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

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

Detailed Description
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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.

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

Conditions
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Chronic Obstructive Pulmonary Disease

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 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

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High oxygen saturation<br>Peripheral oxygen saturation level >94% Intervention: Drug: Oxygen gas | Drug: Oxygen<br>* Administering oxygen to achieve the desired peripheral oxygen saturation<br>|
| Active Comparator: Low oxygen saturation<br>Peripheral oxygen saturation level 88-92% Intervention: Drug: Oxygen gas | Drug: Oxygen<br>* Administering oxygen to achieve the desired peripheral oxygen saturation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxygen, oxidative stress, mortality