Target Trial Emulation, Invasive Mechanical VentilationNORMO2NCT06757166
The Effect of NOn-invasive Respiratory Support on outcoMe and Its Risks in SARS-COV-2-related Hypoxemic Respiratory Failure
An observational study of Target Trial Emulation, Invasive Mechanical Ventilation, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
To determine whether early endotracheal intubation compared to late endotracheal intubation affects clinical outcome (duration of invasive mechanical ventilation, mortality). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Target Trial Emulation, Invasive Mechanical Ventilation
- What is being tested?
- endotracheal intubation
- Type of treatment
- Surgery or procedure
- How many people
- 50,000 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2018to Jan 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Patients from the United Stated for which data is registered in the National Covid Cohort Collaborative (N3C).
Who may be able to join
- Hospitalized (inpatient or ICU)
- 18 years or older
- Hypoxemic respiratory failure: S/F<250
- Not yet intubated
Who cannot join
- Do not intubate order
- Presence of tracheostomy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Evert-Jan Wils, PhD, MD contact
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus Medical Centre
Rotterdam, South Holland, 3015GD
Carmen A.T. Reep, MSc, +31628164764, c.reep@erasmusmc.nl
About this study
Official title: Effects of Early vs. Delayed Invasive Mechanical Ventilation: A Target Trial Emulation
To determine whether early endotracheal intubation compared to late endotracheal intubation affects clinical outcome (duration of invasive mechanical ventilation, mortality).
Read the detailed description
Non-invasive respiratory support, especially HFNO is usually well-tolerated, especially in COVID-19 patients and can be applied for a prolonged period of time. However, there is a heated debate whether later/delayed endotracheal intubation (due to HFNO / NIV) increases the risk of lung injury, so-called patient self-inflicted lung-injury (P-SILI). The concept of P-SILI assumes that high forces applied to the lung resulting from strenuous breathing effort generated by the patient exacerbates lung-injury and is associated with adverse clinical outcome. It is therefore important to investigate if a longer period of non-invasive respiratory support before invasive mechanical ventilation is associated with adverse clinical outcome. Thus, it is unknown if delaying invasive ventilation worsens clinical outcome. In this study, the research question is whether early compared to late endotracheal intubation improves clinical outcome (duration of invasive mechanical ventilation, mortality)? The aim is to identify the optimal S/F ratio and respiratory rate thresholds for initiating intubation to either improve survival or reduce the duration of invasive ventilation without compromising survival. This is achieved by comparing 25 dynamic treatment regimes defined by combinations of S/F thresholds (<any, 250, 200, 150, 100) and respiratory rate thresholds (>any, 16, 20, 25, 30). Thresholds indicating less severe illness (e.g., S/F < 250 and RR > 16) are considered 'early intubation,' while thresholds indicating more severe illness (e.g., S/F < 100 and RR > 30) are considered 'late intubation'.
Two sensitivity analyses will be conducted:
- Restricting to patients without hypercapnia (pCO2 < 45), excluding those with missing pCO2 values or pCO2 > 45.
- Including only patients with non-missing Glasgow Coma Scale (GCS) values and adjusting for GCS as a confounder.
Additionally, seven subgroup analyses will be conducted:
- Patients diagnosed with COVID-19
- Patients with a history of COPD
- Patients with a history of CHF
- Patients with BMI ≤ 30
- Patients with BMI > 30
- Patients on high-flow nasal oxygen (HFNO) at time zero
- Patients on non-invasive ventilation (NIV) at time zero
- Being tested
- endotracheal intubation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
endotracheal intubationProcedure or surgery
endotracheal intubation for invasive mechanical ventilation
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day RMTL of mortality
Mortality restricted mean time lost (RMTL) over the 28-day period (area under the cumulative incidence function curve)
Measured: 28 days
28-day mortality risk
Mortality risk at day 28
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2025
- Study start1 Jan 2018
- Primary completionJan 2025 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Target Trial Emulation, Invasive Mechanical VentilationStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 50,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carmen Reep, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06757166
- Sponsor's protocol ID
- 50-56300-98-2113
- Acronym
- NORMO2
- Status last verified
- Jan 2025
- First submitted
- 23 Dec 2024
- Last updated
- 3 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Early vs. Delayed Invasive Mechanical Ventilation: A Target Trial Emulation
- ClinicalTrials.gov ID
- NCT06757166
- Acronym / sponsor ID
- NORMO2 / 50-56300-98-2113
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50,000 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 3 Jan 2025 (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.
To determine whether early endotracheal intubation compared to late endotracheal intubation affects clinical outcome (duration of invasive mechanical ventilation, mortality).
Detailed description
Non-invasive respiratory support, especially HFNO is usually well-tolerated, especially in COVID-19 patients and can be applied for a prolonged period of time. However, there is a heated debate whether later/delayed endotracheal intubation (due to HFNO / NIV) increases the risk of lung injury, so-called patient self-inflicted lung-injury (P-SILI). The concept of P-SILI assumes that high forces applied to the lung resulting from strenuous breathing effort generated by the patient exacerbates lung-injury and is associated with adverse clinical outcome. It is therefore important to investigate if a longer period of non-invasive respiratory support before invasive mechanical ventilation is associated with adverse clinical outcome. Thus, it is unknown if delaying invasive ventilation worsens clinical outcome. In this study, the research question is whether early compared to late endotracheal intubation improves clinical outcome (duration of invasive mechanical ventilation, mortality)? The aim is to identify the optimal S/F ratio and respiratory rate thresholds for initiating intubation to either improve survival or reduce the duration of invasive ventilation without compromising survival. This is achieved by comparing 25 dynamic treatment regimes defined by combinations of S/F thresholds (<any, 250, 200, 150, 100) and respiratory rate thresholds (>any, 16, 20, 25, 30). Thresholds indicating less severe illness (e.g., S/F < 250 and RR > 16) are considered 'early intubation,' while thresholds indicating more severe illness (e.g., S/F < 100 and RR > 30) are considered 'late intubation'.
Two sensitivity analyses will be conducted:
- Restricting to patients without hypercapnia (pCO2 < 45), excluding those with missing pCO2 values or pCO2 > 45.
- Including only patients with non-missing Glasgow Coma Scale (GCS) values and adjusting for GCS as a confounder.
Additionally, seven subgroup analyses will be conducted:
- Patients diagnosed with COVID-19
- Patients with a history of COPD
- Patients with a history of CHF
- Patients with BMI ≤ 30
- Patients with BMI > 30
- Patients on high-flow nasal oxygen (HFNO) at time zero
- Patients on non-invasive ventilation (NIV) at time zero
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients from the United Stated for which data is registered in the National Covid Cohort Collaborative (N3C).
Key inclusion criteria (4 listed)
- Hospitalized (inpatient or ICU)
- 18 years or older
- Hypoxemic respiratory failure: S/F<250
- Not yet intubated
Key exclusion criteria (2 listed)
- Do not intubate order
- Presence of tracheostomy
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 for invasive mechanical ventilation | Procedure or surgery | – |
Primary outcome
28-day RMTL of mortality
Time frame: 28 days
Mortality restricted mean time lost (RMTL) over the 28-day period (area under the cumulative incidence function curve)
28-day mortality risk
Time frame: 28 days
Mortality risk at day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
- Individual participant dataSharing planned: No
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.
Evert-Jan Wils, PhD, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Target Trial Emulation, Invasive Mechanical Ventilation, run by Erasmus Medical Center at 1 site in Netherlands.
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 4 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 3 Jan 2025. 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 Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carmen A.T. Reep, MSc (+31628164764, c.reep@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-day RMTL of mortality (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jan 2025.