Evaluation of Antibiotic Discontinuation in Adult Patients with Viral Respiratory Tract Infections: A Randomized Controlled Trial

The primary objective of the study titled "Antibiotic THErapy iN vIral Airway iNfections (ATHENIAN)" is to assess the safety and non-inferiority of discontinuing **antibiotic therapy** in adult patients with a positive airway sample for respiratory viruses, compared to the continuation of antibiotic therapy. This objective is clinically relevant as it addresses the potential overuse of antibiotics in cases of **viral respiratory tract infection**, which can contribute to antibiotic resistance and unnecessary side effects. The study aims to provide evidence on whether stopping antibiotics in such cases is a safe practice, potentially leading to changes in clinical guidelines and reducing the misuse of antibiotics.

The clinical trial involves **hospitalized** adults aged 18 years or older, both male and female, who are experiencing a **viral respiratory tract infection**. The study population is characterized by individuals with moderately severe disease, as indicated by a CRB65 score of 2 or less at the time of inclusion. Participants must have a nasopharyngeal swab positive for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), or human metapneumovirus (hMPV). All participants are on antibiotic therapy as initiated by the receiving physician from the emergency department. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, including the requirement for signed informed consent in accordance with ICH GCP and national/local regulations. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of discontinuing **antibiotic** therapy in adult patients with **viral respiratory tract infection**. This is an open-label, randomized, controlled, pragmatic trial. The primary objective is to assess whether discontinuation of antibiotic therapy is safe and non-inferior to its continuation in patients with a positive airway sample for respiratory viruses. The trial is expected to run from December 2021 to May 2027, with a maximum treatment period of 12 weeks for each participant.

Participants will be randomly assigned to either continue or discontinue antibiotic therapy. The trial will include several key visits: an inclusion (screening) visit, follow-up visits, and an end-of-study visit. During the inclusion visit, eligibility will be confirmed based on criteria such as being hospitalized, aged 18 years or older, having moderately severe disease, and a positive nasopharyngeal swab for specific viruses. Informed consent will be obtained according to ICH GCP and national regulations. Follow-up visits will monitor the primary endpoint, which is the early clinical response assessed at 120 hours post-randomization, defined as survival with symptom improvement without the need for rescue antibacterial therapy. Secondary endpoints include in-hospital mortality, mortality at 30 days, duration of hospital admission, days of antibiotic therapy, and hospital readmissions up to 30 days post-discharge.

The expected length of participant involvement is up to 30 days post-discharge, with conditions for early termination including withdrawal of consent or adverse events. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results. Participants will be monitored closely throughout the study to ensure their safety and well-being.

The clinical trial involves the use of several **antibiotic** treatments, each with distinct characteristics. The first experimental medication is classified under the **ATC code J01C**, which corresponds to **beta-lactam antibacterials, penicillins**. This medication is administered in a pharmaceutical form identified as **PHF00231MIG**. The route of administration is specified as "other use," and the treatment period is limited to a maximum of 12 weeks. The dosage and frequency of administration are not specified, and participant compliance will be monitored throughout the trial.

Another experimental treatment in the trial is categorized under **ATC code J01EA**, representing **trimethoprim and derivatives**. This medication is provided in the pharmaceutical form **PHF00245MIG** and is also administered via "other use." The treatment duration is similarly capped at 12 weeks, with no specific dosage or frequency details provided.

The trial also includes a medication under **ATC code J01GB**, which pertains to **other aminoglycosides**. This treatment is available in the pharmaceutical form **PHF00230MIG** and follows the same administration route of "other use." The maximum treatment period remains 12 weeks, with unspecified dosage and frequency.

Additionally, the study utilizes a treatment classified under **ATC code J01A**, known as **tetracyclines**. The pharmaceutical form for this medication is **PHF00006MIG**, and it is administered through "other use." The treatment period is restricted to 12 weeks, with no detailed dosage or frequency information.

Another medication involved in the trial is identified by **ATC code J01D**, which includes **other beta-lactam antibacterials**. This treatment is provided in the form **PHF00009MIG** and administered via "other use." The maximum treatment duration is 12 weeks, with dosage and frequency not specified.

The trial also incorporates a treatment under **ATC code J01MA**, representing **fluoroquinolones**. This medication is available in the pharmaceutical form **PHF00082MIG** and follows the "other use" administration route. The treatment period is limited to 12 weeks, with no specific dosage or frequency details.

Furthermore, the study includes a medication classified under **ATC code J01FF**, which pertains to **lincosamides**. This treatment is provided in the form **PHF00006MIG** and administered through "other use." The maximum treatment period is 12 weeks, with unspecified dosage and frequency.

Lastly, the trial involves a treatment under **ATC code J01X**, which includes **other antibacterials**. This medication is available in the pharmaceutical form **PHF00006MIG** and follows the "other use" administration route. The treatment duration is capped at 12 weeks, with no detailed dosage or frequency information provided.

The efficacy of the clinical trial titled "Antibiotic THErapy iN vIral Airway iNfections (ATHENIAN)" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the early clinical response, which will be evaluated at 120 hours post-randomization. This response is defined as survival with symptom improvement without the need for rescue antibacterial therapy. Secondary endpoints include in-hospital mortality, mortality at 30 days, duration of hospital admission, days of therapy with antibiotics, rescue antibiotic therapy during hospital admission, new antibiotic therapy for presumed airway infection up to 30 days after discharge, and hospital readmissions up to 30 days after discharge.

The trial aims to determine whether discontinuation of antibiotic therapy in patients with a positive airway sample for respiratory viruses is safe and non-inferior to the continuation of antibiotic therapy. The assessment of these endpoints will provide comprehensive data on the efficacy and safety of the intervention. The trial is designed as an open-labelled randomized controlled pragmatic trial, and the efficacy parameters will be collected and analyzed according to the predefined schedule and methods outlined in the trial protocol.