We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antibiotic Therapy in Viral Airway Infections (ATHENIAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05045612
Recruitment Status : Recruiting
First Posted : September 16, 2021
Last Update Posted : June 21, 2022
Sponsor:
Collaborator:
University of Oslo
Information provided by (Responsible Party):
Magnus Nakrem Lyngbakken, University Hospital, Akershus

Tracking Information
First Submitted Date  ICMJE September 7, 2021
First Posted Date  ICMJE September 16, 2021
Last Update Posted Date June 21, 2022
Actual Study Start Date  ICMJE January 13, 2022
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2021)
Early clinical response [ Time Frame: 120 hours after hospital admission ]
Survival with symptom improvement without receipt of rescue antibacterial therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2021)
  • In-hospital mortality [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Mortality during hospital admission
  • 30-day mortality [ Time Frame: 30 days after hospital discharge ]
    Mortality at 30 days after hospital discharge
  • Duration of hospital admission [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Duration of hospital admission
  • Antimicrobial days of therapy [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Number of days on antibiotic therapy
  • Rescue antibiotic therapy during hospital admission [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Rescue antibiotic therapy given to patients randomized to intervention
  • New antibiotic therapy for presumed airway infection [ Time Frame: 30 days after hospital discharge ]
    New antibiotic therapy instituted after hospital discharge
  • 30-day readmission rate [ Time Frame: 30 days after hospital discharge ]
    Hospital readmissions up to 30 days after hospital discharge
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2021)
  • In-hospital mortality [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Mortality during hospital admission
  • 30-day mortality [ Time Frame: 30 days after hospital discharge ]
    Mortality at 30 days after hospital discharge
  • Duration of hospital admission [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Duration of hospital admission
  • Defined daily doses of antibiotic therapy [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Number of daily doses of antibiotics given during hospital admission
  • Rescue antibiotic therapy during hospital admission [ Time Frame: Untill hospital discharge (commonly 3-5 days) ]
    Rescue antibiotic therapy given to patients randomized to intervention
  • New antibiotic therapy for presumed airway infection [ Time Frame: 30 days after hospital discharge ]
    New antibiotic therapy instituted after hospital discharge
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antibiotic Therapy in Viral Airway Infections
Official Title  ICMJE 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
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 hospital admission, 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 hospital admission 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two-arm, open label, pragmatic randomized controlled non-inferiority stop trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Infectious Disease
  • Influenza
  • Respiratory Syncytial Virus (RSV)
  • Respiratory Tract Infections
Intervention  ICMJE Other: Stop antibiotic therapy
Stop antibiotic therapy instituted by the admitting physician
Study Arms  ICMJE
  • Experimental: Intervention
    Stop antibiotic therapy as instituted by admitting physician
    Intervention: Other: Stop antibiotic therapy
  • No Intervention: Control
    Continue antibiotic therapy at the discretion of the treating physician (no change in ongoing treatment)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 7, 2021)
380
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2029
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Magnus N Lyngbakken, MD PhD +4793408837 magnus.lyngbakken@medisin.uio.no
Contact: Olav Dalgard, MD PhD +4792616800 olav.dalgard@medisin.uio.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05045612
Other Study ID Numbers  ICMJE 213847
2021-004248-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Magnus Nakrem Lyngbakken, University Hospital, Akershus
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Akershus
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University of Oslo
Investigators  ICMJE
Principal Investigator: Magnus N Lyngbakken, MD PhD University Hospital, Akershus
PRS Account University Hospital, Akershus
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP