Acute Respiratory Failure (ARF)WHIPNCT07638293
Effect of High Flow Nasal Therapy (HFNC) Weaning Protocols vs Standard of Care on Respiratory Outcomes in Patients With Acute Respiratory Failure
A study testing Protocolized HFNC weaning in people with Acute Respiratory Failure (ARF), run by University of Milan at 2 sites in Italy.
Trial summary
High-flow nasal cannula (HFNC) is a widely used noninvasive respiratory support technique for patients with acute respiratory failure (ARF). It provides heated and humidified oxygen at high flow rates, improving oxygenation, reducing respiratory effort, and enhancing patient comfort. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Failure (ARF)
- What is being tested?
- Protocolized HFNC weaning
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 2 sitesItaly
- Study dates
- 15 May 2026to May 2028
- 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 years
- Presence of acute respiratory failure (ARF)
- Receiving HFNC treatment for ≥24 hours
Who cannot join
- Post-extubation HFNC use or tracheostomized patients
- Respiratory acidosis (pH <7.35) or clinically significant acute hypercapnia (pCO₂ >50 mmHg with worsening from baseline)
- Long-term home NIV or home CPAP use
- Do-not-intubate (DNI) orders precluding escalation to invasive mechanical ventilation
- Life expectancy ≤48-72 hours due to terminal non-respiratory disease
- Neurological impairment or deep sedation preventing safe HFNC use (e.g. coma or severe uncontrolled delirium)
- Technical contraindications to HFNC (i.e. facial trauma, maxillofacial surgery, severe nasal obstruction)
- Refusal to participate or inability to provide informed consent
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Not yet recruiting
Pulmonology Unit, University Hospital "G. Rodolico-San Marco"
Catania, Sicily, 95123
Claudia Crimi, MD PhD, +39 095 3781352, claudia.crimi@unict.it
- Recruiting
Pulmonology Unit, ASST Santi Paolo e Carlo. Department of Health Sciences, University of Milan, Milan (Italy)
Milan, Lombardy, 20142
About this study
Official title: Effect of High Flow Nasal Therapy (HFNC) Weaning Protocols vs Standard of Care on Respiratory Outcomes in Patients With Acute Respiratory Failure: A Randomized Clinical Trial
High-flow nasal cannula (HFNC) is a widely used noninvasive respiratory support technique for patients with acute respiratory failure (ARF). It provides heated and humidified oxygen at high flow rates, improving oxygenation, reducing respiratory effort, and enhancing patient comfort. International guidelines recommend HFNC over conventional oxygen therapy in hypoxemic ARF. However, there is significant variability in clinical practice regarding HFNC discontinuation, and no standardized weaning criteria currently exist. Prolonged HFNC use may increase hospital stay and healthcare costs, while premature discontinuation may lead to respiratory deterioration and the need for further ventilatory support. Previous studies suggest that successful HFNC weaning may be predicted by a Fraction of inspired oxygen (FiO₂) ≤40% and a Respiratory rate-Oxygenation index (ROX index) ≥9.2. The ROX index is calculated as the ratio of peripheral oxygen saturation (SpO₂) divided by fraction of inspired oxygen (FiO₂) to respiratory rate. The primary objective of this study is to compare a standardized HFNC weaning strategy based on ROX index and FiO₂ thresholds with usual clinical practice based on physician judgment. The primary outcome is weaning failure at the first attempt, defined as the need for HFNC reinstitution, noninvasive or invasive mechanical ventilation, or death within 48 hours after discontinuation.
- Conditions
- Acute Respiratory Failure (ARF)
- Being tested
- Protocolized HFNC weaning
- Keywords
- ARF, HFNC, acute respiratory failure, weaning, ROX INDEX
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protocolized HFNC weaningOther
HFNC discontinuation based on ROX index ≥9.2 and FiO₂ ≤40%
| Study group | Role | What they receive |
|---|---|---|
| Non-protocolized weaning | No intervention | Non-protocolized weaning according to standard clinical practice: HFNC assessment every 24 hours and discontinuation based on physician clinical judgment. |
| Protocolized weaning | Experimental | Protocolized weaning using ROX index + FiO₂ Receives: Other: Protocolized HFNC weaning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weaning failure
To compare the percentage of patients who fail HFNC weaning within 48 hours after the first separation attempt using a protocolized HFNC weaning strategy based on ROX index and FiO₂ cut-offs versus standard clinical practice guided by physician judgment.
Measured: Within 48 hours after the first separation attempt
Secondary outcomes (8)
Second-attempt weaning success
To compare the percentage of patients who fail HFNC weaning within 48 hours after the second separation attempt using a protocolized HFNC weaning strategy based on ROX index and FiO₂ cut-offs versus standard clinical practice guided by physician judgment.
Measured: Within 48 hours after the second separation attempt
Length of hospital stay
Comparison of total hospital stay and post-weaning hospital stay between the two study arms.
Measured: From the day of hospital admission until the day of hospital discharge, assessed up to 60 days; and from the day of HFNC discontinuation until the day of hospital discharge, assessed up to 60 days.
In-hospital and 30-day mortality
Comparison of in-hospital mortality and 30-day mortality after discharge between the two study arms.
Measured: From the day of admission to the day of discharge or death (in-hospital mortality) and from the day of admission to 30-day after discharge (30-day mortality)
Predictors of weaning success
Identification of clinical and respiratory variables associated with successful HFNC weaning.
Measured: From enrollment through hospital discharge, an average of 10 days.
Number of days of HFNC treatment from initiation to definitive discontinuation
Number of days of HFNC treatment from initiation to definitive discontinuation
Measured: From the date and time of HFNC initiation until the date and time of definitive HFNC discontinuation, assessed up to 30 days.
Predictors of HFNC treatment duration
Demographic, clinical, radiological and laboratory variables associated with HFNC treatment duration
Measured: From HFNC initiation through hospital discharge, an average of 10 days
Prevalence of diaphragmatic dysfunction assessed by diaphragm thickening fraction (DTF) and diaphragmatic excursion measured by ultrasound between the two study arms.
Comparison of the prevalence of diaphragmatic dysfunction assessed by diaphragmatic ultrasound between patients with successful HFNC weaning and those with weaning failure. Diaphragmatic function will be evaluated using diaphragm thickening fraction (DTF) and diaphragmatic excursion measured by ultrasound.
Measured: 30 minutes before HFNC weaning initiation and 24 hours after weaning completion.
Changes in diaphragmatic function
Evaluation of diaphragmatic ultrasound parameters before and after HFNC discontinuation.
Measured: Before HFNC discontinuation and within 48 hours after weaning attempt
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2026
- Study start15 May 2026 (estimated)
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Failure (ARF)Studies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michele Mondoni, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07638293
- Sponsor's protocol ID
- THE WHIP TRIAL
- Acronym
- WHIP
- Status last verified
- May 2026
- First submitted
- 13 May 2026
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of High Flow Nasal Therapy (HFNC) Weaning Protocols vs Standard of Care on Respiratory Outcomes in Patients With Acute Respiratory Failure: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07638293
- Acronym / sponsor ID
- WHIP / THE WHIP TRIAL
- Conditions
- Acute Respiratory Failure (ARF)
- Keywords
- ARF, HFNC, acute respiratory failure, weaning, ROX INDEX
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 148 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 15 May 2026 (estimated)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 10 Jun 2026 (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.
High-flow nasal cannula (HFNC) is a widely used noninvasive respiratory support technique for patients with acute respiratory failure (ARF). It provides heated and humidified oxygen at high flow rates, improving oxygenation, reducing respiratory effort, and enhancing patient comfort. International guidelines recommend HFNC over conventional oxygen therapy in hypoxemic ARF. However, there is significant variability in clinical practice regarding HFNC discontinuation, and no standardized weaning criteria currently exist. Prolonged HFNC use may increase hospital stay and healthcare costs, while premature discontinuation may lead to respiratory deterioration and the need for further ventilatory support. Previous studies suggest that successful HFNC weaning may be predicted by a Fraction of inspired oxygen (FiO₂) ≤40% and a Respiratory rate-Oxygenation index (ROX index) ≥9.2. The ROX index is calculated as the ratio of peripheral oxygen saturation (SpO₂) divided by fraction of inspired oxygen (FiO₂) to respiratory rate. The primary objective of this study is to compare a standardized HFNC weaning strategy based on ROX index and FiO₂ thresholds with usual clinical practice based on physician judgment. The primary outcome is weaning failure at the first attempt, defined as the need for HFNC reinstitution, noninvasive or invasive mechanical ventilation, or death within 48 hours after discontinuation.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-protocolized weaning | No intervention | –Non-protocolized weaning according to standard clinical practice: HFNC assessment every 24 hours and discontinuation based on physician clinical judgment. |
| Protocolized weaning | Experimental | Other: Protocolized HFNC weaningProtocolized weaning using ROX index + FiO₂ |
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 years
- Presence of acute respiratory failure (ARF)
- Receiving HFNC treatment for ≥24 hours
Key exclusion criteria (8 listed)
- Post-extubation HFNC use or tracheostomized patients
- Respiratory acidosis (pH <7.35) or clinically significant acute hypercapnia (pCO₂ >50 mmHg with worsening from baseline)
- Long-term home NIV or home CPAP use
- Do-not-intubate (DNI) orders precluding escalation to invasive mechanical ventilation
- Life expectancy ≤48-72 hours due to terminal non-respiratory disease
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 |
|---|---|---|
| Protocolized HFNC weaningHFNC discontinuation based on ROX index ≥9.2 and FiO₂ ≤40% | Other | Protocolized weaning |
Primary outcome
Weaning failure
Time frame: Within 48 hours after the first separation attempt
To compare the percentage of patients who fail HFNC weaning within 48 hours after the first separation attempt using a protocolized HFNC weaning strategy based on ROX index and FiO₂ cut-offs versus standard clinical practice guided by physician judgment.
8 secondary outcomes
Second-attempt weaning success
Time frame: Within 48 hours after the second separation attempt
Length of hospital stay
Time frame: From the day of hospital admission until the day of hospital discharge, assessed up to 60 days; and from the day of HFNC discontinuation until the day of hospital discharge, assessed up to 60 days.
In-hospital and 30-day mortality
Time frame: From the day of admission to the day of discharge or death (in-hospital mortality) and from the day of admission to 30-day after discharge (30-day mortality)
Predictors of weaning success
Time frame: From enrollment through hospital discharge, an average of 10 days.
Number of days of HFNC treatment from initiation to definitive discontinuation
Time frame: From the date and time of HFNC initiation until the date and time of definitive HFNC discontinuation, assessed up to 30 days.
Predictors of HFNC treatment duration
Time frame: From HFNC initiation through hospital discharge, an average of 10 days
Prevalence of diaphragmatic dysfunction assessed by diaphragm thickening fraction (DTF) and diaphragmatic excursion measured by ultrasound between the two study arms.
Time frame: 30 minutes before HFNC weaning initiation and 24 hours after weaning completion.
Changes in diaphragmatic function
Time frame: Before HFNC discontinuation and within 48 hours after weaning attempt
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 10 Jun 2026.
- Individual participant dataSharing planned: Undecided
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protocolized HFNC weaning in people with Acute Respiratory Failure (ARF), run by University of Milan at 2 sites in Italy.
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 8 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 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 Michele Mondoni, MD (+39 0240223025, michele.mondoni@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weaning failure (time frame: Within 48 hours after the first separation attempt). 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 10 Jun 2026.