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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome; Corona Virus Infection; Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Other: Incidence of bleeding complications in ARDS patients on veno-venous ECMO

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Sascha David, Prof; Phone Number: 0041442552204; Email: Sascha.david@usz.ch

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of critically ill COVID-19 and Non-COVID-19 ARDS patients requiring veno-venous ECMO support.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 ARDS patients requiring veno-venous ECMO support; 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; 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
Non-COVID-19 ARDS patients requiring veno-venous ECMO support; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Hannover Medical School; University Hospital, Bonn
• Investigators: Principal Investigator: Sascha David, Prof, University Hospital Zurich, Institute of Intensive Care

Publications and helpful links

General Publications

• Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5. Epub 2020 Apr 21. No abstract available.
• Makdisi G, Wang IW. Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology. J Thorac Dis. 2015 Jul;7(7):E166-76. doi: 10.3978/j.issn.2072-1439.2015.07.17.
• Rawal G, Yadav S, Kumar R. Acute Respiratory Distress Syndrome: An Update and Review. J Transl Int Med. 2018 Jun 26;6(2):74-77. doi: 10.1515/jtim-2016-0012. eCollection 2018 Jun.
• Seeliger B, Doebler M, Hofmaenner DA, Wendel-Garcia PD, Schuepbach RA, Schmidt JJ, Welte T, Hoeper MM, Gillmann HJ, Kuehn C, Ehrentraut SF, Schewe JC, Putensen C, Stahl K, Bode C, David S. Intracranial Hemorrhages on Extracorporeal Membrane Oxygenation: Differences Between COVID-19 and Other Viral Acute Respiratory Distress Syndrome. Crit Care Med. 2022 Jun 1;50(6):e526-e538. doi: 10.1097/CCM.0000000000005441. Epub 2022 Jan 12.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2021
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 17, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 17, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Coronavirus Infections; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: SD03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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