ROX Index for Acute Respiratory Failure

(ROX-1 Trial)

Recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the ROX index algorithm can help doctors decide to intubate patients with acute hypoxemic respiratory failure sooner. The ROX index predicts how well a patient might respond to nasal high flow therapy, a type of oxygen treatment. The study compares two groups: one using the ROX index alongside standard care and another using only standard care, to determine if patient outcomes improve. It seeks participants currently experiencing severe breathing problems who need nasal high flow oxygen support and have not been on it for more than an hour. As an unphased trial, this study offers a unique opportunity to contribute to medical knowledge and potentially improve future care for patients with severe breathing issues.

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 prior data suggests that the ROX index algorithm is safe for patients with acute hypoxemic respiratory failure?

Research has shown that the ROX index can predict how well patients might respond to high-flow nasal oxygen therapy, used for breathing problems from severe lung issues. Studies have found that the ROX index effectively identifies patients who may not benefit from this oxygen therapy.

The ROX index is not a medication or treatment that enters the body. Instead, it serves as a tool to help doctors decide when to intubate, which involves placing a tube down the throat to assist with breathing. As a decision-making tool, the ROX index does not have side effects. Its main purpose is to enhance patient care by aiding doctors in making better-informed decisions.

Overall, using the ROX index is considered safe because it guides treatment decisions rather than serving as a treatment itself. Its goal is to help doctors determine the best time for intubation, potentially improving outcomes for patients with severe breathing problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ROX index algorithm because it offers a more personalized approach to managing acute respiratory failure. Unlike the traditional standard of care, which typically relies on fixed criteria for intubation, the ROX index uses real-time data to assess patients' respiratory status and guides adjustments in non-invasive support like high-flow oxygen. This dynamic method could potentially reduce unnecessary intubations, improve patient comfort, and optimize the use of resources in critical care settings.

What evidence suggests that the ROX index algorithm is effective for acute respiratory failure?

Research has shown that the ROX index can effectively predict outcomes in patients with sudden breathing problems treated with a high-flow nasal cannula (HFNC). In this trial, one group of participants will receive the standard of care combined with the ROX index algorithm to guide treatment decisions. For patients with pneumonia, checking the ROX index within 12 hours of starting HFNC can indicate if they can successfully stop using the treatment. Additionally, a specific ROX index level can suggest when HFNC might not be effective, aiding doctors in deciding if intubation is needed. While its accuracy can vary, the ROX index has shown promise in conditions like COVID-19-related breathing issues. Overall, it helps doctors determine the best time to switch to more intensive treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Oriol Roca, MD PhD

Principal Investigator

Universitat Autònoma de Barcelona (UAB)

Are You a Good Fit for This Trial?

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 am not in, nor will I join, another study for the same health issue.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8972647/

The ROX index as a predictor of high-flow nasal cannula ... In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC.

2. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-025-05336-4

Machine learning models compared with current clinical ... The modified ROX index, which requires PaO2, achieved 70% accuracy, 63% sensitivity, 74% specificity, and AUC of 0.65. Conclusions. Decision ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0210569124004297

Predictive performance of ROX index and its variations for ... The performance of ROX index and its variations to predict NIV failure in ICU patients across large public ICU databases was moderate at best.

4. nature.com nature.com/articles/s41598-025-16061-x

Real-time prediction of HFNC treatment failure in acute ... ROX Index: The ROX index threshold of 4.88 was adopted to predict HFNC treatment failure, whereby values below 4.88 were interpreted as likely ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9998832/

Rox Index Dynamics According to High Flow Nasal ... The ROX index can help predict the success of high-flow nasal cannula in coronavirus disease-19-related acute respiratory failure.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10796865/

ROX index performance to predict high-flow nasal oxygen ... ROX index performance to predict high-flow nasal oxygen outcome in Covid-19 related hypoxemic acute respiratory failure. Christophe Girault ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04707729

ROX Index for the Timing of Intubation in Nasal High Flow 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 ...