ROX Index for Acute Respiratory Failure

(ROX-1 Trial)

Recruiting at 15 trial locations

Overseen By Oriol Roca, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Disqualifiers: Immediate intubation, Pregnancy, Awake ECMO, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

630 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the ROX index algorithm treatment for acute respiratory failure?

The ROX index, which combines breathing rate and oxygen levels, has been shown to help predict outcomes in patients with pneumonia and COVID-19, such as the need for intubation. It has also been used to assess the effectiveness of high flow nasal cannula therapy, suggesting it can be a useful tool in managing acute respiratory conditions. ^{1 2 3 4 5}

How does the ROX index treatment differ from other treatments for acute respiratory failure?

The ROX index is unique because it combines respiratory rate and oxygenation levels to predict the need for more intensive treatments like intubation in patients with acute respiratory failure. Unlike other treatments that directly address symptoms, the ROX index serves as a tool to assess the risk of treatment failure and guide clinical decisions. ^{1 3 4 5 6}

Research Team

Oriol Roca, MD PhD

Principal Investigator

Universitat Autònoma de Barcelona (UAB)

Eligibility Criteria

This trial is for adults over 18 with acute hypoxemic respiratory failure who need nasal high flow (NHF) support. They must have a respiratory rate over 25 breaths/min or oxygen saturation below 92% on standard oxygen therapy. Patients already on NHF can join if it's been less than an hour.

Inclusion Criteria

I used a high-flow nasal cannula for less than an hour before ICU admission.

I needed advanced oxygen because my breathing was very fast or my oxygen levels were too low.

I am over 18 and need high-flow nasal oxygen due to severe breathing problems.

Exclusion Criteria

Patients with no pulmonary infiltrates on chest X-ray

I am under 18 years old.

I need to be put on a breathing machine right away.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Randomization and Initial Treatment

Patients are randomized and begin nasal high flow (NHF) therapy with monitoring of the ROX index and intubation criteria

12 hours

Continuous monitoring in ICU

Ongoing Treatment and Monitoring

Continued NHF therapy with regular assessment of intubation criteria and ROX index adjustments

24-48 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Regular assessments until ICU discharge or death

Treatment Details

Interventions

• ROX index algorithm

Trial Overview The ROX-1 trial tests whether using the ROX index algorithm to decide when to intubate patients with AHRF on NHF leads to better outcomes. It aims to see if this method results in more timely intubations within the first 12 hours of NHF failure compared to usual care.

Participant Groups

Group I: Standard of care + ROX algorithm Experimental Treatment 1 Intervention

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 II: Standard of care Active Control 1 Intervention

Patients will be intubated according to both the standard of care

Who Is Running the Clinical Trial?

Hospital Universitari Vall d'Hebron Research Institute

Lead Sponsor

Trials

253

Recruited

120,000+

Findings from Research

In a study of 2862 patients with sepsis or septic shock, a lower ROX index was associated with higher 28-day mortality, indicating its potential as a prognostic marker.

Patients with a ROX index of 10 or less had a 40% higher risk of death compared to those with a ROX index above 20, highlighting the importance of monitoring this index in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The index of oxygenation to respiratory rate as a prognostic factor for mortality in Sepsis. Lee, CU., Jo, YH., Lee, JH., et al.[2021]

The ROX-HR index, which combines the ROX index with heart rate, shows promise in predicting treatment failure in patients using high flow nasal cannula (HFNC) for acute hypoxemic respiratory failure, with a significant association found at various time points after initiation of therapy.

A ROX-HR index greater than 6.80 at 10 hours is linked to a lower risk of HFNC failure, suggesting that this modified index could be a valuable tool for early intervention in at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate. Goh, KJ., Chai, HZ., Ong, TH., et al.[2022]

The ROX index is a valuable noninvasive tool for predicting the need for intubation in COVID-19 pneumonia patients, with a cut-off point of ≤ 25.26 showing 90.2% sensitivity and 75% specificity based on a study of 69 RT-PCR positive patients.

The study found that all patients with severe COVID-19 required intubation, while only 38% of those with moderate infection did, highlighting the ROX index's strong association with clinical outcomes and its potential to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validity of ROX index in prediction of risk of intubation in patients with COVID-19 pneumonia. Suliman, LA., Abdelgawad, TT., Farrag, NS., et al.[2021]

In a large study of 270,665 patients in Dutch emergency departments, the ROX index was found to be a useful tool for predicting 24-hour mortality in pneumonia patients, showing a slightly higher standardized net benefit than the National Early Warning Score (NEWS) for patients with a predicted mortality of up to 3%.

While the NEWS score had a higher overall accuracy for predicting mortality (area under the curve of 0.92 compared to ROX's 0.87), the ROX index provided more accurate predictions for lower mortality rates, suggesting it could be a valuable first screening tool in emergency settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prediction of 24-h mortality by the respiratory rate and oxygenation index compared with National Early Warning Score in emergency department patients: an observational study. Candel, BGJ., de Groot, B., Nissen, SK., et al.[2023]

The ROX index is a useful early predictor of the risk of intubation in hypoxemic patients using nasal high flow (NHF), with lower values indicating a higher risk.

In a study of 57 patients, those with increased ROX index values at higher flow rates (60 l/min) had worse baseline oxygenation and higher respiratory rates, suggesting that the flow rate during NHF can significantly affect the ROX index and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. Mauri, T., Carlesso, E., Spinelli, E., et al.[2021]

The ROX index, calculated 12 hours after starting high-flow nasal cannula treatment, effectively predicts the need for invasive mechanical ventilation in COVID-19 patients, with a positive predictive value of 59.4% when the threshold is set below 3.85.

In a study of 1,847 hospitalized COVID-19 patients, the ROX index showed high specificity (89.8%) but lower sensitivity (32.3%), indicating it is more reliable for ruling out the need for mechanical ventilation rather than confirming it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of Respiratory Rate-Oxygenation Index in Patients With COVID-19-Related Respiratory Failure. Myers, LC., Mark, D., Ley, B., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

The index of oxygenation to respiratory rate as a prognostic factor for mortality in Sepsis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Validity of ROX index in prediction of risk of intubation in patients with COVID-19 pneumonia. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The prediction of 24-h mortality by the respiratory rate and oxygenation index compared with National Early Warning Score in emergency department patients: an observational study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Validation of Respiratory Rate-Oxygenation Index in Patients With COVID-19-Related Respiratory Failure. [2023]