Standard vs Targeted Oxygen Therapy Prehospital for Chronic Obstructive Pulmonary Disease (STOP-COPD)

The STOP-COPD trial is a randomized, patient-blinded, prehospital clinical trial designed to evaluate the effect of titrated oxygen therapy compared to standard oxygen treatment in patients with suspected acute exacerbation of chronic obstructive pulmonary disease (AECOPD) treated with inhaled bronchodilators. The primary objective is to determine whether a titrated oxygen strategy targeting SpO₂ 88-92% can reduce 30-day mortality compared to the current standard practice using 100% compressed oxygen as a nebulizer driver.

Study Overview

• Status: Recruiting
• Conditions: COPD Exacerbation; COPD Exacerbation Acute
• Intervention / Treatment: Drug: Titrated Oxygen; Drug: Standard Oxygen

Detailed Description

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. In the prehospital setting, patients with suspected acute exacerbation of COPD (AECOPD) are frequently treated with inhaled bronchodilators driven by 100% oxygen, despite concerns that high-concentration oxygen therapy may worsen hypercapnia and acidosis, leading to increased mortality.

The STOP-COPD trial is a prospective, randomized, parallel-group, superiority trial conducted in the Prehospital Emergency Medical Services, Central Denmark Region. Patients aged 40 years or older with suspected AECOPD requiring inhaled bronchodilators are randomized 1:1 to receive either:

Titrated oxygen therapy: Inhaled bronchodilators driven by compressed air with supplemental oxygen titrated to maintain SpO₂ 88-92%.

Standard treatment: Inhaled bronchodilators driven by 100% compressed oxygen according to standard protocols.

The primary outcome is 30-day all-cause mortality. Secondary outcomes include 24-hour and 7-day mortality, need for invasive or non-invasive ventilation, development of respiratory acidosis upon hospital arrival, ICU admission rate, length of hospital and ICU stay, patient-experienced dyspnoea, and readmission rates. A total of 1,888 patients will be enrolled.

The study is conducted under emergency research regulations allowing enrolment before informed consent, with consent obtained as soon as feasible after hospital admission. This trial seeks to evaluate whether titrating oxygen delivery in the prehospital phase can improve survival and clinical outcomes for patients with AECOPD.

• Study Type: Interventional
• Enrollment (Estimated): 1888
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Martin F Gude, PhD; Phone Number: 0045 25343621; Email: martgude@rm.dk
• Study Contact Backup: Name: Arne Sylvester R Jensen; Phone Number: 22396968; Email: arjens@rm.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Prehospital Emergency Medical Servises, Central Denmark Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over the age of 40
• EMT or Paramedic suspected AECOPD
• Confirmed suspicion of COPD

Exclusion Criteria:

• Bronchospasm due to asthma, allergic reaction or non-COPD conditions
• Known or suspected pregnancy
• Prehospital Non-invasive, invasive or assisted bag mask ventilation
• Allergy to inhaled bronchodilators (Salbutamol)
• Inter-hospital transfer
• More than 2 doses (5 mg salbutamol) inhalation drug, acute treatment by EMS (emergency medical service) personnel, before allocated treatment is initiated
• Suspicion of acute coronary syndrome

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Titrated Oxygen; If the treating EMT or paramedic finds indications for inhaled bronchodilators, this will be done with compressed air 6-8 l/min. as the driver for the nebulizer. The patient will have a Bi-nasal EtCO2 (end-tidal carbon dioxide) meter placed under the nebulizer. This will measure the EtCO2 during the treatment and at the same time oxygen can be titrated through this to a target SpO2 of 88-92%. Repeated treatment will be at the discretion of the treating EMT or paramedic according to SOP (standard operating procedures). Following scenarios regarding SpO2 can occur during treatment: SpO2 <88%: Supplemental oxygen via the EtCO2-meter up to 10 l/min, if higher oxygen levels are needed oxygen will be used as driver for the nebulizer. If the SpO2 remains under 88% additional oxygen can be added via the EtCO2-meter. SpO2 88-92%: No intervention. SpO2 >92%: No intervention. If repeated treatment is not indicated the patient receives oxygen to SpO2 88-92% according SOP.	Drug: Titrated Oxygen; Titrated oxygen strategy - a mix of supplemental oxygen and compressed atmospheric air as driver for inhaled bronchodilators to target SpO2 88-92%; Other Names: Oxygen titration to SpO₂ 88-92% and compressed atmospheric air as nebulizer driver
Active Comparator: Standard Oxygen; If the treating EMT or paramedic finds indication for inhaled bronchodilators, this will be done with oxygen 6-8 l/min. as the driver for the nebulizer. The patient will have a Bi-nasal EtCO2 meter placed under the nebulizer. This will measure the EtCO2 during the treatment and at the same time mask the patient for group allocation. Repeated treatment will be at the discretion of the treating EMT or paramedic according to SOP. Following scenarios regarding SpO2 can occur during treatment: SpO2 <88%: Supplemental oxygen via the EtCO2 -meter up to 10 l/min. SpO2 88-92%: No intervention. SpO2 >92%: No intervention. If repeated treatment is not indicated the patient receives oxygen to SpO2 88-92% according SOP.	Drug: Standard Oxygen; Standard care using compressed oxygen (100%) as driver for inhaled bronchodilators; Other Names: No SpO₂ target restriction and 100% compressed oxygen as nebulizer driver

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality, 30-day	Vital status assessed 30 days after randomization using hospital electronic medical records	Day 30 from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality, 24-hour	Vital status assessed 24 hours after randomization using hospital electronic medical records	24 hours from randomization
Mortality, 7-day	Vital status assessed 7 days after randomization using hospital electronic medical records	Day 7 from randomization
Length of hospital stay	Number of days from hospital admission to hospital discharge, collected from hospital electronic medical records	Day 30 from randomization
ICU admission rate	Proportion of patients admitted to an intensive care unit during the index hospitalization, collected from the electronic hospital medical record	Day 30 from randomization
Length of ICU stay	Number of days spent in the intensive care unit during the index hospitalization, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for NIV (non-invasive ventilation) within 24 hours	Use of non-invasive ventilation recorded within 24 hours of hospital admission, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for NIV within 7 days	Use of non-invasive ventilation recorded within 7 days of hospital admission, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for NIV within 30 days	Use of non-invasive ventilation recorded within 30 days of randomization, collected from the patient's electronic hospital medical record	Day 30 from randomization
Time to NIV	Time from hospital admission to initiation of non-invasive ventilation, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for invasive mechanical ventilation within 24 hours	Initiation of invasive mechanical ventilation within 24 hours of hospital admission, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for invasive mechanical ventilation within 7 days	Initiation of invasive mechanical ventilation within 7 days of hospital admission, collected from the patient's electronic hospital medical record	Day 30 from randomization
In-hospital need for invasive mechanical ventilation within 30 days	Initiation of invasive mechanical ventilation within 30 days of randomization, collected from the patient's electronic hospital medical record	Day 30 from randomization
Time to invasive ventilation	Time from hospital admission to initiation of invasive mechanical ventilation, collected from the patient's electronic hospital medical record	Day 30 from randomization
Proportion of patients with respiratory acidosis on arrival to hospital	Presence of respiratory acidosis (PaCO₂ >6.3 kPa and pH <7.35) assessed via arterial blood gas analysis within 30 minutes after arrival, collected from the patient's electronic hospital medical record	Day 30 from randomization
The degree of acidosis based on the pH (potential of hydrogen) value	Lowest pH value measured from arterial blood gas within 30 minutes of hospital arrival, collected from the patient's electronic hospital medical record	Day 30 from randomization
Patient experienced dyspnoea on a verbal rating scale 0-10	Patient-reported dyspnoea score at hospital arrival on a scale from 0 (no dyspnoea) to 10 (worst imaginable dyspnoea), collected from the prehospital patient record and hospital medical record	Day 30 from randomization
Readmission rate	Proportion of patients readmitted to hospital within 30 days after discharge from index hospitalization, collected from the patient's electronic hospital medical record	Day 30 after discharge
Time to readmission	Number of days from hospital discharge to first hospital readmission within 30 days, collected from the patient's electronic hospital medical record	Day 30 after discharge

Collaborators and Investigators

• Sponsor: Central Denmark Region
• Investigators: Principal Investigator: Martin F Gude, PhD, Central Denmark Region

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 8, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: COPD; Prehospital; COPD Exacerbation; Titrated Oxygen
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 5925 (Other Identifier: COMITATO ETICO TERRITORIALE LOMBARDIA 3); 2022-502003-30-00 (Other Identifier: https://euclinicaltrials.eu)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (IPD) will be made available to researchers whose proposed use of the data has been approved by the local administration. Data will be shared starting 9 months after publication of the primary results and will be accessible until data are no longer stored, according to current ICMJE recommendations and EU data protection regulations.

All trial-related documents (e.g., protocol, statistical analysis plan) will be made publicly available on the trial website. Patient-related data will not be accessible on the website.

• IPD Sharing Time Frame: 9 months after primary results publication; data will remain available until de-identified data are no longer stored according to ICMJE recommendations and EU regulations.
• IPD Sharing Access Criteria: Researchers must submit a methodologically sound proposal for use of the data. Access will be granted following review and approval by the local trial administration. A data-sharing agreement will be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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