Impact on Mortality of a Strategy Including Continuous Positive Airway Pressure Plus High Flow Nasal Cannula Oxygen Therapy Versus High Flow Nasal Cannula Oxygen Therapy Alone in Patients With de Novo Acute Hypoxemic Respiratory Failure: a Prospective, Randomized Controlled Trial. (HighCPAP)

Impact on Mortality of a Strategy Including Continuous Positive Airway Pressure Plus High Flow Nasal Cannula Oxygen Therapy Versus High Flow Nasal Cannula Oxygen Therapy Alone in Patients With de Novo Acute Hypoxemic Respiratory Failure: a Prospective, Randomized Controlled Trial

De novo hypoxemic acute respiratory failure (hARF) is one of the main causes of intensive care unit (ICU) admission. In de novo hARF, intubation is associated with a dramatic increase in mortality rate. Compared to standard oxygen, the use of high-flow oxygen nasal cannula (HFNC) might be beneficial to prevent intubation and mortality, although the results of trials and meta-analyses are conflicting. Even with HFNC, the intubation rate remains high. This is the reason why adjunctive therapies, administered in addition to HFNC are needed.

Continuous positive airway pressure (CPAP) is one of these adjunctive therapies. CPAP provides high level of positive end-expiratory pressure that ensures lung recruitment, but without adding inspiratory pressure support, which prevents ventilator induced lung injury. In addition, as opposed to pressure support, CPAP is well tolerated during long periods of time. Therefore, applying CPAP in addition to HFNC may reduce intubation rate and in turn mortality rate.

The present trial will evaluate the impact on mortality of a strategy including continuous positive airway pressure plus high flow nasal cannula oxygen therapy versus high flow nasal cannula oxygen therapy alone in patients with de novo acute hypoxemic respiratory failure: a Prospective, Randomized Controlled Trial

Study Overview

• Status: Not yet recruiting
• Conditions: De Novo Hypoxemic Acute Respiratory Failure (hARF)
• Intervention / Treatment: Other: HFNC; Other: CPAP and HFNC

• Study Type: Interventional
• Enrollment (Estimated): 1084
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandre DEMOULE; Phone Number: +33 (0)1 42 16 77 61; Email: alexandre.demoule@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults (≥ 18 years old)
2. Admitted in the ICU for ≤ 24 hours

3. De novo hARF defined by the three following criteria:

   1. Respiratory rate > 25 breaths/min or signs of respiratory distress such as labored breathing or paradoxical inspiration
   2. PaO2/FiO2 ≤ 200 mmHg under HFNC with flow ≥ 45 L/min, actual FiO2 being considered.
   3. Uni or bilateral pulmonary infiltrate on chest X-ray or CT scan
4. Informed consent from the patient or her/his next of kin or another substitute decision maker, or inclusion procedure in emergency if the patient is unable to consent

Exclusion Criteria:

1. Refusal of study participation by the patient or the proxy
2. Anatomical factors precluding the use of a nasal cannula or CPAP
3. Long term oxygen
4. Home CPAP or NIV
5. Hypercapnia indicating NIV (PaCO2 > 45 mmHg)
6. Isolated cardiogenic pulmonary oedema indicating NIV
7. Known pregnancy or breastfeeding
8. Absence of coverage by the French statutory health care insurance system
9. Surgery within the last 6 days
10. Use of vasopressors (norepinephrine>0.3 mcg/kg/min)
11. Glasgow coma scale < 13
12. Urgent need for endotracheal intubation
13. Patients at an end-of-life stage receiving compational oxygenation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HFNC; Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization.	Other: HFNC; Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization; Other Names: High flow nasal cannula oxygen therapy
Experimental: HFNC with CPAP; Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions	Other: HFNC; Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization; Other Names: High flow nasal cannula oxygen therapy; Other: CPAP and HFNC; Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions; Other Names: Continuous positive airway pressure and High flow nasal canulae

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Time to death within the 90 days after randomization	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to intubation.		28 days
Intensity of dyspnea until intubation as assessed by a visual analogic scale from zero (no dyspnea) to 100 (maximum possible dyspnea).		2, 6, 12 and 24 hours
Respiratory rate		6, 12 and 24 hours
ROX index		6, 12 and 24 hours
Evaluation of intolerance to oxygenation technique until intubation	evaluation based on the following physical criteria: eyes dryness, nose dryness and/or feeling of gastric distention	12 and 24 hours
Discomfort associated with the interface as assessed by a visual analogic scale from zero (no discomfort) to 100 (maximum possible discomfort).		12 and 24 hours
Level of oxygenation assessed by blood gas that will be sampled on the request of the physician in charge (clinical purpose only).		First 24 hours or until intubation
Use of NIV for one of the following predefined indication criteria.	the constitution of a clear indication such as acute-on-chronic respiratory failure with respiratory acidosis (pH < 7.35) or acute cardiogenic pulmonary edema,; pre oxygenation before intubation,; fiberoptic bronchoscopy.	through study completion
Death within the ICU		through patient participation period,180 days maximum
Time to death		through patient participation period, an average of 180 days maximum
Death within the hospital and time to death.		through patient participation period,180 days maximum
Number of invasive ventilation-free days at 28 days defined as days alive and without intubation.	One point will be given for each day during the measurement period, i.e. from the first day of randomization to day 28 that patients will be both alive and free of invasive mechanical ventilation. Zero value will be given for patients who die before day 28.	Between day 1 and day 28
Number of HFNC-free days at 28 days defined as days non-intubated, alive and without HFNC.	One point will be given for each day during the measurement period, i.e. from the first day of randomization to day 28 that patients will be both alive and free of HFNO and invasive mechanical ventilation. Zero value will be given for patients who die or are intubated before day 28.	Between day 1 and day 28.
ICU length of stay.		through patient participation period,180 days maximum
Hospital length of stay.		through patient participation period,180 days maximum
Occurrence of any adverse event during the ICU stay, with a particular focus on hospital or ventilator associated pneumonia, non-respiratory infections, cardiac arrhythmia, and cardiac arrest.		through patient participation period,180 days maximum

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Intensive care unit; Non-invasive ventilation; Mortality; Continuous positive airway pressure; Mechanical ventilation; High flow nasal cannula oxygen therapy; De novo hypoxemic acute respiratory failure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: APHP220813

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No