Antibiotic Therapy in Viral Airway Infections

Официальное название

Antibiotic Therapy in Viral Airway Infections: An Open Labeled Randomized Controlled Pragmatic Trial to Evaluate the Efficacy and Safety of Discontinuing Antibiotic Therapy in Adult Patients With Respiratory Viruses

Обзор

Antimicrobial resistance is one of the most urgent health threats of our time, and Norwegian hospitals were required to reduce the use of broad-spectrum antibiotics with 30% by the end of 2020. In the current proposal, the investigators aim to assess the efficacy and safety of early discontinuation of antibiotic therapy in adult patients infected with respiratory viruses. A general recommendation to treat all instances of community acquired pneumonia (CAP) patients with antibiotics leads to significant antibiotic overtreatment. In 2008, the US Food and Drug Administration approved the first multiplex polymerase chain reaction assay for the detection of multiple respiratory virus nucleic acids simultaneously. The wide availability of such nucleic acid amplification tests (NAAT) for rapid viral detection together with chest radiographs has the potential to define patients who can be managed without antibiotics. Akershus University Hospital is one of the largest hospitals in Norway, with a catchment area of more than 550,000 people. In 2012 to 2013, the majority of patients admitted to Akershus University Hospital with suspected CAP and a positive viral NAAT were treated with antibiotics, a prescription pattern representing antibiotic overtreatment. The investigators accordingly hypothesize that discontinuation of antibiotic therapy in patients with moderately severe disease and airway sample positive for respiratory viruses is safe and non-inferior to continuation of antibiotic therapy.

Подробное описание

In patients with positive airway sample for respiratory viruses, the investigators hypothesize that discontinuation of antibiotic therapy is safe and non-inferior to continuation of antibiotic therapy. More specifically, the investigators hypothesize that the early clinical response assessed at 120 hours after randomization, defined as survival with symptom improvement without receipt of rescue antibacterial therapy, will be similar between patients who discontinue and continue antibiotic therapy. Furthermore, the investigators hypothesize that discontinuation of antibiotic therapy is associated with similar mortality rates, duration of hospital admission and reduced number of defined daily doses of antibiotics.

The primary aim is to assess whether discontinuation of antibiotic therapy in patients with positive airway sample for respiratory viruses is safe and associated with early clinical response assessed at 120 hours after randomization that is comparable to patients who continue antibiotic therapy.

The secondary aims are to assess whether discontinuation of antibiotic therapy in patients with positive airway sample for respiratory viruses is associated comparable (1) mortality rates, (2) duration of hospital admission, (3) defined daily doses of antibiotic therapy.

Specific objectives In patients with positive airway sample for respiratory viruses, assess the impact of discontinuing antibiotic therapy on early clinical response quantified as survival with symptom improvement without receipt of rescue antibacterial therapy. Early clinical response is defined as improvement of one or more levels relative to baseline in two or more symptoms of the investigator's assessment of symptoms of community-acquired bacterial pneumonia and no worsening of one or more levels in other symptoms.

Вмешательства

• Другое Stop antibiotic therapy
  Stop antibiotic therapy instituted by the admitting physician

Первичные конечные точки

• Early clinical response [Срок оценки: 120 hours after randomization]

Вторичные конечные точки (7)

• In-hospital mortality [Срок оценки: Untill hospital discharge (commonly 3-5 days)]
• 30-day mortality [Срок оценки: 30 days after hospital discharge]
• Duration of hospital admission [Срок оценки: Untill hospital discharge (commonly 3-5 days)]
• Antimicrobial days of therapy [Срок оценки: Untill hospital discharge (commonly 3-5 days)]
• Rescue antibiotic therapy during hospital admission [Срок оценки: Untill hospital discharge (commonly 3-5 days)]
• New antibiotic therapy for presumed airway infection [Срок оценки: 30 days after hospital discharge]
• 30-day readmission rate [Срок оценки: 30 days after hospital discharge]

Критерии участия

Критерии включения

• Hospitalized
• Adults 18 year or older
• Moderately severe disease (CRB65 ≤ 2 at time of inclusion)
• Nasopharyngeal swab positive for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV) or human metapneumovirus (hMPV)
• On antibiotic therapy as instituted by the receiving physician from the emergency department
• Signed informed consent must be obtained and documented according to ICH GCP, and national/local regulations.

Критерии исключения

• Requiring ICU admission at screening
• Requiring high-flow oxygen therapy or non-invasive ventilation at screening
• Signs of severe pneumonia (abscesses, massive pleural effusion, a well-defined lobar infiltrate on chest X-ray strongly suggestive of bacterial etiology)
• Not immunocompetent (i.e. on active chemotherapy, corticosteroid therapy equaling ≥ 20 mg prednisolone daily for ≥ 4 weeks, chronic immunosuppression due to solid organ transplant)
• SARS-CoV-2 positive
• Bacteremia
• Urine antigen test positive for legionella
• Any other infection necessitating antibiotic treatment
• Antibiotic use for assumed airway infection within the last 24 hours before admission to hospital
• Time from initiation of antibiotic therapy to screening >48 hours

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Норвегия · 12 центров

• Haukeland University Hospital — Bergen
• Drammen Hospital, Vestre Viken Hospital Trust — Drammen
• Bærum Hospital, Vestre Viken Hospital Trust — Gjettum
• Sykehuset Østfold HF — Grålum
• Sørlandet sykehus HF — Kristiansand
• Akershus University Hospital — Lørenskog
• Oslo University Hospital, Ullevål — Oslo
• Telemark Hospital Trust — Skien
• … и ещё 4 центра

Публикации

• Hovind MJ, Berdal JE, Benth JS, Dalgard O, Lyngbakken MN. Antibiotic therapy in viral airway infections (ATHENIAN): study protocol for an open labeled randomized controlled pragmatic trial to evaluate the efficacy and safety of discontinuing antibiotic therapy in adult patients infected with respiratory viruses. Trials. 2026 Apr 21;27(1):410. doi: 10.1186/s13063-026-09730-3. PMID 42015169

Идентификаторы

NCT: NCT05045612 · 213847 · 2021-004248-11

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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