Comparing Mortality for Low vs High Peripheral Oxygen Saturation in COPD-patients With Acute Exacerbation (O2flow-COPD)

Will Titrated Oxygen Flow to a Peripheral Oxygen Saturation of 88-92% Compared With Oxygen Flow to a Saturation >94% Reduce Mortality in Chronic Obstructive Pulmonary Disease Patients With Acute Exacerbation? - a Randomized Clinical Trial

Chronic obstructive pulmonary disease (COPD) is a common disorder that affects approximately 400,000 Danish citizens. About 3,000-3,500 Danes die yearly because of the disorder, and the costs associated with hospital admissions are estimated to be 535 million Danish kroner (DKK). Patients with COPD risk a worsening of their disorder, and in most cases, this will require hospitalization. One of the used treatments is providing oxygen to the patients via e.g. masks. The recommendations on oxygen treatment are currently based on a study from 2010 where 37% of the participants in this study did not receive the intended treatment, which may have had massive effects on the results. It is worrying that no other studies have shown which oxygen treatment is safest for the patients. As such, we deem it important to study how best to treat the patients.

Our study is of high clinical relevance as hospitals receive patients with worsening of COPD daily. We need more, better data regarding the oxygen treatment of our patients, in order to provide our patients with the best possible care. The purpose of our study is thus to determine which oxygen treatment is best for patients with acute worsening of COPD symptoms. We will use a prospective, randomized controlled open-label trial. We will use two treatments: Treatment 1 is giving oxygen to the patient to reach a peripheral oxygen saturation of above 94%. Treatment 2 is giving oxygen to reach a peripheral oxygen saturation of between 88% and 92%.

Our primary outcome is 30-day all-cause mortality, with secondary outcomes being 7-day all-cause mortality, need for non-invasive ventilation, intubation or intensive care admission, over-all length of hospital stay and respiratory acidosis.

We believe that a lower oxygen saturation percentage may be superior as one study (Austin et al., 2010) showed a lower mortality rate in the group of patients that had a lower peripheral oxygen saturation. Additionally, the risk of respiratory acidosis and hypercapnia were lower. We wish to perform our study in the hospital sector as this study was performed in the prehospital sector and thus their results cannot be translated directly.

Study Overview

• Status: Recruiting
• Conditions: COPD Exacerbation; Chronic Obstructive Pulmonary Disease Exacerbation
• Intervention / Treatment: Drug: Oxygen gas

Detailed Description

Please refer to the full protocol.

• Study Type: Interventional
• Enrollment (Anticipated): 415
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mikkel Brabrand, MD PhD; Phone Number: +45 7918 5934; Email: mikkel.brabrand@rsyd.dk
• Study Contact Backup: Name: Line E. Lilholm Laugesen, MScPH; Phone Number: +45 7918 5934; Email: Line.Emilie.Lilholm.Laugesen@rsyd.dk

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Sydvestjysk Sygehus
    • Contact: Mikkel Brabrand, MD PhD; Phone Number: +45 7918 5934; Email: mikkel.brabrand@rsyd.dk
  • Holbæk, Denmark, 4300
    • Not yet recruiting
    • Holbæk Sygehus
    • Contact: Peter Hallas, MD; Phone Number: 59 48 38 01; Email: phaa@regionsjaelland.dk
  • Kolding, Denmark, 6000
    • Not yet recruiting
    • Sygehus Lillebælt, Kolding
    • Contact: Simon Thorgaard-Rasmussen, MD; Email: Simon.Thorgaard-Rasmussen@rsyd.dk
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Odense University Hospital
    • Contact: Sune Laugesen, MD; Email: Sune.Laugesen@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18 years or older
• ability to give informed consent
• previously diagnosed COPD (either confirmed diagnosis at prior hospital - contact or from their general practitioner or confirmed diagnosis by the treating physician in the emergency department (verified by use of relevant medication))
• admitted with acute exacerbation (acute and worsened shortness of breath) of COPD
• requiring oxygen treatment

Exclusion Criteria:

• Instability at arrival requiring immediate lifesaving treatment, e.g. intubation or non-invasive ventilation, within the first 30 minutes
• Expected total length of stay in hospital < 12 hours
• Planned transfer to another hospital within 12 hours
• Unwilling to have repeated arterial blood gas analyses within the first 12 hours
• Patients judged terminal by treating physician in the emergency department
• Non-residents of the particular country
• Expected impossible follow-up
• Fertile women (<50 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG
• Prior participation in the study

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
Active Comparator: High oxygen saturation; Peripheral oxygen saturation level >94%	Drug: Oxygen gas; Administering oxygen to achieve the desired peripheral oxygen saturation
Active Comparator: Low oxygen saturation; Peripheral oxygen saturation level 88-92%	Drug: Oxygen gas; Administering oxygen to achieve the desired peripheral oxygen saturation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day all-cause mortality	Data is extracted from the Danish national registries.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day all-cause mortality	Data is extracted from the Danish national registries.	7 days
Non-invasive ventilation	The Medical records will be reviewed for documentation on if the patient has been on non-invasive ventilation. This will be reported as proportion of patients on NIV	12 hours
Intubation	The Medical records will be reviewed for documentation on if the patient has been intubated. This will be reported as proportion of patients intubated	12 hours
Intensive care admission	Extracted from the hospital records.	1 day
Overall length of hospital stay	Time calculated from the hospital records	10 days
Respiratory acidosis	Measured as an arterial blood gas analysis with pH > 7.35 and hypercapnia	12 hours

Collaborators and Investigators

• Sponsor: Hospital of South West Jutland
• Collaborators: Odense University Hospital; Holbaek Sygehus; Sygehus Lillebaelt
• Investigators: Principal Investigator: Peter Hallas, MD, Holbaek Sygehus; Principal Investigator: Sune Laugesen, MD, Odense University Hospital; Principal Investigator: Simon Thorgaard-Rasmussen, MD, Sygehus Lillebælt, Kolding

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: COPD; Mortality; Oxygen treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Disease Progression; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2019-002498-80 (EudraCT Number); 19/4298 (Registry Identifier: Region of Southern Denmark)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: (Indsæt senere)

Drug and device information, study documents

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