Antibiotic Therapy in Viral Airway Infections

Influenza Clinical Trial

— ATHENIAN  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05045612
• Other study ID #: 213847
• Secondary ID: 2021-004248-11
• Status: Recruiting
• Phase: Phase 4
• Start date: January 13, 2022
• Est. completion date: November 2029

Study information

• Verified date: April 2024
• Source: University Hospital, Akershus
• Contact: Magnus N Lyngbakken, MD PhD
• Phone: +4793408837
• Email: magnus.lyngbakken[@]medisin.uio.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: November 2029
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Infectious Disease
• Influenza
• Respiratory Syncytial Virus (RSV)
• Respiratory Tract Infections

Intervention

Other:
• Stop antibiotic therapy
Stop antibiotic therapy instituted by the admitting physician

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen
Norway	Drammen Hospital, Vestre Viken Hospital Trust	Drammen
Norway	Sykehuset Østfold HF	Grålum
Norway	Akershus University Hospital	Lørenskog
Norway	Oslo University Hospital, Ullevål	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	Sykehuset i Vestfold HF	Tønsberg
Norway	University Hospital of North Norway	Tromsø
Norway	St. Olavs hospital	Trondheim

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Akershus	University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early clinical response	Survival with symptom improvement without receipt of rescue antibacterial therapy	120 hours after randomization
Secondary	In-hospital mortality	Mortality during hospital admission	Untill hospital discharge (commonly 3-5 days)
Secondary	30-day mortality	Mortality at 30 days after hospital discharge	30 days after hospital discharge
Secondary	Duration of hospital admission	Duration of hospital admission	Untill hospital discharge (commonly 3-5 days)
Secondary	Antimicrobial days of therapy	Number of days on antibiotic therapy	Untill hospital discharge (commonly 3-5 days)
Secondary	Rescue antibiotic therapy during hospital admission	Rescue antibiotic therapy given to patients randomized to intervention	Untill hospital discharge (commonly 3-5 days)
Secondary	New antibiotic therapy for presumed airway infection	New antibiotic therapy instituted after hospital discharge	30 days after hospital discharge
Secondary	30-day readmission rate	Hospital readmissions up to 30 days after hospital discharge	30 days after hospital discharge