Prehospital Targeted Oxygen versus Standard Oxygen Therapy in Acute Exacerbation of COPD: Randomized Controlled Trial

The primary objective of the study is to determine whether prehospital **titrated oxygen** in patients with suspected Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) will decrease 30-day mortality compared to patients receiving standard care. This is clinically relevant as reducing mortality in AECOPD patients can significantly improve patient outcomes and reduce healthcare burdens.

Secondary objectives include:

• To determine whether a prehospital titrated oxygen strategy for AECOPD patients will have a positive effect on experienced dyspnoea, rated on a scale from 0-10, compared to patients receiving standard care.
• To determine whether a prehospital titrated oxygen strategy for AECOPD patients will reduce the in-hospital need for non-invasive ventilation (NIV) or invasive ventilation compared to patients receiving standard care.
• To determine whether a prehospital titrated oxygen strategy for AECOPD patients will result in a reduced 24-hour and 7-day mortality compared to patients receiving standard care.
• To determine whether a prehospital titrated oxygen strategy for AECOPD patients will reduce the proportion of patients with respiratory acidosis (PaCO2 >6.3 kPa and pH <7.35) and the degree of acidosis measured on arrival to hospital compared to patients receiving standard care.
• To determine whether a prehospital titrated oxygen strategy for AECOPD patients reduces mortality (24 hours, 7 days, 30 days), acidosis, intensive care unit (ICU) admission rate, and need for assisted ventilation compared to patients receiving standard care, analyzed on a subgroup level based on prehospital transport time.
• To determine whether a titrated oxygen strategy has an effect on time to intensive care admission, non-invasive ventilation, or endotracheal assisted ventilation events compared with standard care.
• To determine if a titrated oxygen strategy will lower the readmission rate compared with standard care.
• To determine whether a prehospital titrated oxygen strategy for patients with AECOPD will result in reduced length of hospital and ICU stay compared with patients receiving standard care.

The clinical trial focuses on patients with **Acute Exacerbation of Chronic Obstructive Pulmonary Disease** (AECOPD). The study population includes both male and female participants over the age of 40, with a confirmed suspicion of COPD and a need for inhaled bronchodilators. The trial involves a vulnerable population, as indicated by the inclusion of individuals who may require special considerations. Participants were selected based on the treating EMT or Paramedic's suspicion of AECOPD. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of prehospital titrated oxygen therapy in patients with suspected **acute exacerbation of chronic obstructive pulmonary disease** (AECOPD) compared to standard care. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the healthcare providers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence recruitment on March 1, 2025, and conclude by March 30, 2028, with the primary objective of reducing 30-day mortality rates among the participants.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as confirmed suspicion of **COPD**, age over 40 years, and the need for inhaled bronchodilators. Following the initial screening, participants will be randomly assigned to receive either the investigational treatment or standard care. The study will include follow-up visits to monitor the participants' health status and treatment efficacy, with assessments of primary and secondary endpoints such as 24-hour, 7-day, and 30-day mortality, length of hospitalization, and ICU admission rates.

The expected duration of participant involvement is up to 30 days, with conditions for early termination including withdrawal of consent or any adverse events that may compromise participant safety. The trial will utilize **salbutamol sulfate**, **fenoterol hydrobromide**, **ipratropium bromide**, **oxygen**, and **medicinal air** as part of the treatment regimen, administered via inhalation or inhalation gas, in accordance with their marketing authorizations. The study is classified as low-intervention, as the investigational and auxiliary medicinal products are used within the terms of their marketing authorizations.

The clinical trial involves the administration of **Salbutamol** "TEVA", a nebuliser solution containing **salbutamol sulfate** as the active substance. This medication is provided in the form of an inhalation solution for use with a nebuliser. The maximum daily dose is 25 mg, with a total treatment period of one day. The solution is administered via inhalation, and participant compliance is monitored to ensure adherence to the dosing schedule. The product is manufactured by TEVA B.V and is not a paediatric formulation.

Another treatment used in the trial is **Berodual**, a nebuliser solution containing two active substances: **fenoterol hydrobromide** and **ipratropium bromide**. This medication is also administered as an inhalation solution via a nebuliser. The maximum daily dose is 6.25 mg, with a treatment period of one day. The solution is inhaled, and compliance is monitored to ensure proper administration. Berodual is produced by Boehringer Ingelheim International GmbH and is not formulated for paediatric use.

**Medicinsk Oxygen** "Air Liquide" 100% is used as an auxiliary treatment in the trial. It is a compressed medicinal gas with **oxygen** as the active substance. The maximum daily dose is 2500 litres, administered via inhalation gas, with a treatment period of one day. The product is manufactured by Air Liquide Sante International and is not a paediatric formulation. Compliance with the administration schedule is monitored throughout the trial.

Additionally, **Medicinsk Luft** "Air Liquide" 100% is included as a comparator treatment. This is a compressed medicinal gas containing **air, medicinal** as the active substance. The maximum daily dose is 2500 litres, administered via inhalation gas, with a treatment period of one day. The product is also manufactured by Air Liquide Sante International and is not intended for paediatric use. Participant compliance is monitored to ensure adherence to the dosing regimen.

Efficacy in the clinical trial titled "STOP-COPD Standard vs Targeted Oxygen Therapy Prehospital for Chronic Obstructive Pulmonary Disease" will be assessed using both primary and secondary endpoints. The primary endpoint is the **30-day mortality** rate, which will be used to determine the effectiveness of prehospital titrated oxygen therapy compared to standard care in patients with suspected acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Secondary endpoints include 24-hour mortality, 7-day mortality, length of hospitalization, ICU admission rate, length of ICU admission, and the need for non-invasive ventilation (NIV) and invasive mechanical ventilation within 24 hours, 7 days, and 30 days. Additional secondary endpoints involve the time to NIV and invasive ventilation, the proportion of patients with respiratory acidosis upon hospital arrival, the degree of acidosis based on pH-value, patient-reported dyspnea on a verbal rating scale from 0 to 10, readmission rate, and time to readmission.

The collection and analysis of these efficacy parameters will be conducted at specified timepoints, including 24 hours, 7 days, and 30 days post-intervention. The trial will utilize validated scales and laboratory tests to measure these outcomes, ensuring the reliability and accuracy of the data collected. The study is designed to evaluate whether the targeted oxygen therapy can reduce mortality and improve clinical outcomes in the specified patient population.