Antibiotic Therapy in Viral Airway Infections

NCT ID: NCT05045612

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-13
• Study Completion Date: 2029-11-30

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.

Conditions

Infectious Disease; Influenza; Respiratory Syncytial Virus (RSV); Respiratory Tract Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Stop antibiotic therapy as instituted by admitting physician

Group Type: EXPERIMENTAL

Stop antibiotic therapy

Intervention Type: OTHER

Stop antibiotic therapy instituted by the admitting physician

Control

Continue antibiotic therapy at the discretion of the treating physician (no change in ongoing treatment)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Stop antibiotic therapy

Stop antibiotic therapy instituted by the admitting physician

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oslo

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: lead

Responsible Party

Magnus Nakrem Lyngbakken

Postdoctoral fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Magnus N Lyngbakken, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Akershus

Locations

Haukeland University Hospital

Bergen, , Norway

Site Status: NOT_YET_RECRUITING

Drammen Hospital, Vestre Viken Hospital Trust

Drammen, , Norway

Site Status: RECRUITING

Bærum Hospital, Vestre Viken Hospital Trust

Gjettum, , Norway

Site Status: NOT_YET_RECRUITING

Sykehuset Østfold HF

Grålum, , Norway

Site Status: RECRUITING

Sørlandet sykehus HF

Kristiansand, , Norway

Site Status: RECRUITING

Akershus University Hospital

Lørenskog, , Norway

Site Status: RECRUITING

Oslo University Hospital, Ullevål

Oslo, , Norway

Site Status: RECRUITING

Telemark Hospital Trust

Skien, , Norway

Site Status: NOT_YET_RECRUITING

Stavanger University Hospital

Stavanger, , Norway

Site Status: RECRUITING

University Hospital of North Norway

Tromsø, , Norway

Site Status: RECRUITING

St. Olavs hospital

Trondheim, , Norway

Site Status: NOT_YET_RECRUITING

Sykehuset i Vestfold HF

Tønsberg, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Magnus N Lyngbakken, MD PhD

Role: CONTACT

magnus.lyngbakken@medisin.uio.no

+4793408837

Olav Dalgard, MD PhD

Role: CONTACT

olav.dalgard@medisin.uio.no

+4792616800

Facility Contacts

Dagfinn L Markussen, MD

Role: primary

dagfinn.lunde.markussen@helse-bergen.no

+4799270071

Karl Erik Müller, MD PhD

Role: primary

kamull@vestreviken.no

+4797501475

Helene Hestmann, MD

Role: primary

HHESTM@vestreviken.no

+4741610490

Sara F Debes, MD PhD

Role: primary

Sara.Foss.Debes@so-hf.no

Hans K Fløystad, MD

Role: primary

hans.kristian.floystad@sshf.no

+4797648526

Magnus N Lyngbakken, MD PhD

Role: primary

magnus.lyngbakken@medisin.uio.no

+4793408837

Kristian Tonby, MD PhD

Role: primary

kritonby@ous-hf.no

+4741550565

Marjut A Sarjomaa, MD

Role: primary

SARM@sthf.no

+4746660906

Åse G Riis, MD

Role: primary

ase.garlov.riis@sus.no

+4745217123

Vegard Skogen, MD PhD

Role: primary

vegard.skogen@unn.no

+4791364541

Jan Kristian Damås, MD PhD

Role: primary

jan.k.damas@ntnu.no

+4791112046

Asgeir Johannessen, MD PhD

Role: primary

asgeir.johannessen@siv.no

+4797983264

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021-004248-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

213847

Identifier Type: -

Identifier Source: org_study_id