Antibiotic THErapy iN vIral Airway iNfections (ATHENIAN): An open labelled randomized controlled pragmatic trial to evaluate the efficacy and safety of discontinuing antibiotic therapy in adult patients infected with respiratory viruses

2023-509286-20-00 Therapeutic use (Phase IV) Ongoing, recruiting

Start 15 May 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 12 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 400
Countries 1
Sites 12

Viral respiratory tract infection

In patients with positive airway sample for respiratory viruses, assess whether discontinuation of antibiotic therapy is safe and non-inferior to continuation of antibiotic therapy

Key facts

Sponsor
Akershus University Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Virus Diseases [C02]
Trial duration
15 May 2024 → ongoing
Decision date (initial)
2024-05-15
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2023-509286-20-00
EudraCT number
2021-004248-11
ClinicalTrials.gov
NCT05045612

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

In patients with positive airway sample for respiratory viruses, assess whether discontinuation of antibiotic therapy is safe and non-inferior to continuation of antibiotic therapy

Conditions and MedDRA coding

Viral respiratory tract infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Hospitalized
  2. Adults 18 year or older
  3. Moderately severe disease (CRB65 ≤ 2 at time of inclusion)
  4. Nasopharyngeal swab positive for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV) or human metapneumovirus (hMPV)
  5. On antibiotic therapy as instituted by the receiving physician from the emergency department
  6. Signed informed consent must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion criteria 10

  1. Requiring ICU admission at screening
  2. Requiring high-flow oxygen therapy or non-invasive ventilation at screening
  3. Signs of severe pneumonia (abscesses, massive pleural effusion, a well-defined lobar infiltrate on chest X-ray strongly suggestive of bacterial etiology)
  4. Not immunocompetent (i.e. on active chemotherapy, corticosteroid therapy equaling ≥ 20 mg prednisolone daily for ≥ 4 weeks, chronic immunosuppression due to solid organ transplant)
  5. SARS-CoV-2 positive
  6. Bacteremia
  7. Urine antigen test positive for legionella
  8. Any other infection necessitating antibiotic treatment
  9. Antibiotic use for assumed airway infection within the last 24 hours before admission to hospital
  10. Time from initiation of antibiotic therapy to screening >48 hours

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Early clinical response assessed at 120 hours after randomization, defined as survival with symptom improvement without receipt of rescue antibacterial therapy

Secondary endpoints 7

  1. In-hospital mortality
  2. Mortality at 30 days
  3. Duration of hospital admission
  4. Days of therapy with antibiotics
  5. Rescue antibiotic therapy during hospital admission
  6. New antibiotic therapy for presumed airway infection up to 30 days after discharge
  7. Hospital readmissions up to 30 days after discharge

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

-

J01C · Product

Pharmaceutical form
-
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01C — BETA-LACTAM ANTIBACTERIALS, PENICILLINS
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01A · Product

Pharmaceutical form
-
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01A — TETRACYCLINES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01FF · Product

Pharmaceutical form
PHF00006MIG
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01FF — LINCOSAMIDES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01MA · Product

Pharmaceutical form
PHF00082MIG
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01MA — FLUOROQUINOLONES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01GB · Product

Pharmaceutical form
PHF00230MIG
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01GB — OTHER AMINOGLYCOSIDES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01EA · Product

Pharmaceutical form
PHF00245MIG
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01EA — TRIMETHOPRIM AND DERIVATIVES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01X · Product

Pharmaceutical form
-
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01X — OTHER ANTIBACTERIALS
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

-

J01D · Product

Pharmaceutical form
-
Route of administration
OTHER USE
Max daily dose
0
Max total dose
0
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
J01D — OTHER BETA-LACTAM ANTIBACTERIALS
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Akershus University Hospital

9 Total trials 4 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Akershus University Hospital
Address
Sykehusveien 25
City
Loerenskog
Postcode
1474
Country
Norway

Scientific contact point

Organisation
Akershus University Hospital
Contact name
Department of infectious diseases

Public contact point

Organisation
Akershus University Hospital
Contact name
Department of infectious diseases

Locations

1 EU/EEA country · 12 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ongoing, recruiting 400 12
Rest of world — 0 —

Investigational sites

Norway

12 sites · Ongoing, recruiting
Vestre Viken HF
Department of Internal Medicine, Sogneprest Munthe-Kaas Vei 100, 1346, Gjettum
Vestre Viken HF
Department of Internal Medicine, Groenland 32, 3045, Drammen
Haukeland University Hospital
Emergency Care Clinic, Haukelandsveien 22, 5009, Bergen
Stavanger University Hospital HF
Department of Infectious Diseases, Helse Stavanger HF, Postboks 8100, Stavanger
Oslo University Hospital HF
Department of Infectious Diseases, P. O. Box 4950, 0424, Oslo
St. Olavs hospital HF
Department of Infectious Diseases, Postboks 3250, Torgarden, Trondheim
Akershus University Hospital
Department of Infectious Diseases, Sykehusveien 27, 1478, Lorenskog
University Hospital of North Norway
Department of Infectious Diseases, Postboks 100, 9038, Tromsø
Sørlandet sykehus Kristiansand
Department of Internal Medicine, Egsveien 100, 4615, Kristiansand
Østfold Hospital Trust
Center for Laboratory Medicine, Kalnesveien 300, 1714, Grålum
Sykehuset Telemark HF
Infection Control, Ulefossvegen 55, 3710, Skien
Vestfold Hospital Trust
Department of Infectious Diseases, Sykehuset i Vestfold HF, Postboks 2168, Tønsberg

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2024-05-15 2024-05-15

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) ATHENIAN_protokoll_v1.13_to_v1.14 1.14
Protocol (for publication) D1_Protocol 2023-509286-20-00 1.14
Recruitment arrangements (for publication) K1_Recruitment arrangements 2023-509286-20-00 1
Subject information and informed consent form (for publication) L1_SIS and ICF ATHENIAN 2023-509286-20-00 1.10
Subject information and informed consent form (for publication) SamtykkeATHENIAN_v13_to_v18_TC 1.8
Subject information and informed consent form (for publication) SamtykkeATHENIAN_v18_to_v19_TC 1.9
Subject information and informed consent form (for publication) SamtykkeATHENIAN_v19_to_v110_TC 1
Summary of Product Characteristics (SmPC) (for publication) ATHENIAN document for CTR transferral - IMP 1
Synopsis of the protocol (for publication) D1_Protocol synopsis NO 2023-509286-20-00 1

Application history

4 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-04-12 Norway Acceptable
2024-05-08
 2024-05-15
2 SUBSTANTIAL MODIFICATION SM-1 2024-08-08 Norway Acceptable
2024-09-27
 2024-09-30
3 SUBSTANTIAL MODIFICATION SM-3 2024-12-18 Norway Acceptable
2025-02-11
 2025-02-12
4 SUBSTANTIAL MODIFICATION SM-4 2025-05-12 Norway Acceptable
2025-07-04
 2025-07-09