ROX Index for the Timing of Intubation in Nasal High Flow

Study Overview
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Brief Summary
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Late or delayed intubation in patients with acute hypoxemic respiratory failure (AHRF) treated with nasal high flow (NHF) is associated with increased patient mortality. The ROX index has been designed and validated to predict outcome of NFH therapy by identifying those patients with a high risk of NHF failure and those with a high probability of success. Whether or not the ROX index may improve patient outcome remains to be shown. To do so, a strategy using the ROX index must lead to earlier intubation than commonly-used criteria. The objective of the ROX-1 trial is to assess whether the use of an algorithm incorporating the ROX index to standard of care for the time to intubation in patients with AHRF supported with NHF isassociated with an increase in the proportion of patients who are intubated within the first 12 hours among those patients who fail on NHF.

Official Title
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ROX Index Compared to Standard of Care for the Timing of Intubation in Patients Supported by Nasal High Flow: a Randomized Controlled Trial

Conditions
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Acute Hypoxemic Respiratory Failure

Intervention / Treatment
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* Diagnostic Test: ROX index algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consecutive patients older than 18 years with acute hypoxemic respiratory failure who need to be supported with nasal high flow (NHF) will be considered for inclusion. Criteria for initiation of NHF if they had a respiratory rate > 25 breaths/min and/or pulse oximetry (SpO2) < 92% while receiving standard oxygen administered through a facemask at 10 L/mn or more. Patients already treated with NHF for acute respiratory failure prior to ICU admission will be enrolled if duration of NHF prior to randomization does not exceed one hour. Exclusion Criteria: Patients younger than 18 years old. Patients with indication for immediate intubation. Patients treated with NHF for more than 1h prior to randomization. Patients with do-not-intubate order. Patients electively intubated for diagnostic or therapeutic procedures. (fibrobronchoscopy, surgery). Patients with no pulmonary infiltrates on chest X-ray Patient with post-extubation AHRF. Awake ECMO. Pregnancy. Refusal to participate or participation in another interventional study with the same primary outcome.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The ROX-1 trial is an international, multicenter, parallel, open-label randomized controlled two-arm trial that will be performed in patients with AHRF, supported by nasal high flow, who are admitted to the intensive care unit (ICU). Patients will be randomized after stratification according to PaO2/FiO2, through an online automatic centralized and computerized system to one of the study groups (1:1 ratio): traditional intubation criteria or traditional intubation criteria + ROX criteria.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care<br>Patients will be intubated according to both the standard of care | |
| Experimental: Standard of care + ROX algorithm<br>In the intervention arm, patients will be intubated according to both the standard of care and the ROX index, whichever are met first. If the patient has a ROX index below different thresholds after different time-point within the first 12 hours since randomization, the NHF support will be increased to the maximum tolerated flow (up to 60L/min) and FIO2 of 1 and subsequently titrated with the target SpO2. Then, the ROX index will be recalculated in 30 minutes. If the patient is already treated with to 60L/min) and FIO2 of 1 and no further increase could be done, the ROX index will be recalculated after 30 minutes of full NHF support. Then: 1) if the ΔROX is <0 the patient will be intubated; 2) if the ΔROX is 0-0.5, the ΔROX will be reassessed in 30 minutes; and 3) if the ΔROX is >0.5 the patient will not be intubated, NHF will be managed as protocolized and respiratory condition will be reassessed every two hours or at any new clinical deterioration. | Diagnostic Test: ROX index algorithm<br>* The thresholds of the ROX index for intubation are the following: After 2 hours of HFNC: ROX <2.85. After 4 and 6 hours of HFNC: ROX <3.47 After 8, 10 and 12 hours of HFNC: ROX <3.85 If the ROX index is between the abovementioned thresholds and 4.88, the NHF support will be also increased to the maximum tolerated flow (up to 60L/min) and FIO2 of 1 and subsequently titrated with the target SpO2. If the patient is already treated with to 60L/min) and FIO2 of 1 and no further increase could be done and the ROX index will be recalculated after 30 minutes of full NHF support. The ROX index will be recalculated in 30 minutes: 1) if the ΔROX is <0 the patient will be intubated; 2) if the ΔROX is 0-0.5, the ΔROX will be reassessed in 20 minutes; and 3) if the ΔROX is >0.5 the patient will not be intubated, NHF will be managed as protocolized and respiratory condition will be reassessed every two hours or at any new clinical deterioration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early intubation | Proportion of patients who will be intubated in the first 12 hours after inclusion between the two groups | 12 hours since HFNC onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intubation rate | Rate of total intubations (early plus late) | Through ICU length of stay, an average of 30 days | 
| 28-day mortality | Mortality within the first 28 days since randomization | 28 days | 
| ICU mortality | Mortality in the ICU | Through ICU length of stay, an average of 30 days | 
| Hospital mortality | Mortality in the hospital | Through hospital length of stay, an average of 45 days | 
| Ventilator-free days within the first 28 days | Days free of mechanical ventilation in the first 28 days in those patients who needed to be intubated | 28 days since the intubation | 
| Use of rescue treatments | Need for rescue therapies for refractory hypoxemia | Through ICU length of stay, an average of 30 days | 
| Need for tracheotomy | Need for tracheotomy | Through ICU length of stay, an average of 30 days | 
| ICU length of stay | Days admitted in the ICU | Through ICU length of stay, an average of 30 days | 
| Hospital length of stay | Days admitted in the hospital | Through hospital length of stay, an average of 45 days | 
| Rate of complications during tracheal intubation | Proportion of complications that appear during endotracheal intubation in those patients who fail | Through ICU length of stay, an average of 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High flow nasal cannula, Nasal high flow, High flow oxygen therapy