Flow Rates of High-flow Nasal Cannula and Extubation Outcome

Study Overview
=================
Brief Summary
-----------------
This is a single-center, open-label, randomized controlled trial to evaluate the effect of high-flow nasal cannula with a flow rate of 60 L/min versus 40 L/min after planned extubationon on a composite outcome of reintubation and use of NIV.

Detailed Description
-----------------
This is a single-center, open-label, randomized controlled trial to evaluate the effect of high-flow nasal cannula with a flow rate of 60 L/min versus 40 L/min after planned extubationon on a composite outcome of reintubation and use of NIV in patients who are intubated for hypoxemic respiratory failure. [Study Procedures] Set flow rates of HFNC The flow rates of HFNC(high-flow nasal cannula) are set as 40 L/min and 60 L/min, respectively in the two trial groups. Initial FiO2 setting is 100%, which would be titrated down to the minimal level to keep SO2 ≥ 92% within 30 minutes after extubation. After that, the flow rate setting is fixed for 24hrs +/- 6 hrs in the two groups. After that, the flow rate setting in both groups would be tapered to 30 L/min and would be kept for 12 hours. Then, HFNC would be changed to conventional oxygen therapy to keep SpO2≥ 92%. [Outcome Measures] To increase the statistical power of this pilot trial, we used a composite outcome of NIV use and or reintubation in 48 hours for the primary endpoint. Secondary endpoints include mortality of different time points, physiological parameters(respiratory rate, heart rate), ventilation/oxygenation data(PaO2/FiO2 ratio, pH) and patient comfort. Exploratory endpoints include comparison between different flow rate settings. [Primary endpoint] We hypothesized that higher flow setting of HFNC can reduce work of breathing and can increase washout of dead space, which could result in lower re-intubation rate and lower NIV use rate after planned extubation in hypoxemic patients. The primary endpoint is a composite outcome of NIV use or reintubation in 48 hours between two groups of different flow rates. [Secondary endpoints] ICU mortality In-hospital mortality 28-day mortality Time to successful liberation from mechanical ventilation AUC(area under curve) of respiratory rate (0-24 hours) AUC of heart rate (0-24 hours) PaO2/FiO2 ratio at 4 and 24 hours Change of arterial CO2 level(mmHg) at 4 and 24 hours Proportion of respiratory acidosis (arterial blood gas: pH<7.35) at 4 and 24 hours Proportion of Intolerance at 4 and 24 hours Patient comfort (measured by Visual Analog Scale) at 24 hours [Sample size] The event rate of primary endpoint, defined as a composite outcome of NIV use and or reintubation in 48 hours, was assumed to be 40% in the 40 L/min arms and 25% in the 60 L/min. We estimated that with a sample of 165 patients, the study would have 80% power to detect a 15% absolute reduction in proportion of composite outcomes, at a two-sided type I error rate of 5%.

Official Title
-----------------
Effect of Flow Rates of Postextubation High-flow Nasal Cannula on Extubation Outcome: An Open-label, Randomized Controlled Trial

Conditions
-----------------
Hypoxemic Respiratory Failure

Intervention / Treatment
-----------------
* Other: Flow rate setting of high-flow nasal cannula (initially 60L/min)
* Other: Flow rate setting of high-flow nasal cannula (initially 40L/min)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: invasive mechanical ventilation > 48 hours acute hypoxemic respiratory failure(PaO2/FiO2 < 300 mmHg) as a main cause of invasive mechanical ventilation. planned extubation & already passed a spontaneous breathing trial (SBT) Exclusion Criteria: < 20 years of ages refusal to re-intubation with terminal cancer pregnant women with a tracheal stoma or tracheostomy tube in situ not feasible for high-flow nasal cannula(decided by the primary care team) must required to use non-invasive ventilation immediately after extubation (decided by the primary care team)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60 L/min arm<br>The flow rate of HFNC(high-flow nasal cannula) is set as 60 L/min after extubation. | Other: Flow rate setting of high-flow nasal cannula (initially 60L/min)<br>* The flow rates of HFNC(high-flow nasal cannula) is set as 60L/min(temperature:34°C). Initial FiO2 is 100%, which would be titrated down to the minimal level to keep SpO2 ≥ 92% within 30 minutes after extubation. After that, the flow rate setting is fixed for 24hrs +/- 6 hrs; then, is tapered to 30 L/min and kept for 12 more hours. Afterwards, HFNC would be changed to conventional oxygen therapy to keep SpO2≥ 92%.<br>|
| Experimental: 40 L/min arm<br>The flow rate of HFNC(high-flow nasal cannula) is set as 40 L/min after extubation. | Other: Flow rate setting of high-flow nasal cannula (initially 40L/min)<br>* The flow rates of HFNC(high-flow nasal cannula) is set as 40L/min(temperature:34°C). Initial FiO2 is 100%, which would be titrated down to the minimal level to keep SpO2 ≥ 92% within 30 minutes after extubation. After that, the flow rate setting is fixed for 24hrs +/- 6 hrs; then, is tapered to 30 L/min and kept for 12 more hours. Afterwards, HFNC would be changed to conventional oxygen therapy to keep SpO2≥ 92%.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite outcome of NIV(non-invasive ventilation) use or reintubation in 48 hours | Proportion of patients require NIV(non-invasive ventilation) support or reintubation | 48 hours after extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality | Proportion of death in the ICU | ICU stay | 
| In-hospital mortality | Proportion of death in the hospital | Hospital stay | 
| 28-day mortality | Proportion of death in 28 days after extubation | 28 days | 
| Time to successful liberation from mechanical ventilation | Definition of successful liberation from mechanical ventilation: not requiring mechanical ventilation support for > 48 hours | 28 days | 
| AUC(area under curve) of respiratory rate (0-24 hours) | measure respiratory rate every 2 hours during HFNC use | 24 hours | 
| AUC of heart rate (0-24 hours) | measure heart rate every 2 hours during HFNC use | 24 hours | 
| Change of PaO2/FiO2 ratio between 0 and 24th hour | PaO2: from arterial blood gas; FiO2:from HFNC setting | 24 hours | 
| Change of arterial CO2 level(mmHg) between 0 and 24th hour | CO2 level | 24 hours | 
| Proportion of respiratory acidosis (arterial blood gas: pH<7.35) in 24 hours | Respiratory acidosis | 24 hours | 
| Proportion of Intolerance in 24 hours | subjective intolerance (Eg. temperature setting, flow setting, interface....) | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
high-flow nasal cannula, hypoxemic respiratory failure, oxygen therapy, postextubation respiratory failure