Effects of Face Mask Continuous Positive Airway Pressure Vs. Noninvasive Ventilation Vs. High-flow Nasal Oxygen on Intubation-free Survival in Acute Hypoxemic Respiratory Failure: the TRIPOD Randomized Clinical Trial

Southeast University, China1,300 enrolled

Overview

Acute hypoxemic respiratory failure (AHRF) is a common indication for admission to an intensive care unit (ICU), with mortality exceeding 50% in cases where invasive mechanical ventilation is needed. Therefore, assessment of the most adequate oxygen strategy to avoid intubation in patients with AHRF deserves consideration.Previous studies have indicated that non-invasive oxygenation strategies, including high-flow nasal oxygen (HFNO), helmet or face mask noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP), are effective in preventing endotracheal intubation in adult patients with AHRF when compared to the standard oxygen therapy. However, the optimal non-invasive oxygenation strategies remain uncertain. This study aim to determine whether CPAP, compared with HFNC or NIV, increase the intubation-free survival during study period in patients with AHRF.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,300

Conditions

Acute Hypoxemic Respiratory Failure High-Flow Nasal Oxygen Therapy Noninvasive Ventilation

Interventions

Continuous Positive Airway PressureDEVICE

1. Patients were placed at a 45-degree supine position, and noninvasive ventilation was delivered to the patient through a face mask connected to an ICU ventilator. 2. PEEP was started at 5 cm H2O with a FiO2 of 0.5 at initiation. PEEP and FiO2 were titrated to maintain SpO2 between 94 and 98%, remaining constant for at least 5 min. 3. CPAP was initiated with a first session of at least 4 h, the minimally required duration of noninvasive ventilation was 16 hours per day for at least 2 calendar days. Between noninvasive-ventilation sessions, patients received HFNO.

High-flow nasal oxygenDEVICE

1. Oxygen was passed through a heated humidifier (MR850, Fisher and Paykel Healthcare) and applied continuously through large-bore binasal prongs, with a gas flow rate of 50 liters per minute and an FiO2 of 0.5 at initiation. HFNO heating temperature was prespecified at 37°C. 2. FiO2 will be titrated to maintain SpO2 between 94 and 98%, remaining constant for at least 5 min. 3. HFNO was applied for at least 2 calendar days.

Non-invasive ventilationDEVICE

1. Patients were placed at a 45-degree supine position, and noninvasive ventilation was also delivered to the patient through a face mask connected to an ICU ventilator. The mask most appropriate for the patient will be selected and adjusted to minimize leakage and pressure points. 2. The inspiratory positive airway pressure (pressure support plus PEEP) was initiated between 12 and 14 cm H2O, PEEP was started at 5 cm H2O with a FiO2 of 0.5 at initiation. FiO2 was titrated to maintain SpO2 between 94 and 98%, remaining constant for at least 5 min. 3. NIV was initiated with a first session of at least 4 h, the minimally required duration of noninvasive ventilation was 16 hours per day for at least 2 calendar days. Between noninvasive-ventilation sessions, patients received HFNO.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age≥18 yrs; 2. A ratio of the partial pressure of arterial oxygen (PaO2) to the FiO2 of 300 mm Hg or less, or a ratio of pulse oximetry oxygen saturation (SpO2) to the FiO2 of 315 or less (SpO2≤97%) and the need for (1) noninvasive positive pressure ventilation with at least 5 cm H2O PEEP, or (2) high-flow nasal cannula at 30L/min or higher, or (3) standard oxygen with oxygen flow rate of at least 10 L/min; 3. Sign informed consent. Exclusion Criteria: 1. Patients that have already received Continuous positive airway pressure, Noninvasive ventilation continuously for more than 24 hours before the screening visit. 2. Previous bout of mechanical ventilation during index hospitalization. 3. Exacerbation of chronic lung disease, including asthma or chronic obstructive pulmonary disease. 4. Moderate to severe cardiac insufficiency (New York Heart Association class \>II or left ventricular ejection fraction\<50%) or cardiogenic pulmonary edema. 5. Hemodynamic dysfunction, defined as vasopressor dose \> 0.3 µg/kg/min of norepinephrine-equivalent to maintain systolic blood pressure \> 90 mm Hg. 6. Impaired consciousness with a Glasgow coma score ≤ 12. 7. Patients with urgent need for intubation, including respiratory or cardiac arrest, respiratory pauses with loss of consciousness or gasping for air, severe hypoxemia defined as SpO2 lower than 90% despite maximal oxygen support. 8. Patients with contraindication to NIV according to the French consensus conference, patient refusal, cardiorespiratory arrest, coma, non-drained pneumothorax, unresolved vomiting, upper airway obstruction, hematemesis or severe facial trauma, thoracic or abdominal surgery in the previous 7 days. 9. A do-not-intubate order at time of inclusion. 10. Pregnancy.

Outcomes

Primary Outcomes

Intubation-free survival rate

The proportion of patients who intubation-free and alive within 28 days after randomization.

Time frame: From randomization to 28 days

Secondary Outcomes

28-day mortality

The proportion of patients who are died within 28 days

Time frame: From randomization to 28 days

Intubation rate within 28 days

The proportion of patients who are intubated within 28 days after randomization

Time frame: From randomization to 28 days

A ranked composite score incorporating death and intubation through day 28

Priority sequence: 28-day mortality, followed by 28-day intubation

Time frame: From randomization to 28 days

Meeting the prespecified criteria for intubation within 28 days.

The proportion of patients who meeting the prespecified criteria for intubation within 28 days.

Time frame: From randomization to 28 days

ICU mortality

The proportion of patients who died within the ICU

Time frame: From randomization to ICU discharge, assessed up to 60 days

In-hospital mortality

The proportion of patients who died within the hospital

Time frame: From randomization to hospital discharge, assessed up to 60 days

Change in Discomfort scale after 1 hour of randomization

The discomfort scale are calculated using 100-mm visual-analogue scale

Time frame: Time from randomization to 1hour

Invasive ventilator-free days at 28 days

Days alive without endotracheal intubation and invasive mechanical ventilation

Time frame: From randomization to 28 days

Circulatory support-free days at day 28

Circulatory support defined as infusion of any vasopressor/inotrope agent for a minimum of 1 hour (i.e. norepinephrine, epinephrine, phenylephrine, vasopressin analogues, angiotensin, dopamine, dobutamine, milrinone or levosimendan)

Time frame: From randomization to 28 days

Time from randomization to an improvement of two points on a seven-category ordinal scale

1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death

Time frame: From randomization to 28 days

ICU-free days at day 28

The number of ICU-free days within 28 days after randomization

Time frame: From randomization to 28 days

Hospital-free days at day 28

The number of Hospital-free days within 28 days after randomization

Time frame: From randomization to 28 days

Effects of Face Mask Continuous Positive Airway Pressure Vs. Noninvasive Ventilation Vs. High-flow Nasal Oxygen on Intubation-free Survival in Acute Hypoxemic Respiratory Failure: the TRIPOD Randomized Clinical Trial

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts