Nasal High Flow Versus Non-invasive Ventilation for Early Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Hypercapnic Acidosis (HiCOPD)

Nasal High Flow in Early Management of Patients Admitted to the Emergency Department for Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Hypercapnic Acidosis : a Randomized Controlled Non Inferiority Study

The purpose of this study is to determine whether nasal high flow is non inferior to non invasive ventilation (NIV) in the early treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and hypercapnic acidosis in the emergency department (ED). After obtaining informed consent, participants will be randomly assigned to receive either nasal high flow or non invasive ventilation (NIV, reference treatment) as respiratory support. Researchers will compare both respiratory support groups to see if their blood gas analysis and respiration return to normal ranges.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Exacerbation of Chronic Obstructive Pulmonary Disease; Hypercapnic Acidosis; Respiratory Failure With Hypercapnia
• Intervention / Treatment: Device: Ventilatory support via nasal high flow; Device: Ventilatory support via NIV

Detailed Description

Prospective multicenter comparative therapeutic study, with a randomized controlled parallel and open design. Nasal high flow will be compared to NIV (reference treatment) for early treatment of AE-COPD associated with hypercapnic acidosis.

Adult patients admitted to the ED for AE-COPD with hypercapnic acidosis will be randomized to receive either nasal high flow or NIV as ventilatory support. Ventilatory support will be applied in 2h sessions and resumed as needed according to international guidelines for NIV treatment. Close monitoring of clinical and gas parameters will be conducted with repeat assessment and serial blood gas testing at 2h and after each 2h session of respiratory support in the ED (2h, 4h, 6h) and at 24h.

Standard oxygen therapy will be administered as required between ventilatory support sessions to maintain a target peripheral oxygen saturation (SpO2 : 88-92%).

Patient's dyspnea and comfort will be assessed before treatment and at 2h, and after each respiratory support session in the ED Patients will receive standard medical treatment for AE-COPD (bronchodilator, corticosteroids and antibiotics) according to current practice and 2023 global initiative guidelines for the management of COPD (GOLD).

Patients will be followed up at day 28 by means of medical records review and telephone interview

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie LEFEBVRE, PhD; Phone Number: +33 (4) 67 33 85 76; Email: s-lefebvre@chu-montpellier.fr
• Study Contact Backup: Name: Mustapha Sebbane, MD, PhD; Phone Number: +33 (4) 67 33 85 76; Email: m-sebbane@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France
    • Centre Hospitalier Universitaire De Montpellier
  • Nimes, France
    • Centre Hospitalier Universitaire de Nīmes
    • Contact: Pierre-Géraud Claret, MD, PhD
  • Poitiers, France
    • Centre Hospitalier Universitaire De Poitiers
    • Contact: Nicolas Marjanovic, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Adult Patient admitted to the ED for acute exacerbation of COPD (AE-COPD)and respiratory acidosis (PaCO2 > 45 mmHg and pH <7.35), for whom ventilatory assistance by NIV is indicated (SPLF 2017, GOLD2023 recommendations)

Inclusion Criteria:

• Patients with ability to understand and give an informed consent
• Patients affiliated with or who benefit from a social security
• Patients admitted to the emergency department for a clinical suspicion of AE-COPD based on clinical history, physical examination and chest X-ray (SPLF 2017)
• Patients with acute respiratory failure defined by: Respiratory rate ≥ 25 bpm AND/OR Signs of respiratory failure (use of accessory respiratory muscles, paradoxical abdominal movement)
• Patients with respiratory acidosis defined by PaCO2 > 45 mmHg AND pH < 7.35 (measured on arterial blood gas)

Exclusion Criteria:

• Patients who have already received NIV treatment before inclusion (including in-hospital or prehospital, with the exception of NIV at home)
• Contraindication to non-invasive ventilation (SPLF 2017 and GOLD 2023 recommendations)
• Patient uncooperative, agitated, opponent of the technique

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nasal high flow; Nasal high flow will be administered through a heated humidifier (Airvo 3, Fisher and Paykel healthcare) and applied through large bore binasal prongs. Initial gas flow rate will be set at 60 l/min, FiO2 will be adjusted to maintain an SpO2 88-92% and Initial temperature will be set at 37° and reduced according to patient's tolerance. Ventilatory support will be applied in 2h sessions and resumed as needed according to international guidelines for NIV treatment	Device: Ventilatory support via nasal high flow; Ventilatory support will be applied in 2h sessions and resumed as needed according to international guidelines for NIV treatment.
Active Comparator: Non invasive ventilation; NIV will be delivered through a face mask connected to a ventilator with pressure support applied in a noninvasive ventilation mode. The Pressure-support level will be adjusted to obtain an expired tidal volume of 6-8 ml/kg of predicted body weight and a respiratory rate of 25-30 b/min. PEEP (range 5-10 cm of water) and FiO2 will be adjusted to maintain an SpO2 88-92% and to patient's comfort. Ventilatory support will be applied in 2h sessions and resumed as needed according to international guidelines for NIV treatment.	Device: Ventilatory support via NIV; Ventilatory support will be applied in 2h sessions and resumed as needed according to international guidelines for NIV treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PaCO2	PaCO2 will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory assistance and after 2 hours of treatment	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pH	Blood gas parameters will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory support and after 2 hours of treatment	2 hours
Change in PaO2	Blood gas parameters will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory support and after 2 hours of treatment	2 hours
Change in PaCO2	Blood gas parameters will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory support and after sessions of ventilatory support	up to 24 hours
Change in pH	Blood gas parameters will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory support and after sessions of ventilatory support	up to 24 hours
Change in PaO2	Blood gas parameters will be measured from standard laboratory arterial blood gas analysis before the initiation of ventilatory support and after sessions of ventilatory support	up to 24 hours
Respiratory rate	Clinical parameters will be monitored by physician at baseline and throughout ventilatory support sessions, according to the international guidelines for NIV monitoring	up to 24 hours
Treatment failure (composite of change of treatment arm / need for invasive mechanical ventilation/ mortality)	Failure will be defined by a composite of clinical or gasometric worsening or patient intolerance inducing a change of treatment arm/ need for orotracheal intubation and/or mortality (all causes).	Up to Day 28
Weaning from ventilatory support	Delay from initiation of ventilatory support to weaning	Up to Day 28
Signs of increased work of breathing (use of accessory respiratory muscles, paradoxical motion of the abdomen)	Use of accessory respiratory muscles and paradoxical motion of the abdomen will be assessed by physician at baseline and after sessions of ventilatory support, on a 5 point likert scale (from 1 : absence to 5 : maximal use or accessory respiratory muscle and paradoxical motion of the abdomen)	up to 24 hours
Perceived dyspnea	Dyspnea will be assessed by the patient using a Modified Borg scale for dyspnea, at baseline and after sessions of ventilatory support. Difficulty of breathing will be quantified on a scale from 0 : no difficulty at all to 10 : breathing difficulty is maximal.	up to 24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization rate, including hospitalization in critical care units	Proportion of patients requiring hospitalization following ED management	Day 28
Readmission for AE-COPD	Proportion of patients requiring emergency department admission for AE-COPD within 28 days from index admission	Day 28

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Fisher and Paykel Healthcare
• Investigators: Principal Investigator: Mustapha SEBBANE, MD, PhD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: emergency department; non invasive ventilation; respiratory insufficiency; nasal high flow; Hypercapnic Acute Respiratory Failure; chronic obstructive pulmonary disease exacerbation; critical are
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Metabolic Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Acid-Base Imbalance; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Hypercapnia; Acidosis; Acidosis, Respiratory
• Other Study ID Numbers: RECHMPL19_0626; 2022-A02633-40 (Registry Identifier: National Agency for the Safety of Medicines and Health Products)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No