A Trial Comparing High-Flow Nasal Cannula Versus Noninvasive Ventilation on Reintubation and Post-Extubation Respiratory Failure in High-Risk Patients With Systolic Heart Failure (EXTUBATE-HF)

A Prospective Randomized Controlled Trial Comparing High-Flow Nasal Cannula Versus Noninvasive Ventilation on Reintubation and Post-Extubation Respiratory Failure in High-Risk Patients With Systolic Heart Failure

This prospective, open-label randomized controlled pilot trial will enroll participants at the Yale New Haven Hospital. Patients with systolic heart failure, defined as an ejection fraction ≤40%, who require invasive mechanical ventilation (IMV) and are admitted to either the cardiac intensive care unit (CICU) or medical ICU (MICU) will be included.

Subjects meeting eligibility criteria will be randomized 1:1 to one of the two treatment groups:

• Intervention: Extubation to high-flow nasal cannula (HFNC)
• Control: Extubation to non-invasive ventilation (NIV)

Study Overview

• Status: Recruiting
• Conditions: Respiratory Failure; Systolic Heart Failure
• Intervention / Treatment: Device: Airvo 3

Detailed Description

The primary objective is to compare the rates of reintubation and post-extubation respiratory failure for high-risk patients with systolic heart failure extubated to HFNC or NIV. Reintubation will be at the discretion of the attending physician. In doing so, this pilot study will provide the framework for an appropriately powered randomized controlled trial.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elliott Miller, MD, MS; Phone Number: 203-737-6390; Email: elliott.miller@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale New Haven Hospital (CICU or MICU)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient is a male or non-pregnant female greater than or equal to 18 years of age
• The patient is ventilated for greater than 24 hours
• The patient has a systolic left ventricular dysfunction defined as an ejection fraction less than or equal to 40%
• The patient, or legally authorized representative, has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

Exclusion Criteria:

• Patients actively being treated for a COPD exacerbation or known hypercapnia (PaCO2>45) on last Arterial Blood Gas (ABG)
• Patients agitated or uncooperative state
• Patients with do-not-resuscitate orders
• Patients presenting with tracheostomies or anatomical abnormalities interfering with mask fit
• Patients are prisoners
• Patient self-extubates
• Patients with pre-existing NIV prescription (e.g., obstructive sleep apnea, neuromuscular disorders, advanced COPD)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extubation to HFNC; Immediately after planned extubation, the patients assigned to the HFNC group will be continuously treated by HFNC at a flow at the maximally tolerated level for 24 hours.	Device: Airvo 3; Provides effective therapy for acute hypoxemic respiratory failure and post-extubation respiratory support for 24 hours post-extubation.
Active Comparator: Control: Extubation to NIV for 24hrs post-extubation.; The NIV will be immediately initiated after planned extubation using specific, predetermined ventilator settings for 24 hours.	Device: Airvo 3; Provides effective therapy for acute hypoxemic respiratory failure and post-extubation respiratory support for 24 hours post-extubation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of participants with reintubation or respiratory failure within 72 hours post-extubation	Number of participants with reintubation or respiratory failure within 72 hours post-extubation	up to 72 hours post-extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Reintubation or respiratory failure	Number of participants that experience reintubation or respiratory failure (per specific, predetermined criteria) within 48 hours, 7 days, and up to ICU discharge (an average of 30 days)	48 hours, 7 days, and up to ICU discharge (an average of 30 days post-extubation)
Patient intolerance to assigned treatment	Intolerance will be measured as the ability to continue the therapy for the 24 hour treatment period (yes/no).	up to 24 hours post-extubation
Mean length of stay	Mean length of ICU and hospital stay in days	up to 30 days post-extubation
Incidence of ICU mortality	Number of participants with mortality while in ICU	up to ICU discharge (an average of 30 days post-extubation)
Hospital mortality	Number of participants with mortality while in hospital	48 hours, 72 hours, 7 days, and hospital discharge (an average of 30 days post-extubation)
Time to reintubation	Mean number of hours to reintubation after extubation	Immediately post-extubation up to 30 days post-extubation
Respiratory rate-oxygenation (ROX) index and vector	The ROX index, defined as the ratio of oxygen saturation as measured by pulse oximetry (SpO2)/ fraction of inspired oxygen (FIO2) to respiratory rate (RR), is used as a predictor of the need to intubate in patients that received HFNC oxygen therapy. Low ROX index (< 3): Indicates a higher risk of HFNC failure. High ROX index (> 4.88): Suggests a lower risk of HFNC failure.	on day of extubation

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Fisher & Paykel Healthcare Limited
• Investigators: Principal Investigator: Elliott Miller, MD, MS, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Respiratory Tract Diseases; Respiration Disorders; Heart Failure; Respiratory Insufficiency; Heart Failure, Systolic
• Other Study ID Numbers: 2000038572

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: Yes
• product manufactured in and exported from the U.S.: No