Early Versus Delayed Intubation of Patients With COVID-19 (EUDOCO)

• ClinicalTrials.gov Identifier: NCT04632043
• Recruitment Status: Unknown
• First Posted: November 17, 2020
• Last Update Posted: March 3, 2021
• Sponsor: Evangelismos Hospital
• Information provided by (Responsible Party): Ilias Siempos, Evangelismos Hospital

Tracking Information

• First Submitted Date: November 15, 2020
• First Posted Date: November 17, 2020
• Last Update Posted Date: March 3, 2021
• Actual Study Start Date: November 18, 2020
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2020)

Time from onset of severe acute hypoxemic respiratory failure to intubation [ Time Frame: 28 days ]

Difference in time from onset of severe acute hypoxemic respiratory failure to intubation between the two groups will be the primary (feasibility) outcome

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2020)

• Organ failure-free days [ Time Frame: 28 days ]
  Number of days without the need for invasive mechanical ventilation, vasopressors and continuous renal replacement therapy with days after death not to be considered as organ failure-free days
• Need for continuous renal replacement therapy [ Time Frame: 28 days ]
• Ventilator-free days [ Time Frame: 28 days ]
• ICU-free days [ Time Frame: 28 days ]
  Intensive care unit-free days
• Mortality [ Time Frame: 28 days ]
  All-cause ICU-mortality
• Number of severe post-intubation adverse events [ Time Frame: Within 30 minutes from intubation ]
  Cardiac arrest and severe arterial desaturation (defined as SpO2 <80% for >5 minutes)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Versus Delayed Intubation of Patients With COVID-19
• Official Title: Effect of Early versUs Delayed intubatiOn on Clinical Outcomes of Patients With COVID-19 (EUDOCO): a Feasibility Randomized Controlled Trial

Brief Summary

Although management of acute hypoxemic respiratory failure associated with coronavirus disease 2019 (COVID-19) often includes mechanical ventilation, the optimal timing of initiation of invasive mechanical ventilation remains unknown.

We hypothesise that a randomized controlled trial comparing early intubation as opposed to delayed intubation among patients with COVID-19 suffering from severe acute hypoxemic respiratory failure is feasible.

Detailed Description

A common manifestation of COVID-19 is severe acute hypoxemic respiratory failure. Management of acute hypoxemic respiratory failure associated with COVID-19 often includes mechanical ventilation. The optimal timing of initiation of invasive mechanical ventilation remains unknown.

On the one hand, early initiation of invasive mechanical ventilation (i.e. early endotracheal intubation) has been advocated as a means to reduce subsequent possible aerosolization of the virus, as would happen by alternate means of oxygenation/ventilation allowing air leaks. Also, early intubation may prevent the induction of self-inflicted lung injury in patients who breath spontaneously and have high respiratory drive and, therefore, large transpulmonary pressure swings. On the other hand, delaying intubation, by trying alternate means of oxygenation/ventilation, may mean that some of the patients may not be intubated at all and therefore will be protected from the adverse events of invasive mechanical ventilation (such as ventilator-induced lung injury, ventilator-associated pneumonia and ventilator-induced diaphragmatic dysfunction). The latter strategy may also address the unavailability of enough ventilators to meet the increased demand of treating patients with COVID-19.

Given that no randomized controlled trials are currently available to guide clinical practice regarding optimal timing of intubation, we propose a single-center randomized controlled feasibility trial to compare early intubation versus delayed intubation among patients with COVID-19 suffering from severe acute hypoxemic respiratory failure. The aim is that we gain experience and produce pilot data, which could inform the design of a subsequent large multi-center clinical trial.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• COVID-19
• Acute Hypoxemic Respiratory Failure

Intervention

Other: Endotracheal intubation

Endotracheal intubation

Study Arms

• Active Comparator: Early intubation
  Patients with COVID-19 suffering from severe acute hypoxemic respiratory failure (defined as the need for non-rebreather mask or high flow nasal oxygen with setting FiO2 of at least 90% or non-invasive mechanical ventilation to maintain a SpO2 >92%) for at least 48 hours will undergo intubation.
  Intervention: Other: Endotracheal intubation
• Active Comparator: Delayed intubation
  Patients with COVID-19 suffering from severe acute hypoxemic respiratory failure (defined as the need for non-rebreather mask or high flow nasal oxygen with setting FiO2 of at least 90% or non-invasive mechanical ventilation to maintain a SpO2 >92%) for at least 48 hours will continue to receive non-rebreather mask, high-flow nasal oxygen or non-invasive mechanical ventilation in an attempt to avoid intubation.
  Intervention: Other: Endotracheal intubation

Publications *

• Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020 Jun 9;323(22):2329-2330. doi: 10.1001/jama.2020.6825. No abstract available.
• Fan E, Beitler JR, Brochard L, Calfee CS, Ferguson ND, Slutsky AS, Brodie D. COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Lancet Respir Med. 2020 Aug;8(8):816-821. doi: 10.1016/S2213-2600(20)30304-0. Epub 2020 Jul 6.
• Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Satlin MJ, Campion TR Jr, Nahid M, Ringel JB, Hoffman KL, Alshak MN, Li HA, Wehmeyer GT, Rajan M, Reshetnyak E, Hupert N, Horn EM, Martinez FJ, Gulick RM, Safford MM. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020 Jun 11;382(24):2372-2374. doi: 10.1056/NEJMc2010419. Epub 2020 Apr 17. No abstract available.
• Bauer PR, Gajic O, Nanchal R, Kashyap R, Martin-Loeches I, Sakr Y, Jakob SM, Francois B, Wittebole X, Wunderink RG, Vincent JL; ICON Investigators (Supplemental Appendix 1). Association between timing of intubation and outcome in critically ill patients: A secondary analysis of the ICON audit. J Crit Care. 2017 Dec;42:1-5. doi: 10.1016/j.jcrc.2017.06.010. Epub 2017 Jun 16.
• Kang BJ, Koh Y, Lim CM, Huh JW, Baek S, Han M, Seo HS, Suh HJ, Seo GJ, Kim EY, Hong SB. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015 Apr;41(4):623-32. doi: 10.1007/s00134-015-3693-5. Epub 2015 Feb 18.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 15, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2021
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Adult patients with confirmed COVID-19 and severe acute hypoxemic respiratory failure

Exclusion Criteria:

• Postoperative acute respiratory failure (within one week from surgery)
• After cardiac arrest
• Chronic hypoxemic respiratory failure
• Hypercapnic respiratory failure
• No full code
• Lack of equipoise of the clinical team
• Lack of informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Greece

Administrative Information

• NCT Number: NCT04632043
• Other Study ID Numbers: 32635, 13-10-2020
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Within 3 months from publication
• Access Criteria: To anyone who is interested in writing a meta-analysis or review.

• Current Responsible Party: Ilias Siempos, Evangelismos Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Evangelismos Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ilias Siempos, MD, DSc; Evangelismos Hospital

• PRS Account: Evangelismos Hospital
• Verification Date: February 2021