Substudy of Protocol 2019-002498-80 - NCT04223050: Comparing Mortality for Low vs High Peripheral Oxygen Saturation in COPD-patients With Acute Exacerbation (O2flow-COPD)

Substudy: Oxygen Therapy in COPD Patients - Oxidative Stress and Mortality

As protocol NCT04223050. This substudy furthermore investigates the role of oxidative stress in the administration of oxygen in COPD patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Oxygen

Detailed Description

Studies have shown that oxidative stress plays a critical role in the pathogenesis of COPD and its comorbidities. Oxidative stress refers to a state in which the activity of oxidants (e.g. reactive oxygen species (ROS)) outweighs that of antioxidants. ROS can be introduced exogenously by for example cigarette smoke and atmospheric pollution, but is also produced endogenously as a byproduct of ATP production in mitochondria or from immune cells during oxidative burst. When high fractions of inspired oxygen are administered, excess O2 can lead to formation of additional ROS, which depletes antioxidants and induces an inflammation with leukocyte-derived inflammatory mediators migrating to the site of injury. In turn, this causes cellular hypertrophy, increased surfactant secretion, and cellular influx of monocytes and mast cells. During the final, fibrotic phase of oxygen toxicity, irreversible, persistent destruction of the pulmonary lining have occurred with collagen disposition, thickening of pulmonary interstitial space, and fibrosis.

This substudy therefore aim to investigate the relation between oxygen therapy in COPD patients admitted with acute exacerbation, oxidative stress, and mortality.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mikkel Brabrand, MD, Ph.D; Phone Number: +4540736373; Email: mikkel.brabrand@rsyd.dk

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Hospital of Southern Denmark, Esbjerg
    • Contact: Mikkel Brabrand; Phone Number: +4540736373; Email: mikkel.brabrand@rsyd.dk
  • Kolding, Denmark, 6000
    • Recruiting
    • Kolding Hospital, Sygehus Lillebælt
    • Contact: Anne Daugaard Thuesen, MD, Ph.D; Email: Anne.Daugaard.Thuesen2@rsyd.dk
    • Principal Investigator: Simon Thorgaard-Rasmussen, MD

Participation Criteria

Eligibility Criteria

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Oxidative stress levels (systemic and lung 8-isopropane levels).	Immediately after study completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation levels (systemic and lung IL-8 levels)		Immediately after study completion
7-day all-cause mortality and 30-day all-cause mortality	extracted from the Danish national registries	30 days
over-all length of hospital stay	calculated from the hospital records	Immediately after study completion
respiratory acidosis	measured as an arterial blood gas analysis with pH < 7.35 and hypercapnia	Immediately after the procedure

Collaborators and Investigators

• Sponsor: Mikkel Brabrand
• Collaborators: Region of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: mortality; oxygen; oxidative stress
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2019-002498-80 substudy

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