COVID-19EUDOCONCT04632043
Early Versus Delayed Intubation of Patients With COVID-19
A study testing Endotracheal intubation in people with COVID-19 and Acute Hypoxemic Respiratory Failure, run by Evangelismos Hospital at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Acute Hypoxemic Respiratory Failure
- What is being tested?
- Endotracheal intubation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteGreece
- Study dates
- 18 Nov 2020to 15 Mar 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients with confirmed COVID-19 and severe acute hypoxemic respiratory failure
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Early versUs Delayed intubatiOn on Clinical Outcomes of Patients With COVID-19 (EUDOCO): a Feasibility Randomized Controlled Trial
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.
Read the 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.
- Conditions
- COVID-19, Acute Hypoxemic Respiratory Failure
- Being tested
- Endotracheal intubation
- Keywords
- COVID-19
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endotracheal intubationOther
Endotracheal intubation
| Study group | Role | What they receive |
|---|---|---|
| Early intubation | Active comparator | 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. Receives: Other: Endotracheal intubation |
| Delayed intubation | Active comparator | 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. Receives: Other: Endotracheal intubation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time from onset of severe acute hypoxemic respiratory failure to intubation
Difference in time from onset of severe acute hypoxemic respiratory failure to intubation between the two groups will be the primary (feasibility) outcome
Measured: 28 days
Secondary outcomes (6)
Organ failure-free 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
Measured: 28 days
Need for continuous renal replacement therapy
Measured: 28 days
Ventilator-free days
Measured: 28 days
ICU-free days
Intensive care unit-free days
Measured: 28 days
Mortality
All-cause ICU-mortality
Measured: 28 days
Number of severe post-intubation adverse events
Cardiac arrest and severe arterial desaturation (defined as SpO2 <80% for >5 minutes)
Measured: Within 30 minutes from intubation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start18 Nov 2020
- Primary completion15 Mar 2021
- Study completion15 Mar 2021
Why it stopped: Insufficient rate of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Evangelismos Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ilias Siempos, Evangelismos Hospital
- Investigators
- Ilias Siempos, MD, DSc, Principal investigator, Evangelismos Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04632043
- Sponsor's protocol ID
- 32635, 13-10-2020
- Acronym
- EUDOCO
- Status last verified
- Feb 2024
- First submitted
- 15 Nov 2020
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
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.
PubMed 32329799Fan 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.
PubMed 32645311Goyal 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.
PubMed 32302078Bauer 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.
PubMed 28641231Kang 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.
PubMed 25691263
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Early versUs Delayed intubatiOn on Clinical Outcomes of Patients With COVID-19 (EUDOCO): a Feasibility Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04632043
- Acronym / sponsor ID
- EUDOCO / 32635, 13-10-2020
- Conditions
- COVID-19, Acute Hypoxemic Respiratory Failure
- Keywords
- COVID-19
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient rate of recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Evangelismos HospitalUniversity, hospital or other
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 15 Mar 2021 (actual)
- First posted
- 17 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early intubation | Active comparator | Other: Endotracheal intubationPatients 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. |
| Delayed intubation | Active comparator | Other: Endotracheal intubationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients with confirmed COVID-19 and severe acute hypoxemic respiratory failure
Key exclusion criteria (7 listed)
- Postoperative acute respiratory failure (within one week from surgery)
- After cardiac arrest
- Chronic hypoxemic respiratory failure
- Hypercapnic respiratory failure
- No full code
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endotracheal intubationEndotracheal intubation | Other | Delayed intubation, Early intubation |
Primary outcome
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
6 secondary outcomes
Organ failure-free days
Time frame: 28 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
Mortality
Time frame: 28 days
Number of severe post-intubation adverse events
Time frame: Within 30 minutes from intubation
Results and safety
The study was stopped early (reason given: Insufficient rate of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Results publication: PubMed 32329799Marini 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.
- Results publication: PubMed 32645311Fan 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.
- Results publication: PubMed 32302078Goyal 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.
- Results publication: PubMed 28641231Bauer 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.
- Results publication: PubMed 25691263Kang 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ilias Siempos, MD, DSc principal investigator
Evangelismos Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Endotracheal intubation in people with COVID-19 and Acute Hypoxemic Respiratory Failure, run by Evangelismos Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Insufficient rate of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time from onset of severe acute hypoxemic respiratory failure to intubation (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04632043, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.