Oxygen Targets in Acute Heart Failure With Pulmonary Congestion (REDOX-AHF)

Restrictive Versus Liberal Oxygenation Targets in Patients With Acute Heart Failure and Pulmonary Congestion - a Randomized Clinical Pilot-trial

This investigator-initiated, prospective, randomized, blinded, multi-center, controlled trial will investigate the effect of a restrictive vs. liberal oxygenation-strategy in patients hospitalized with acute heart failure with pulmonary congestion.

Patients will be randomized 1:1 in the emergency department to either liberal or restrictive oxygenation after providing informed written consent.

1. Liberal oxygenation group = SpO2 target of 96%.
2. Restrictive oxygenation group = SpO2 target of 90%.

The allocation will be concealed through the use of an oxygen-delivery robot, termed O2MATIC. The study will include 122 patients.

Study Overview

• Status: Recruiting
• Conditions: Hypoxemia; Acute Heart Failure; Pulmonary Congestion
• Intervention / Treatment: Drug: Oxygen

Detailed Description

Background:

One million hospitalizations occur each year with a primary diagnosis of acute heart failure in the USA, with comparable numbers in Europe. Most patients with acute heart failure are treated with supplemental oxygen during hospitalization and guidelines recommend initiation of oxygen therapy if SpO2 <90% (class I, level C). However, no clinical trials of oxygen targets in humans with acute heart failure investigating clinically relevant endpoints have been performed.

Primary objective:

To investigate the effect of a restrictive vs. liberal oxygenation-strategy in patients hospitalized with acute heart failure.

Hypothesis:

Restrictive oxygenation is associated with improved clinical outcome compared to liberal oxygenation.

Design: Investigator-initiated, prospective, randomized, blinded, multi-center, controlled trial.

Intervention:

Patients will be randomized 1:1 in the emergency department to either liberal or restrictive oxygenation after providing informed written consent.

1. Liberal oxygenation group = SpO2 target of 96%.
2. Restrictive oxygenation group = SpO2 target of 90%.

Patients will have nasal cannula or oxygen mask placed as the usual care, and oxygen is titrated to the prespecified target range.

Consented patients will be randomly allocated to study groups via the automated web-based system within REDCap. The allocation will be concealed. Time at randomization will be considered as study time zero (T0). All patients will receive usual standard of care except for their oxygen-administration.

The intervention-phase will be 24 h, and hereafter oxygen therapy will be at the discretion of the treating physician.

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Johannes Grand, MD, Phd; Phone Number: +4535453545; Email: johannes.grand@regionh.dk
• Study Contact Backup: Name: Ida Taraldsen, MD

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • Not yet recruiting
    • Bispebjerg Hospital
    • Contact: Olav W Nielsen, MD, DMSc
    • Principal Investigator: Olav W Nielsen, MD DMSc
  • Copenhagen, Denmark, 2650
    • Recruiting
    • Amager-Hvidovre Hospital
    • Contact: Johannes Grand; Email: johannes.grand@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Acute (within minutes to days) onset or worsening of subjective dyspnea
3. Oxygen saturation <92% (on arterial blood gas) or need of oxygen
4. At least one of the following clinical or radiological signs of congestion:

1. Pulmonary rales 2. Chest X-ray or CT with pulmonary congestion 3. Lung ultrasound with multiple B-lines

Exclusion Criteria:

1. More than 4 hours from hospital admission to randomization
2. Suspected infection or sepsis
3. Known severe pulmonary disease
4. Systolic blood pressure <90 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liberal oxygenation group; SpO2 target of 96%	Drug: Oxygen; Patients will have nasal cannula or oxygen mask placed as the usual standard of care. Patients will be screened and randomized in the emergency department to either liberal or restrictive oxygenation after providing informed written consent and oxygen is titrated to the prespecified target range using an automated feedback device (O2MATIC). Consented patients will be randomly allocated to study groups via the web-based system within REDCap. The allocation will be concealed. Time at randomization will be considered as study time zero (T0). All patients will receive usual standard of care except for their O2 management. The intervention will last for 24 h. After 24 h, patients will be switched over to usual care for oxygen therapy. If the treating physician thinks, that the patient need another oxygenation target and it is thought to be harmful to continue with the allocated target, the intervention-phase can be stopped prematurely.
Active Comparator: Restrictive oxygenation group; SpO2 target of 90%.	Drug: Oxygen; Patients will have nasal cannula or oxygen mask placed as the usual standard of care. Patients will be screened and randomized in the emergency department to either liberal or restrictive oxygenation after providing informed written consent and oxygen is titrated to the prespecified target range using an automated feedback device (O2MATIC). Consented patients will be randomly allocated to study groups via the web-based system within REDCap. The allocation will be concealed. Time at randomization will be considered as study time zero (T0). All patients will receive usual standard of care except for their O2 management. The intervention will last for 24 h. After 24 h, patients will be switched over to usual care for oxygen therapy. If the treating physician thinks, that the patient need another oxygenation target and it is thought to be harmful to continue with the allocated target, the intervention-phase can be stopped prematurely.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary parenchymal fluid content after 24 hours	Pulmonary parenchymal fluid content after 24 hours preceded by 10 minutes without oxygen-supplementation assessed noninvasively by the remote dielectric sensing (ReDS) device (Sensible Medical, Netanya, Israel)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Death from all causes	30 days
Days alive out-of-hospital		30 days
Time to freedom from oxygen-supplementation		48 hours
4) Change from baseline in log-transformed biomarkers N-Terminal Pro-Brain Natriuretic Peptide to 24 hours from admission.		24 hours
5) Arterial blood gas concentration after 24 hours preceded by 10 minutes without oxygen-supplementation.		24 hours
Tricuspid annular plane systolic excursion		24 hours
Global longitudinal strain of the right ventricle		24 hours

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital, Hvidovre
• Collaborators: Bispebjerg Hospital
• Investigators: Study Chair: Jens Hove, MD, PhD, Copenhagen University Hospital Amager-Hvidovre Department of Cardiology; Principal Investigator: Johannes Grand, MD, PhD, Copenhagen University Hospital Amager-Hvidovre Department of Cardiology; Study Director: Ida Taraldsen, MD, Copenhagen University Hospital Amager-Hvidovre Department of Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: acute heart failure; Oxygen; Pulmonary edema; Pulmonary congestion
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Signs and Symptoms, Respiratory; Heart Failure; Hypoxia
• Other Study ID Numbers: REDOX

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