Evaluation of Multiplex PCR, Procalcitonin, and Sputum Appearance in Reducing Antibiotic Duration in Severe COPD Exacerbation with Cefotaxime and Drug Combination

The primary objective of this study is to evaluate the **effectiveness** in terms of antibiotic sparing of a personalized diagnostic and therapeutic strategy compared to a usual strategy during severe exacerbation of chronic obstructive pulmonary disease (EA-COPD) in the intensive care unit (ICU). This is clinically relevant as it aims to reduce the duration of antibiotic therapy, potentially minimizing antibiotic resistance and adverse effects associated with prolonged antibiotic use.

Secondary objectives include evaluating the effectiveness and safety of the tested strategy compared to a usual strategy. This assessment is crucial for determining the overall benefit-risk profile of the personalized approach in managing EA-COPD.

The clinical trial involves participants diagnosed with **chronic obstructive pulmonary disease** (COPD) experiencing acute exacerbations, specifically those requiring mechanical ventilation or high-flow nasal oxygen therapy. The study population includes both male and female subjects aged 18 years and older, with a history of smoking and confirmed COPD as per GOLD 2020 guidelines, regardless of the disease stage. Participants are required to have acute respiratory failure necessitating admission to the ICU. The trial does not focus on a vulnerable population, and all participants must be affiliated with a social security scheme. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the trial data. Key inclusion criteria include the ability to provide consent, either personally or through a relative, or inclusion in an emergency situation. The selection process for the trial population is not detailed in the provided data.

The clinical trial is designed to evaluate the effectiveness of a personalized diagnostic and therapeutic strategy in reducing antibiotic use during severe exacerbations of **chronic obstructive pulmonary disease** (COPD) in the intensive care unit (ICU). This study is a randomized, controlled, open-label, multicenter trial conducted in parallel groups. The trial aims to compare the personalized strategy against the usual care strategy, with the primary endpoint being the number of days alive without antibiotics by day 28. Secondary endpoints include the number of days with antibiotics, incidence rates of nosocomial pneumonia, and colonization with multi-resistant bacteria, among others, all assessed on day 28 and day 90.

The trial is expected to run from July 19, 2021, to February 24, 2025. Participants will be involved for a maximum treatment period of 7 days, with the possibility of early termination if they do not meet the inclusion criteria or if they experience adverse events that necessitate withdrawal. The inclusion criteria require participants to be 18 years or older, have post-smoking COPD confirmed according to GOLD 2020, and experience an acute exacerbation with acute respiratory failure requiring ICU admission and mechanical ventilation. Consent must be obtained from the patient or a relative, or inclusion must occur in an emergency situation.

Study visits will follow a structured sequence, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be conducted to monitor the primary and secondary endpoints, with the end-of-study visit occurring on day 28. The trial will utilize various antibiotics, including **cefotaxime**, **amoxicillin**, **piperacillin**, and **ciprofloxacin**, administered through different routes such as injection, intravenous, and oral, depending on the specific treatment arm. The trial is not categorized as low intervention and is conducted under phase 3, focusing on medications used within their marketing authorization.

The clinical trial involves the administration of several **antibiotics** to evaluate their effectiveness in reducing the duration of antibiotic therapy during severe exacerbations of chronic obstructive pulmonary disease (COPD). The experimental medication **Cefotaxime** is utilized in the form of a powder for solution for injection or infusion. It is administered via injection, with a treatment period not exceeding 7 days. The dosage is measured in milligrams, although specific dosing details are not provided. Participant compliance is monitored to ensure adherence to the administration schedule.

Another experimental medication, **Amoxicillin**, is used in two different pharmaceutical forms: as a powder for injection and as a tablet. The powder for injection is administered intravenously, while the tablet form is taken orally. Both forms have a maximum treatment period of 7 days, with dosing measured in milligrams. The study ensures that participants adhere to the prescribed dosing schedule through compliance monitoring.

The trial also includes the use of **Piperacillin Sodium and Tazobactam Sodium**, which are administered together as a combination therapy. This medication is provided in a parenteral form, with administration occurring through parenteral use. The treatment duration is limited to 7 days, and dosing is measured in milligrams. Compliance with the administration protocol is closely monitored.

**Spiramycin** is included in the study as a film-coated tablet, administered orally. The treatment period is capped at 7 days, with dosing measured in million international units. Participant adherence to the oral administration schedule is monitored to ensure compliance.

Lastly, **Ciprofloxacin** is administered as a film-coated tablet, taken orally. The treatment duration is restricted to 7 days, with dosing measured in milligrams. Compliance monitoring is implemented to ensure participants follow the prescribed oral dosing regimen.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the number of days alive without antibiotics on day 28 (D28). This endpoint will provide a direct measure of the effectiveness of the personalized diagnostic and therapeutic strategy in reducing antibiotic use during severe **Chronic Obstructive Pulmonary Disease (COPD)** exacerbations.

Secondary endpoints include the number of days with antibiotics in patients alive on D28, the number of days with broad-spectrum antibiotics in patients alive on D28, and the incidence rate of nosocomial pneumonia on day 28. Additional secondary endpoints are the incidence rate of colonization or infection with multi-resistant bacteria on day 28, duration of stay in the Intensive Care Unit (ICU) on D28, length of hospital stay on D28, and the number of days alive without mechanical ventilation on D28. Mortality rates in the ICU and hospital on day 28 and day 90, as well as the number of additional COPD exacerbations requiring hospitalization or systemic therapy by day 90, will also be evaluated. The time between the index COPD exacerbation and the next exacerbation requiring hospitalization or systemic therapy by day 90, along with the COPD Assessment Test (CAT) questionnaire at day 90, will further contribute to the assessment of efficacy.