The Effects of oXiris in Cardiogenic Shock Requiring VA-ECMO (CLEAN ECMO)

The Effects of extraCorporeal bLood Purification (oXiris ®) in patiEnts With cArdiogeNic Shock Requiring VA-ECMO: A Prospective, Open-label, Randomized Controlled Pilot Study

Cardiogenic shock (CS) defines a state of systemic hypo-perfusion leading to end-organ dysfunction related to cardiac pump failure and with mortality rates in the range of 27-50% according to recent reviews. Patients with CS often received mechanical circulatory support, and venoarterial extracorporeal membrane oxygenator (V-A ECMO) is an effective tool to support refractory CS while ensuring continuous organ perfusion. Patients with CS present clinical signs of systemic inflammation and elevated plasma levels of prototypical inflammatory and vasoactive mediators, including C-reactive protein (CRP), Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα). As data is scarce in this field, we decided to perform a prospective randomized controlled pilot study to investigate the efficacy of extracorporeal cytokine and lipopolysaccharide adsorption using Oxiris on humoral inflammation parameters, hemodynamics, and clinical outcomes in patients with CS requiring VA ECMO.

Study Overview

• Status: Completed
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Device: oXiris membrane; Diagnostic test: Blood tests

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with more than 18 years old

2. CS is defined as the presence of the following:

   2-1) Systolic blood pressure is less than 90 mmHg for more than 30 minutes despite the fluid therapy, or the use of pressure boosting agents to maintain the systolic blood pressure more than 90 mmHg.

   2-2) Peripheral hypoperfusion (cold skin, urine less than 30 cc per hour, impaired consciousness, lactate ≥2.0 mmol/l) or a person with pulmonary edema.

   2-3) Causes of CS include ischemic (acute myocardial infarction or ischemic cardiomyopathy, shock during percutaneous coronary intervention), myocardial (end-stage heart failure, myocarditis), post-cardiotomy shock, cardiac tamponade, or pulmonary thromboembolism.

3. Patients receiving VA ECMO owing related to the causes listed in 2-1, 2-2, 2-3.
4. Written informed consent from patient or legal surrogates

Exclusion Criteria:

1. Other causes except for CS: septic shock, cardiac arrest by serious ventricular arrhythmia mot related to the myocardial ischemia or heart failure.
2. Shock with unwitnessed cardiac arrest outside the hospital
3. Severe non-cardiac morbidity with expected survival less than 6 months (malignancy, respiratory failure)
4. Suspicious of brain death
5. Those who refused active treatment
6. Body weight under 30 kg
7. Heparin allergy
8. Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Oxiris for 24 h	Device: oXiris membrane; oXiris membrane for 24h; Diagnostic test: Blood tests; Blood tests just after randomization (0 h) and at 24 h, 48 h and 7 days
Active Comparator: Control; Usual care	Diagnostic test: Blood tests; Blood tests just after randomization (0 h) and at 24 h, 48 h and 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endotoxin level at 48 h	Plasma endotoxin level	48 hours after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vasoactive-Inotrope score	VIS = dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10,000 × vasopressin (units/kg/min) + 50 × levosimendan (µg/kg/min)	baseline, 24 hours, 48 hours, 72 hours, 96 hours, Day 7
Sequential Organ Failure Assessment score	determine rate of organ failure (higher scores mean a worse outcome)	baseline, 24 hours, 48 hours, 72 hours, 96 hours, Day 7
Plasma cytokines	IL-6, IL-4, IL-10, TNF-α, IL-1β/IL-1F2, CCL2/JE/MCP-1, IFN-gamma, IL-8/CXCL8	baseline, 24 hours, 48 hours, Day 7
GDF-15, angiopoietin-2	endothelial dysfunction	baseline, 24 hours, 48 hours, Day 7
Hospital mortality	death	at hospital discharge, through study completion, an average 2 months
Neurologic outcome	Cerebral Performance Catergories scale	at hospital discharge, through study completion, an average 2 months

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Jeong Hoon Yang, MD, PhD, Department of Critical Care Medicine, Samsung Medical Center, Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2022
• Primary Completion (Actual): January 8, 2024
• Study Completion (Actual): January 8, 2024

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cardiogenic shock; cytokine; endotoxin; venoarterial extracorporeal membrane oxygenation; oXiris
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: CLEAN ECMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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