AIR. ANTIBIOTIC THERAPY IN RESPIRATORY TRACT INFECTIONS A controlled randomized, open label, multicenter, non-inferiority trial evaluating an individualized antibiotic treatment duration based on patient clinical response, evaluated through connected devices, for suspected community acquired pneumonia in the community setting

2024-516097-30-00 Protocol P160929J Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 10 sites · Protocol P160929J

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 500
Countries 1
Sites 10

Community acquired pneumonia (CAP)

To demonstrate that stopping antibiotic treatment in patients diagnosed with acute CAP based on clinical response has a non-inferior efficacy 15 days after start of treatment, compared to a conventional predetermined duration left to the physician's judgement, in adults treated in the community setting

Key facts

Sponsor
Assistance Publique Hopitaux De Paris
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Respiratory Tract Diseases [C08]
Decision date (initial)
2024-11-13
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
French Ministry of Health (PHRC-N 2016)

External identifiers

EU CT number
2024-516097-30-00
EudraCT number
2019-001873-10
ClinicalTrials.gov
NCT04166110

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To demonstrate that stopping antibiotic treatment in patients diagnosed with acute CAP based on clinical response has a non-inferior efficacy 15 days after start of treatment, compared to a conventional predetermined duration left to the physician's judgement, in adults treated in the community setting

Secondary objectives 11

  1. Clinical success at late follow up (Day 30)
  2. Duration of antibiotic treatment
  3. Adverse events (frequency and severity)
  4. Patient's pneumonia symptoms and quality of life
  5. To study the relationship between the composition of the respiratory microbiome at the start of treatment and the response to antibiotic treatment
  6. To investigate the link between the composition of the respiratory microbiome at the start of treatment and clinical treatment failure (persistence of symptoms at TOC)
  7. To investigate the link between the composition of the respiratory microbiome at the start of treatment and pneumonia recurrence (second episode of pneumonia with at least one common pathogen) or relapse (second episode of pneumonia with new pathogens)
  8. To study the link between the composition of the respiratory microbiome at the start of treatment and the emergence of antibiotic resistance
  9. To study the link between the antibiotic regimen (spectrum and dose) and time course of the respiratory microbiome composition and resistome
  10. To study the link between the antibiotic regimen (spectrum and dose) and time course of the gut microbiome composition and resistome
  11. To evaluate the average duration of antimicrobial treatment according to the composition of the respiratory microbiome

Conditions and MedDRA coding

Community acquired pneumonia (CAP)

VersionLevelCodeTermSystem organ class
20.1 LLT 10010120 Community acquired pneumonia 10021881

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Patient aged 18 years or more
  2. Presenting with suspected CAP defined by the presence of at least 2 of the following diagnostic clinical criteria: Fever (temperature > 38°C), Dyspnea, Cough, Production of purulent sputum, Crackles, Radiological evidence of a new infiltrate (on chest X-ray or CT scan)
  3. In need for antibiotic treatment targeting respiratory tract, according to the physician in charge
  4. No other site of infection besides respiratory
  5. With home internet access (WIFI)
  6. Affiliated to health insurance
  7. Is able to take oral treatment
  8. Has given written informed consent

Exclusion criteria 19

  1. Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency)
  2. Hospitalization following consultation
  3. Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, immunosuppressive treatments or corticosteroids (prednisolone equivalent) > 10 mg/day, transplant, myeloma, lymphoma, known HIV and CD4<400/mm3, sickle-cell disease, Child-Pugh class C cirrhosis)
  4. Suspected or confirmed legionellosis
  5. Atrial fibrillation / constitutive tachycardia (usual heart rate > 100/min)
  6. Baseline oxygen saturation < 90%
  7. Home oxygen therapy
  8. More than 24 hours of antibiotics prior to consultation
  9. Any other infection necessitating concomitant antibiotic treatment
  10. Contraindications to the study antibiotics
  11. Concomitant steroid treatment only for patients treated with fluoroquinolones antibiotics
  12. Pre-existing aortic aneurysm or dissection, family history of aortic aneurysm or dissection, Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arthritis, uncontrolled arterial hypertension, atherosclerosis only for patients treated with fluoroquinolones antibiotics
  13. Pregnancy
  14. Breastfeeding
  15. Life expectancy < 1 month
  16. Patient under legal guardianship
  17. Homeless patient
  18. Patient unable to use the connected devices
  19. Patient enrolled in another interventional clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Percentage of cure at Day 15 after the start of treatment

Secondary endpoints 10

  1. Percentage of cure at Day 30
  2. Duration of antibiotic treatment
  3. Frequency and severity of adverse events between the 2 study arms
  4. Patients' evolution of pneumonia symptoms and quality of life between the 2 study arms
  5. A composite endpoint defined by the observation of one of the events characterizing the response to antibiotic treatment, among: clinical failure or; microbiological failure or; emergence of antibiotic resistance
  6. Time to clinical recovery (regardless of microbiological recovery or resistance failure)
  7. Presence or absence of antimicrobial resistance at any point during follow-up
  8. Association between specific antibiotics and respiratory microbiome evolution
  9. Association between specific antibiotics and gut microbiome evolution
  10. Duration of antimicrobial treatment

Investigational products

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

Test 11

Ofloxacin Hydrochloride

SCP111060923 · ATC

Active substance
Ofloxacin Hydrochloride
Route of administration
ORAL USE
Max daily dose
1 g gram(s)
Max total dose
14 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
J01MA12 — LEVOFLOXACIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ciprofloxacin Hydrochloride

SCP12479042 · ATC

Active substance
Ciprofloxacin Hydrochloride
Route of administration
ORAL USE
Max daily dose
1.5 g gram(s)
Max total dose
21 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
J01MA02 — CIPROFLOXACIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ofloxacin Hydrochloride

SCP128018 · ATC

Active substance
Ofloxacin Hydrochloride
Route of administration
ORAL USE
Max daily dose
800 mg milligram(s)
Max total dose
11.2 g gram(s)
Max treatment duration
14 Week(s)
Authorisation status
Authorised
ATC code
J01MA01 — OFLOXACIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Amoxicillin Sodium

SCP10330863 · ATC

Active substance
Amoxicillin Sodium
Route of administration
ORAL USE
Max daily dose
3 g gram(s)
Max total dose
42 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
J01CA04 — AMOXICILLIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Azithromycin

SCP1167043 · ATC

Active substance
Azithromycin
Substance synonyms
AZITROMICINA
Route of administration
ORAL USE
Max daily dose
500 mg milligram(s)
Max total dose
2.5 g gram(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
J01FA10 — AZITHROMYCIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Pristinamycin

SCP188790 · ATC

Active substance
Pristinamycin
Route of administration
ORAL USE
Max daily dose
3 g gram(s)
Max total dose
42 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
J01FG01 — PRISTINAMYCIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Demeclocycline Hydrochloride

SCP100375661 · ATC

Active substance
Demeclocycline Hydrochloride
Route of administration
ORAL USE
Max daily dose
1 g gram(s)
Max total dose
5 g gram(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
J01FA09 — CLARITHROMYCIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

—

SCP10357312 · ATC

Route of administration
ORAL USE
Max daily dose
3 g gram(s)
Max total dose
30 g gram(s)
Max treatment duration
10 Day(s)
Authorisation status
Authorised
ATC code
J01FA01 — ERYTHROMYCIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Amoxicillin Sodium

SCP109545371 · ATC

Active substance
Amoxicillin Sodium
Route of administration
ORAL USE
Max daily dose
3 g gram(s)
Max total dose
30 g gram(s)
Max treatment duration
10 Day(s)
Authorisation status
Authorised
ATC code
J01CR02 — AMOXICILLIN AND BETA-LACTAMASE INHIBITOR
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Moxifloxacin Hydrochloride

SCP1150651 · ATC

Active substance
Moxifloxacin Hydrochloride
Route of administration
ORAL USE
Max daily dose
400 mg milligram(s)
Max total dose
4 g gram(s)
Max treatment duration
10 Day(s)
Authorisation status
Authorised
ATC code
J01MA14 — MOXIFLOXACIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ampicillin Sodium

SCP106362797 · ATC

Active substance
Ampicillin Sodium
Route of administration
BUCCAL USE
Max daily dose
2 g gram(s)
Max total dose
48 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
J01CA01 — AMPICILLIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

251 Total trials 131 Recruiting 54 Ended
Academic / Non-commercial
Sponsor organisation
Assistance Publique Hopitaux De Paris
Address
Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City
Paris Cedex 10
Postcode
75475
Country
France

Scientific contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Coordinator Investigator

Public contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Coordinator Investigator

Locations

1 EU/EEA country · 10 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 500 10
Rest of world — 0 —

Investigational sites

France

10 sites · Authorised, recruitment pending
Cabinet médical IPSO Paris Ourcq
Medical Office, 151 rue Jean Jaures, 75019, Paris
Ma Maison Médicale - Saint-Cloud
Medical Office, 40 Rue Gounod, 92210, Saint-Cloud
Maison Médicale Chemin Vert
Medical Office, 6 rue du Chemin Vert, 75011, Paris
Maison de santé pluriprofessionnelle universitaire Jacques Prévert
Medical Office, 10 Place George Sand, 78180, Montigny-Le-Bretonneux
Cabinet médical IPSO Paris Italie
Medical Office, 153 avenue d’Italie, 75013, Paris
Cabinet médical IPSO Paris Nation
Medical Office, 73 rue de Montreuil, 75011, Paris
Cabinet médical IPSO Lyon Brotteaux
Medical Office, 12 bis Bd Jules Favre, 69006, Lyon
Cabinet Carré Notre-Dame
Medical Office, 10 Rue André Chénier, 78000, Versailles
Ipso Sante
Medical Office, 323 Rue Saint Martin, 75003, Paris
Cabinet médical IPSO Paris Richard Lenoir
Medical Office, 55 boulevard Richard Lenoir, 75011, Paris

Results and documents

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

Documents 18 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol addendum 2_Patient booklet and card_2024-516097-30-00 2.0
Protocol (for publication) D1_Protocol addendum 4_DM description_2024-516097-30-00 2.0
Protocol (for publication) D1_Protocol addendum 5_DM CE certificates_2024-516097-30-00_v2-0 2.0
Protocol (for publication) D1_Protocol_2024-516097-30-00 2.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS-ICF 2.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_amoxicilline 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_amoxicilline-acide-clavulanique 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_ampicilline 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_azithromycin 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_ciprofloxacine 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_clarithromycine 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_erythromycine 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_levofloxacine 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_moxifloxacine 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_ofloxacine 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_pristinamycine 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_2024-516097-30-00 2.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-15 France Acceptable
2024-11-06
 2024-11-13