Effect of High Flow Nasal Therapy (HFNC) Weaning Protocols vs Standard of Care on Respiratory Outcomes in Patients With Acute Respiratory Failure

NCT07638293 | Recruiting

• 1 other identifier: THE WHIP TRIAL
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 2

Brief 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. 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)

Keywords

ARF; HFNC; acute respiratory failure; weaning; ROX INDEX

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 48 hours after the first separation attempt

Secondary Outcomes (8)

• Second-attempt weaning success

  Within 48 hours after the second separation attempt

• Length of hospital stay

  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

  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

  From enrollment through hospital discharge, an average of 10 days.

• Number of days of HFNC treatment from initiation to definitive discontinuation

  From the date and time of HFNC initiation until the date and time of definitive HFNC discontinuation, assessed up to 30 days.

Study Arms (2)

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

Other: Protocolized HFNC weaning

Interventions

Protocolized HFNC weaning OTHER

HFNC discontinuation based on ROX index ≥9.2 and FiO₂ ≤40%

Protocolized weaning

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Presence of acute respiratory failure (ARF)
• Receiving HFNC treatment for ≥24 hours

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Milan: lead

Study Sites (2)

Pulmonology Unit, ASST Santi Paolo e Carlo. Department of Health Sciences, University of Milan, Milan (Italy)

Milan, Lombardy, 20142, Italy

RECRUITING

Pulmonology Unit, University Hospital "G. Rodolico-San Marco"

Catania, Sicily, 95123, Italy

NOT YET RECRUITING

Central Study Contacts

Michele Mondoni, MD

CONTACT

+39 0240223025; michele.mondoni@unimi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associated Professor of Respiratory Medicine

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: June 10, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 10, 2026

Record last verified: 2026-05

Locations

IT (2)