Cerebral Bleeding in COVID-19 ARDS Patients on Veno-venous ECMO

Study Overview
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Brief Summary
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Critically ill patients with severe acute respiratory distress syndrome (ARDS) sometimes require treatment with veno-venous extracorporeal membrane oxygenation (ECMO) to support gas exchange. To prevent clotting of the ECMO circuit, these patients need to be anticoagulated. This protective anticoagulation also leeds to an increased bleeding risk. Most critically ill COVID-19 patients suffer from an ARDS and some require ECMO support. However, the optimal strategy and targets for the anticoagulation of these patients remain uncertain. Studies have shown that COVID-19 is associated with endotheliopathy probably leading to procoagulatory effects. On the other hand, the incidence of bleeding complications associated with this endotheliopathy is not clear and remains to be elucidated. Anticoagulation of COVID-19 patients on ECMO thus poses a challenge for clinicians. The hypothesis of the current project is that COVID-19 patients with ARDS on ECMO exhibit a higher number of bleeding complications compared to historical control patients with non-COVID-19 ARDS requiring ECMO support.

Detailed Description
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The primary aim of the project is to retrospectively analyze the incidence of bleeding complications (especially cerebral bleedings) in critically ill COVID-19 patients with ARDS requiring ECMO support. The incidences of bleeding will be compared with a historical control cohort of non-COVID-19 patients on ECMO support. The data analysis will be set up within a multicentric, retrospective study involving the University Hospital Zurich (Switzerland), the Medical School Hannover (Germany) and the University Hospital Bonn (Germany). The aim of the multicentric approach is to increase the case load and to improve the validity of the data, which could possibly have therapeutic implications in the future. Aside from demographic and baseline date, mortality and causes of death, comorbidities, the anticoagulation strategy (substance, targets of anticoagulation) and laboratory parameters of the anticoagulation during the bleeding events will be collected. Furthermore, the intensity of the ECMO treatment (blood flow, sweep gas flow, oxygen requirement) during the bleeding events and the catecholamine use during ECMO implantation will be analyzed. To enhance comparability, intensive care specific treatments (proning, sedation and analgesia, COVID-19 targeted therapy) will be collected and analyzed.

Official Title
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Incidence of Bleeding Complications in Critically Ill COVID-19 Patients With Acute Respiratory Distress Syndrome on Veno-venous ECMO

Conditions
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Acute Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation Complication, Corona Virus Infection

Intervention / Treatment
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* Other: Incidence of bleeding complications in ARDS patients on veno-venous ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill patients with ARDS requiring ECMO support from all three study sites age > 18 years Exclusion Criteria: - Presence of an objective, declared denial to participate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 ARDS patients requiring veno-venous ECMO support<br>Critically ill COVID-19 patients with ARDS requiring ECMO support will be analyzed in this group. Patients from all three study sites will be assessed for participation. | Other: Incidence of bleeding complications in ARDS patients on veno-venous ECMO<br>* All bleeding complications (especially cerebral bleedings) will be analyzed in the study groups. At the bleeding event, laboratory parameters of coagulation will be collected and the intensity of the ECMO treatment<br>|
| Non-COVID-19 ARDS patients requiring veno-venous ECMO support<br>Critically ill Non-COVID-19 patients with ARDS requiring ECMO support will be analyzed in this group. Patients from all three study sites will be assessed for participation. | Other: Incidence of bleeding complications in ARDS patients on veno-venous ECMO<br>* All bleeding complications (especially cerebral bleedings) will be analyzed in the study groups. At the bleeding event, laboratory parameters of coagulation will be collected and the intensity of the ECMO treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral bleedings in critically ill ARDS patients requiring ECMO support | Cerebral bleedings will be analyzed and classified according to cerebral imaging (computed tomography, magnetic resonance tomography) | From date of inclusion of patients into the study, all outcome measures will be analyzed in a time-to-event analysis ranging from ICU admission up to the bleeding event, assessed up to six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-cerebral bleedings in critically ill ARDS patients requiring ECMO support | Bleedings will be classified according to the documentation in the electronic medical reports | From date of inclusion of patients into the study, all outcome measures will be analyzed in a time-to-event analysis ranging from ICU admission up to the bleeding event, assessed up to six months |