Infectious DiseasePhase 4ATHENIANNCT05045612
Antibiotic Therapy in Viral Airway Infections
A Phase 4 study testing Stop antibiotic therapy in people with Infectious Disease and Influenza, run by University Hospital, Akershus at 12 sites in Norway.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infectious Disease, Influenza, Respiratory Syncytial Virus (RSV)
- What is being tested?
- Stop antibiotic therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 12 sitesNorway
- Study dates
- 13 Jan 2022to Nov 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Norway12 sites, 12 recruiting
- Not yet recruiting
Haukeland University Hospital
Bergen, 5021
Dagfinn L Markussen, MD, +4799270071, dagfinn.lunde.markussen@helse-bergen.no
- Recruiting
Drammen Hospital, Vestre Viken Hospital Trust
Drammen, 3004
Karl Erik Müller, MD PhD, +4797501475, kamull@vestreviken.no
- Not yet recruiting
Bærum Hospital, Vestre Viken Hospital Trust
Gjettum, 1346
Helene Hestmann, MD, +4741610490, HHESTM@vestreviken.no
- Recruiting
Sykehuset Østfold HF
Grålum, 1714
Sara F Debes, MD PhD, Sara.Foss.Debes@so-hf.no
- Recruiting
Sørlandet sykehus HF
Kristiansand
Hans K Fløystad, MD, +4797648526, hans.kristian.floystad@sshf.no
- Recruiting
Akershus University Hospital
Lørenskog, 1478
Magnus N Lyngbakken, MD PhD, +4793408837, magnus.lyngbakken@medisin.uio.no
- Recruiting
Oslo University Hospital, Ullevål
Oslo, 0424
Kristian Tonby, MD PhD, +4741550565, kritonby@ous-hf.no
- Not yet recruiting
Telemark Hospital Trust
Skien, 3710
Marjut A Sarjomaa, MD, +4746660906, SARM@sthf.no
- Recruiting
Stavanger University Hospital
Stavanger, 4068
Åse G Riis, MD, +4745217123, ase.garlov.riis@sus.no
- Recruiting
Sykehuset i Vestfold HF
Tønsberg, 3103
Asgeir Johannessen, MD PhD, +4797983264, asgeir.johannessen@siv.no
- Recruiting
University Hospital of North Norway
Tromsø, 9038
Vegard Skogen, MD PhD, +4791364541, vegard.skogen@unn.no
- Not yet recruiting
St. Olavs hospital
Trondheim, 7006
Jan Kristian Damås, MD PhD, +4791112046, jan.k.damas@ntnu.no
About this study
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
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.
Read the 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
- Being tested
- Stop antibiotic therapy
- Keywords
- pragmatic trial, antibiotic stewardship, viral respiratory tract infection
- Medical subject headings
- Communicable Diseases, Influenza, Human, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stop antibiotic therapyOther
Stop antibiotic therapy instituted by the admitting physician
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Stop antibiotic therapy as instituted by admitting physician Receives: Other: Stop antibiotic therapy |
| Control | No intervention | Continue antibiotic therapy at the discretion of the treating physician (no change in ongoing treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early clinical response
Survival with symptom improvement without receipt of rescue antibacterial therapy
Measured: 120 hours after randomization
Secondary outcomes (7)
In-hospital mortality
Mortality during hospital admission
Measured: Untill hospital discharge (commonly 3-5 days)
30-day mortality
Mortality at 30 days after hospital discharge
Measured: 30 days after hospital discharge
Duration of hospital admission
Duration of hospital admission
Measured: Untill hospital discharge (commonly 3-5 days)
Antimicrobial days of therapy
Number of days on antibiotic therapy
Measured: Untill hospital discharge (commonly 3-5 days)
Rescue antibiotic therapy during hospital admission
Rescue antibiotic therapy given to patients randomized to intervention
Measured: Untill hospital discharge (commonly 3-5 days)
New antibiotic therapy for presumed airway infection
New antibiotic therapy instituted after hospital discharge
Measured: 30 days after hospital discharge
30-day readmission rate
Hospital readmissions up to 30 days after hospital discharge
Measured: 30 days after hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2021
- Study start13 Jan 2022
- Primary completionMay 2027 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infectious DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm, open label, pragmatic randomized controlled non-inferiority stop trial
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo
- Responsible party
- Principal investigator, Magnus Nakrem Lyngbakken, University Hospital, Akershus
- Investigators
- Magnus N Lyngbakken, MD PhD, Principal investigator, University Hospital, Akershus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05045612
- Sponsor's protocol ID
- 213847
- Other IDs
- 2021-004248-11
- Acronym
- ATHENIAN
- Status last verified
- Aug 2025
- First submitted
- 7 Sep 2021
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 42015169
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05045612
- Acronym / sponsor ID
- ATHENIAN / 213847
- Conditions
- Infectious Disease, Influenza, Respiratory Syncytial Virus (RSV), Respiratory Tract Infections
- Keywords
- pragmatic trial, antibiotic stewardship, viral respiratory tract infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Collaborators
- University of Oslo
- Study start
- 13 Jan 2022 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Nov 2029 (estimated)
- First posted
- 16 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two-arm, open label, pragmatic randomized controlled non-inferiority stop trial
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Stop antibiotic therapyStop antibiotic therapy as instituted by admitting physician |
| Control | No intervention | –Continue antibiotic therapy at the discretion of the treating physician (no change in ongoing treatment) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stop antibiotic therapyStop antibiotic therapy instituted by the admitting physician | Other | Intervention |
Primary outcome
Early clinical response
Time frame: 120 hours after randomization
Survival with symptom improvement without receipt of rescue antibacterial therapy
7 secondary outcomes
In-hospital mortality
Time frame: Untill hospital discharge (commonly 3-5 days)
30-day mortality
Time frame: 30 days after hospital discharge
Duration of hospital admission
Time frame: Untill hospital discharge (commonly 3-5 days)
Antimicrobial days of therapy
Time frame: Untill hospital discharge (commonly 3-5 days)
Rescue antibiotic therapy during hospital admission
Time frame: Untill hospital discharge (commonly 3-5 days)
New antibiotic therapy for presumed airway infection
Time frame: 30 days after hospital discharge
30-day readmission rate
Time frame: 30 days after hospital discharge
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Derived from this study: PubMed 42015169Hovind 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Magnus N Lyngbakken, MD PhD principal investigator
University Hospital, Akershus
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Stop antibiotic therapy in people with Infectious Disease and Influenza, run by University Hospital, Akershus at 12 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Magnus N Lyngbakken, MD PhD (+4793408837, magnus.lyngbakken@medisin.uio.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early clinical response (time frame: 120 hours after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05045612, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.