Clinical trial NCT04853953: Cerebral Bleeding in COVID-19 ARDS Patients on Veno-venous ECMO
Official title: Incidence of Bleeding Complications in Critically Ill COVID-19 Patients With Acute Respiratory Distress Syndrome on Veno-venous ECMO
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Respiratory Distress Syndrome
Extracorporeal Membrane Oxygenation Complication
Corona Virus Infection
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Hannover Medical School
name: University Hospital, Bonn
First posted: 2021-04-22
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cerebral bleedings in critically ill ARDS patients requiring ECMO support
timeFrame: 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 outcomes:
measure: Non-cerebral bleedings in critically ill ARDS patients requiring ECMO support
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital Zurich, Institute of Intensive Care
name: Sascha David, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.