ROX Index for the Timing of Intubation in Nasal High Flow

NCT ID: NCT04707729

Last Updated: 2024-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

630 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-09

Study Completion Date

2025-06-30

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.

Detailed Description

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This is a pilot study to assess whether the use of an algorithm incorporating the ROX index to traditional criteria for intubation in patients with AHRF supported with NHF is:(i) feasible; (ii) associated with a decreased time to intubation.

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). Ethics approval will be sought from each participating institution before starting enrolmentand consent will be obtained for each patient. The coordinating center will be Hospital Universitari Vall d'Hebron in Barcelona, Spain.

All consecutive patients older than 18 years with acute hypoxemic respiratory failure who need to be supported with nasal high flow (NHF) will be enrolled if they meet all the following criteria:

1. Respiratory rate \> 25 breaths/min
2. A pulse oximetry (SpO2)\<92% while receiving standard oxygen administered through a facemask at 10L/min or more.
3. Pulmonary infiltrate on chest X-ray.

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.

Non-inclusion criteria are: Patients younger than 18 years old, Patients with indication for immediate intubation, patients with do not intubate order, patients electively intubated for diagnostic or therapeutic procedure (fibrobronchoscopy, surgery), patient with post-extubation AHRF, awake ECMO, pregnancy and refusal to participate or participation in another interventional study with the same primary outcome. Reasons for non-inclusion in screend patients will be registered.

Patients admitted to the ICU with acute hypoxemic respiratory failure will be screened, included after having received study information, and signed informed consent. They will be randomized after stratification according to PaO2/FiO2, through an online 4 automatic centralized and computerized system to one of the study groups (1:1 ratio): traditional intubation criteria or traditional intubation criteria + ROX criteria. Due to the nature of the intervention, blinding will not be feasible.

Randomization will be stratified to PaO2/FiO2 in order to analyse separately those patients with a PaO2/FiO2 ratio ≤ 200 and \> 200. Intubation criteria for each study arm HFNC failure will be defined as the subsequent need for invasive MV. After randomization, clinicians will set NHF to the maximum tolerated flow (up to 60L/min) and FIO2 will be titrated targeting a SpO2 between 94-98% (88-92% in case of underlying chronic lung disease). In both groups, the presence of intubation criteria will be assessed every two hours during the first 12 hours after randomization and after any clinical deterioration. Between 12 and 24 hours of NHF therapy, the presence of intubation criteria will be assessed every 4 hours. Beyond the first 24 hours after randomization, the presence of intubation criteria will be assessed once a day and after any clinical deterioration.

In the intervention arm, patients will be intubated according to both the traditional intubation criteria and the ROX index, which ever are met first. Moreover, during the first two hours of NHF supportive therapy after randomization, the ROX index will be measured every 30 minutes. If the patient has a ROX index \<2.85, 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 assessed 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.

Between the 2 and 6 hours after randomization, the ROX index will be measured every 60 minutes. If the ROX index is \<3.47, 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. As described before, 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 hourly or at any new clinical deterioration.

Finally, between the 6 and 12 hours after randomization, the ROX index will be measured every 60 minutes. If the ROX index is \<3.85, 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. 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. Then, the ROX index will be calculated in 30 minutes and decision of intubation will be taken according to the previously described ΔROX. In the ROX group, if there is any clinical deterioration beyond the first 12 hours of treatment , the algorithm should be restarted from the beginning, considering time 0 as the time when new clinical deterioration started. End of follow-up. Enrolled patients will be followed for one month or until ICU discharge or death, whichever occurs first.

Conditions

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Acute Hypoxemic Respiratory Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Standard of care

Patients will be intubated according to both the standard of care

Group Type NO_INTERVENTION

No interventions assigned to this group

Standard of care + ROX algorithm

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.

Group Type EXPERIMENTAL

ROX index algorithm

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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ROX index algorithm

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.

Intervention Type DIAGNOSTIC_TEST

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Oriol Roca, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universitat Autònoma de Barcelona (UAB)

Locations

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Rush University Chicago Hospital

Chicago, Illinois, United States

Site Status RECRUITING

First Affiliated Hospital of Chongqing Medical University

Chongqing, , China

Site Status NOT_YET_RECRUITING

The Second Military Medical University Hospital

Shanghai, , China

Site Status RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, , China

Site Status NOT_YET_RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital de Ciudad Real

Ciudad Real, , Spain

Site Status RECRUITING

Hospital Civil Fray Antonio Alcalde

Guadalajara, , Spain

Site Status RECRUITING

Hospital Son Llàtzer

Palma de Mallorca, , Spain

Site Status RECRUITING

Hospital Parc Taulí

Sabadell, , Spain

Site Status RECRUITING

Hospital Moisès Broggi

Sant Joan Despí, , Spain

Site Status RECRUITING

Hospital Virgen de la Salud

Toledo, , Spain

Site Status RECRUITING

Countries

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United States China Spain

Central Contacts

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Oriol Roca, MD PhD

Role: CONTACT

+34932746209

Facility Contacts

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Jie Li, MD PhD

Role: primary

Jun Duan

Role: primary

Wei Zhang, MD PhD

Role: primary

Ming Zhong, MD

Role: primary

Andrés Pacheco Reyes, MD

Role: primary

Role: backup

Irene Dot, MD

Role: primary

Ramón Ortiz

Role: primary

Miguel Ibarra, MD

Role: primary

Gemma Rialp, MD PhD

Role: primary

Oriol Roca, MD PhD

Role: primary

Melinda Popoviciu, MD

Role: primary

Gonzalo Hernández, MD PhD

Role: primary

References

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Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995 Sep 28;333(13):817-22. doi: 10.1056/NEJM199509283331301.

Reference Type BACKGROUND
PMID: 7651472 (View on PubMed)

Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernandez G, Garcia-de-Acilu M, Frat JP, Masclans JR, Ricard JD. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1368-1376. doi: 10.1164/rccm.201803-0589OC.

Reference Type BACKGROUND
PMID: 30576221 (View on PubMed)

Roca O, Messika J, Caralt B, Garcia-de-Acilu M, Sztrymf B, Ricard JD, Masclans JR. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016 Oct;35:200-5. doi: 10.1016/j.jcrc.2016.05.022. Epub 2016 May 31.

Reference Type BACKGROUND
PMID: 27481760 (View on PubMed)

Other Identifiers

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PR(AG)454/2020

Identifier Type: -

Identifier Source: org_study_id

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