Acute Hypoxemic Respiratory FailureTRIPODNCT06795971
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
A study testing Continuous Positive Airway Pressure, High-flow nasal oxygen and Non-invasive ventilation in people with Acute Hypoxemic Respiratory Failure and High-Flow Nasal Oxygen Therapy, run by Southeast University, China at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, High-Flow Nasal Oxygen Therapy, Noninvasive Ventilation
- What is being tested?
- Continuous Positive Airway Pressure, High-flow nasal oxygen and Non-invasive ventilation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,300 participants
- Where
- 1 siteChina
- Study dates
- 23 Jan 2025to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥18 yrs;
- 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;
- Sign informed consent.
Who cannot join
- Patients that have already received Continuous positive airway pressure, Noninvasive ventilation continuously for more than 24 hours before the screening visit.
- Previous bout of mechanical ventilation during index hospitalization.
- Exacerbation of chronic lung disease, including asthma or chronic obstructive pulmonary disease.
- Moderate to severe cardiac insufficiency (New York Heart Association class >II or left ventricular ejection fraction<50%) or cardiogenic pulmonary edema.
- Hemodynamic dysfunction, defined as vasopressor dose > 0.3 µg/kg/min of norepinephrine-equivalent to maintain systolic blood pressure > 90 mm Hg.
- Impaired consciousness with a Glasgow coma score ≤ 12.
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- 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.
- 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.
- A do-not-intubate order at time of inclusion.
- Pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Zhongda Hospital, School of Medicine, Southeast University
Nanjing, Jiangsu, 210009
Ling Liu, PhD, +8613851435472, liulingdoctor@126.com
About this study
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)
- Being tested
- Continuous Positive Airway Pressure, High-flow nasal oxygen, Non-invasive ventilation
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Positive Airway PressureDevice
- 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.
- 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.
- 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
- 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.
- FiO2 will be titrated to maintain SpO2 between 94 and 98%, remaining constant for at least 5 min.
- HFNO was applied for at least 2 calendar days.
Non-invasive ventilationDevice
- 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.
- 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.
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Continuous Positive Airway Pressure | Experimental | Patients will receive continuous positive airway pressure Receives: Device: Continuous Positive Airway Pressure |
| High-flow nasal oxygen | Active comparator | Patients will receive high-flow nasal oxygen Receives: Device: High-flow nasal oxygen |
| Non-invasive ventilation | Active comparator | Patients will receive non-invasive ventilation Receives: Device: Non-invasive ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intubation-free survival rate
The proportion of patients who intubation-free and alive within 28 days after randomization.
Measured: From randomization to 28 days
Secondary outcomes (12)
28-day mortality
The proportion of patients who are died within 28 days
Measured: From randomization to 28 days
Intubation rate within 28 days
The proportion of patients who are intubated within 28 days after randomization
Measured: 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
Measured: 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.
Measured: From randomization to 28 days
ICU mortality
The proportion of patients who died within the ICU
Measured: From randomization to ICU discharge, assessed up to 60 days
In-hospital mortality
The proportion of patients who died within the hospital
Measured: 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
Measured: Time from randomization to 1hour
Invasive ventilator-free days at 28 days
Days alive without endotracheal intubation and invasive mechanical ventilation
Measured: 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)
Measured: 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
Measured: From randomization to 28 days
ICU-free days at day 28
The number of ICU-free days within 28 days after randomization
Measured: From randomization to 28 days
Hospital-free days at day 28
The number of Hospital-free days within 28 days after randomization
Measured: From randomization to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2025
- Study start23 Jan 2025
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southeast University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ling Liu, Southeast University, China
- Investigators
- Ling Liu, PhD, Study director, Zhongda Hospital, School of Medicine, Southeast University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06795971
- Sponsor's protocol ID
- TRIPOD Study
- Acronym
- TRIPOD
- Status last verified
- Feb 2025
- First submitted
- 11 Jan 2025
- Last updated
- 26 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06795971
- Acronym / sponsor ID
- TRIPOD / TRIPOD Study
- Conditions
- Acute Hypoxemic Respiratory Failure, High-Flow Nasal Oxygen Therapy, Noninvasive Ventilation, Continuous Positive Airway Pressure (CPAP)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,300 participants (estimated)
- Lead sponsor
- Southeast University, ChinaUniversity, hospital or other
- Study start
- 23 Jan 2025 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Continuous Positive Airway Pressure | Experimental | Device: Continuous Positive Airway PressurePatients will receive continuous positive airway pressure |
| High-flow nasal oxygen | Active comparator | Device: High-flow nasal oxygenPatients will receive high-flow nasal oxygen |
| Non-invasive ventilation | Active comparator | Device: Non-invasive ventilationPatients will receive non-invasive ventilation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age≥18 yrs;
- 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;
- Sign informed consent.
Key exclusion criteria (10 listed)
- Patients that have already received Continuous positive airway pressure, Noninvasive ventilation continuously for more than 24 hours before the screening visit.
- Previous bout of mechanical ventilation during index hospitalization.
- Exacerbation of chronic lung disease, including asthma or chronic obstructive pulmonary disease.
- Moderate to severe cardiac insufficiency (New York Heart Association class >II or left ventricular ejection fraction<50%) or cardiogenic pulmonary edema.
- Hemodynamic dysfunction, defined as vasopressor dose > 0.3 µg/kg/min of norepinephrine-equivalent to maintain systolic blood pressure > 90 mm Hg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous Positive Airway Pressure1. 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. | Device | Continuous Positive Airway Pressure |
| High-flow nasal oxygen1. 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. | Device | High-flow nasal oxygen |
| Non-invasive ventilation1. 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. | Device | Non-invasive ventilation |
Primary outcome
Intubation-free survival rate
Time frame: From randomization to 28 days
The proportion of patients who intubation-free and alive within 28 days after randomization.
12 secondary outcomes
28-day mortality
Time frame: From randomization to 28 days
Intubation rate within 28 days
Time frame: From randomization to 28 days
A ranked composite score incorporating death and intubation through day 28
Time frame: From randomization to 28 days
Meeting the prespecified criteria for intubation within 28 days.
Time frame: From randomization to 28 days
ICU mortality
Time frame: From randomization to ICU discharge, assessed up to 60 days
In-hospital mortality
Time frame: From randomization to hospital discharge, assessed up to 60 days
Change in Discomfort scale after 1 hour of randomization
Time frame: Time from randomization to 1hour
Invasive ventilator-free days at 28 days
Time frame: From randomization to 28 days
Circulatory support-free days at day 28
Time frame: From randomization to 28 days
Time from randomization to an improvement of two points on a seven-category ordinal scale
Time frame: From randomization to 28 days
ICU-free days at day 28
Time frame: From randomization to 28 days
Hospital-free days at day 28
Time frame: From randomization to 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ling Liu, PhD study director
Zhongda Hospital, School of Medicine, Southeast University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Continuous Positive Airway Pressure, High-flow nasal oxygen and Non-invasive ventilation in people with Acute Hypoxemic Respiratory Failure and High-Flow Nasal Oxygen Therapy, run by Southeast University, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ling Liu, PhD (+8613851435472, liulingdoctor@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intubation-free survival rate (time frame: From randomization to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2025.