Clinical trial NCT05045612: Antibiotic Therapy in Viral Airway Infections
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Infectious Disease
Influenza
Respiratory Syncytial Virus (RSV)
Respiratory Tract Infections
Keywords: pragmatic trial
antibiotic stewardship
viral respiratory tract infection
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2021-09-16
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm, open label, pragmatic randomized controlled non-inferiority stop trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Early clinical response
timeFrame: 120 hours after randomization
Secondary outcomes:
measure: In-hospital mortality
timeFrame: Untill hospital discharge (commonly 3-5 days)
measure: 30-day mortality
timeFrame: 30 days after hospital discharge
measure: Duration of hospital admission
timeFrame: Untill hospital discharge (commonly 3-5 days)
measure: Antimicrobial days of therapy
timeFrame: Untill hospital discharge (commonly 3-5 days)
measure: Rescue antibiotic therapy during hospital admission
timeFrame: Untill hospital discharge (commonly 3-5 days)
measure: New antibiotic therapy for presumed airway infection
timeFrame: 30 days after hospital discharge
measure: 30-day readmission rate
timeFrame: 30 days after hospital discharge
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Drammen
country: Norway
facility: Drammen Hospital, Vestre Viken Hospital Trust
city: Gjettum
country: Norway
facility: Bærum Hospital, Vestre Viken Hospital Trust
city: Grålum
country: Norway
facility: Sykehuset Østfold HF
city: Kristiansand
country: Norway
facility: Sørlandet sykehus HF
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, Ullevål
city: Skien
country: Norway
facility: Telemark Hospital Trust
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North Norway
city: Trondheim
country: Norway
facility: St. Olavs hospital
city: Tønsberg
country: Norway
facility: Sykehuset i Vestfold HF
Study officials:
affiliation: University Hospital, Akershus
name: Magnus N Lyngbakken, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: