Oxygen Targets in Acute Heart Failure With Pulmonary Congestion

Study Overview
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Brief Summary
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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. Liberal oxygenation group = SpO2 target of 96%. 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.

Detailed Description
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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. Liberal oxygenation group = SpO2 target of 96%. 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.

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

Conditions
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Acute Heart Failure, Pulmonary Congestion, Hypoxemia

Intervention / Treatment
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* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Acute (within minutes to days) onset or worsening of subjective dyspnea Oxygen saturation <92% (on arterial blood gas) or need of oxygen 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: More than 4 hours from hospital admission to randomization Suspected infection or sepsis Known severe pulmonary disease Systolic blood pressure <90 mmHg

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 allocation
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liberal oxygenation group<br>SpO2 target of 96% | Drug: Oxygen<br>* 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.<br>|
| Active Comparator: Restrictive oxygenation group<br>SpO2 target of 90%. | Drug: Oxygen<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute heart failure, Pulmonary edema, Oxygen, Pulmonary congestion