Comparing High-flow Nasal Cannula Oxygen and Noninvasive Ventilation to Standard Oxygenation in Non-selected ICU Patients Admitted for Hypoxemic ARF (KISS)

An Adaptive Randomized Controlled Trial (RCT) Comparing High-flow Nasal Cannula Oxygen and Noninvasive Ventilation to Standard Oxygenation in Non-selected Intensive Care Unit Patients Admitted for Hypoxemic Acute Respiratory Failure: The KISS Trial (Key Oxygenation Interventions in Surgical and Non-Surgical Patients)

The goal of this clinical trial is to determine whether one of the two oxygenation or ventilation strategies (NIV and/or HFNO) is superior to standard oxygen to reduce 28-day mortality rate in hypoxemic acute respiratory failure (ARF) patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Procedure: Standard oxygen; Procedure: HFNO; Procedure: NIV

Detailed Description

This randomized controlled trial is a superiority study to test if one of the methods (NIV and/or HFNO) is superior to standard oxygen in ARF patients requiring oxygen. It is an investigator-initiated, multicenter, adaptive, three arms parallel-group trial with a computer-generated allocation sequence and an electronic system-based randomization, with a stratification on medical (then stratification between immunocompromised and non-immunocompromised patients) versus surgical (then stratification between cardiothoracic and abdominal patients).

• Study Type: Interventional
• Enrollment (Estimated): 2100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samir Jaber, MD, PhD; Phone Number: 0033467337271; Email: s-jaber@chu-montpellier.fr
• Study Contact Backup: Name: Audrey DE JONG, MD,PhD; Phone Number: 0033467337271; Email: a-de_jong@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Montpellier University Hospital - Saint Eloi Hospital
    • Contact: Samir Jaber, MD, PhD; Phone Number: 0033467337271; Email: s-jaber@chu-montpellier.fr
    • Principal Investigator: Samir Jaber, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult (age ≥ 18 years)
• A diagnosis of hypoxemic ARF occurring defined as the presence and persistence for more than 30 minutes of hypoxemia (defined by a partial oxygen pressure <60 mm Hg when breathing room air or <80 mmHg when breathing 15 L/min of oxygen or a peripheral oxygen saturation [SpO2] ≤90% when breathing room air and/or a PaO2(partial pressure of oxygen)/FiO2 ratio < 300 mmHg plus either [1] a respiratory rate higher than 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing, such as use of accessory respiratory muscles, paradoxical motion of the abdomen, or intercostal retraction).

Exclusion Criteria:

• Contraindications to NIV and/or HFNO
• Sleep apnea syndrome with home ventilator
• Immediate tracheal intubation
• Requirement for an emergent surgical procedure requiring intubation
• Hypercapnia with a formal indication for NIV (formal indication for NIV with PaCO2 ≥ 50 mmHg or clinical signs of hypercapnia)
• Isolated cardiogenic pulmonary edema (formal indication for NIV). Patients with pulmonary edema associated with another ARF etiology can be included.
• Anatomical factors precluding the use of NIV and/or HFNO
• Patients with limitation or withdrawal of life-sustaining therapies with a do-not-intubate order
• Pregnancy in progress or planned during the study period or breastfeeding women
• Patients protected by law (Art. L1121-6 and L1121-8 of the Code de la Santé Publique): Adult protected by law or patient under guardianship or curatorship
• Subjects not covered by public health insurance
• Absence of written informed consent from the patient or his or her proxy (if present) before inclusion or when possible when the patient has been included in an emergency setting

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard oxygen therapy; Patients will receive standard oxygen. First attempt device in usual care.	Procedure: Standard oxygen; Standard oxygen therapy administered through a Venturi mask allowing a fraction of inspired oxygen (FiO2) setting to maintain a peripheral oxygen saturation (SpO2) ≥ 94%. For medical reasons left to the clinician appreciation (such as a COPD or pulmonary fibrosis or other conditions), a SpO2 ≥ 90% will be accepted.
Experimental: High-Flow nasal cannula therapy (HFNO); Patient will receive HFNO using a humidification system or via the high-flow interface of the ICU ventilator.	Procedure: HFNO; The oxygen therapy will be administered in a semi-sitting position, with a setting of the FiO2 and the oxygen flow rate, to obtain a SpO2 ≥ 94%. For medical reasons left to the clinician appreciation (such as a COPD or pulmonary fibrosis or other conditions), a SpO2 ≥ 90% will be accepted.
Experimental: Noninvasive ventilation therapy (NIV); Between NIV sessions, patients will receive HFNO with the same modalities than the HFNO group.	Procedure: NIV; Systematic application of NIV using two levels of pressure, pressure support (PS) + positive end-expiratory pressure (PEEP) provided using a dedicated NIV ventilator or a standard ICU ventilator with the " NIV module " through a facial mask. The FiO2 will be set to obtain a SpO2 ≥ 94%. For medical reasons left to the clinician appreciation (such as a COPD or pulmonary fibrosis or other conditions), a SpO2 ≥ 90% will be accepted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day-28 mortality	Mortality rates at Day-28	Up to Day-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intubation rate at Day-28	Proportion of patients requiring invasive mechanical ventilation	Day-28
Intubation rate at Day-3	Proportion of patients requiring invasive mechanical ventilation	Day-3
Intubation rate at Day-7	Proportion of patients requiring invasive mechanical ventilation	Day-7
Day-90 mortality	Mortality rates at Day-90	Day-90
Adverse events	Related to the treatment	Up to Day-90
Oxygenation up to Day-7	Proportion of patients with better oxygenation	Up to Day-7
Need of other rescue oxygen therapy up to Day-7	Proportion of patients requiring rescue oxygen therapy	Up to Day-7
ICU length of stay	Duration time in ICU	Up to Day-90
Hospital length of stay	Duration time in Hospital	Up to Day-90
Mortality rates in ICU	Mortality rates in ICU	Up to Day-90
Mortality rates in hospital	Mortality rates in hospital	Up to Day-90

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Study Director: Samir Jaber, MD, PhD, Department of anaesthesia and ICU Saint-Eloi Hospital, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): May 23, 2026
• Study Completion (Estimated): August 23, 2026

Study Registration Dates

• First Submitted: March 31, 2023
• First Submitted That Met QC Criteria: March 31, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Immunocompromised; Non-Invasive Ventilation; Acute Respiratory Failure; Post-Operative; High-Flow Nasal Cannula Oxygen
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome; Respiratory Insufficiency
• Other Study ID Numbers: RECHMPL20_0031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Only the statisticians will have access to the full trial dataset during the enrolment period. All data will be made available to the coordinator at the end of inclusion. Controlled access will be granted to participant-level data sets.

Technical appendix, statistical code, and dataset will be available on demand.

• IPD Sharing Time Frame: Immediately following publication, no end date.
• IPD Sharing Access Criteria: Data will be available for the corresponding author on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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