymbay Kaliyev, MD
• Phone: +77055965060
• Email: rymbay[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Sepsis
• Septic Shock

Intervention

Device:
• Cytokine adsorber filter
• Intervention group #1 a cytokine adsorber will be used (30 patients): patients on ECMO - subgroup A; septic patients - subgroup B.
• Extracorporeal hemoperfusion cartridge
• Intervention group #2 an extracorporeal hemoperfusion cartridge will be used (30 patients): patients on ECMO - subgroup C, septic patients - subgroup D.

Locations

Country	Name	City	State
Kazakhstan	National Research Center for Cardiac Surgery	Astana

Sponsors (2)

Lead Sponsor	Collaborator
National Research Center for Cardiac Surgery, Kazakhstan	Ministry of Education and Science, Republic of Kazakhstan

Country where clinical trial is conducted

Kazakhstan, 

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* Note: There are 44 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Days on intensive care unit (ICU)	Days on intensive care unit (ICU)	30 days
Other	Vasopressor dosage	Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h	24, 48, 72 hours
Other	Fluid substitution and fluid balance	Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h	24, 48, 72 hours
Other	Length of hospital stay	Days at hospital	up to 1 months
Other	Mortality	The period of occurrence of mortality	First 72 hours
Primary	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
Primary	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- ainterleukin-8, interleukin-10, Tumor Necrosis Factor- a at 24, 48 hours.	24-48 hours of septic shock
Secondary	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
Secondary	Ventilator free days (VFD) - ECMO patients	ventilator days. VFD=0, if the patient dies in the first 30 days after randomization	30 days
Secondary	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
Secondary	Difference of d-dimers - ECMO patients	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Secondary	Difference of Serum lactate - ECMO patients	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Secondary	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
Secondary	serious adverse device effects - ECMO patients	serious complications or malfunctions related to the CytoSorb device	30 days
Secondary	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
Secondary	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
Secondary	adverse event of special interest: bleeding complications - ECMO patients	major bleeding events	30 days
Secondary	Difference of serum interleukin-6 level - Patients with septic shock	Comparison to enrollment or between 3 groups at 48, 72 h	48, 72 hours
Secondary	Difference of serum interleukin-1ß level - Patients with septic shock	Comparison to enrollment or between 3 groups at 24, 48, 72 h	24, 48, 72 hours
Secondary	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
Secondary	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