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

NCT ID: NCT06795971

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-23
• Study Completion Date: 2027-12-31

Brief Summary

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.

Conditions

Acute Hypoxemic Respiratory Failure; High-Flow Nasal Oxygen Therapy; Noninvasive Ventilation; Continuous Positive Airway Pressure (CPAP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuous Positive Airway Pressure

Patients will receive continuous positive airway pressure

Group Type: EXPERIMENTAL

Continuous Positive Airway Pressure

Intervention Type: DEVICE

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 oxygen

Patients will receive high-flow nasal oxygen

Group Type: ACTIVE_COMPARATOR

High-flow nasal oxygen

Intervention Type: DEVICE

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 ventilation

Patients will receive non-invasive ventilation

Group Type: ACTIVE_COMPARATOR

Non-invasive ventilation

Intervention Type: DEVICE

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.

Interventions

Continuous Positive Airway Pressure

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.

Intervention Type: DEVICE

High-flow nasal oxygen

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.

Intervention Type: DEVICE

Non-invasive ventilation

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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southeast University, China

OTHER

Sponsor Role: lead

Responsible Party

Ling Liu

Director of Intensive Care Unit, Principal Investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ling Liu, PhD

Role: STUDY_DIRECTOR

Zhongda Hospital, School of Medicine, Southeast University

Locations

Zhongda Hospital, School of Medicine, Southeast University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ling Liu, PhD

Role: CONTACT

liulingdoctor@126.com

+8613851435472

Yi Yang, PhD

Role: CONTACT

yiyiyang2004@163.com

+8613913966300

Facility Contacts

Ling Liu, PhD

Role: primary

liulingdoctor@126.com

+8613851435472

Other Identifiers

TRIPOD Study

Identifier Type: -

Identifier Source: org_study_id