Clinical trial NCT06291012: Stopping Pneumonia Antibiotherapy Regimen Early
Official title: Evaluation of a Therapeutic Strategy to Reduce the Duration of Antibiotic Therapy for Community-acquired Alveolar Pneumonia in Children: a Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Community-acquired Pneumonia
Child, Only
Keywords: Antibiotics management
Amoxicillin
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
First posted: 2024-03-04
Enrollment: 1100
Sex: ALL
Minimum age (years): 3
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The randomization will be carried out by minimization with stratification on the investigating center and age (\< 1 year and ≥ 1 year)
Primary purpose: TREATMENT

Brief summary: The hypothesis for this trial is that an antibiotic strategy for the management of non-severe community-acquired alveolar pneumonia in children aged 3 to 59 months, including amoxicillin 80-100 mg/kg/day for at least 3 days in case of rapid response and 5 days in case of delayed response, would not be inferior to current French recommendations (antibiotic therapy for 5 days in case of rapid response and 7 days in case of delayed response) in terms of treatment of failure rate at 7 days.

Detailed description: Introduction:

The World Health Organization (WHO) has declared antimicrobial resistance to be one of the 10 greatest threats to public health. As such, it has issued recommendations for children for the diagnosis and treatment of pneumonia with amoxicillin for 3 days. However, this strategy includes viral infections and therefore cannot be extrapolated directly to countries with a high level of access to healthcare, where the aim is to treat only bacterial pneumonia and for the shortest possible time to limit the emergence of resistant bacteria. Thus, our study proposes to use a definition of pneumonia adapted to countries with a high level of access to healthcare and to test an adaptive treatment regimen including a clinical reassessment at D3, which will propose a treatment limited to 3 days in case of rapid response and 5 days in case of delayed response.

Aim:

The aim of this trial is to demonstrate the non-inferiority of a strategy of antibiotic treatment with amoxicillin 80-100 mg/kg/day for 3 days in the case of a rapid response or 5 days in the case of a delayed response, versus antibiotic treatment for 5 days in the case of a rapid response or 7 days in the case of a delayed response for the management of non-severe community-acquired alveolar pneumonia in children between 3 and 59 months, in terms of the rate of treatment failure at 7 days.

Methods:

As the hypothesis is not that a shorter antibiotic regimen is more effective in this indication, a non-inferiority trial is the most appropriate design to assess whether this efficacy is broadly comparable with the reference regimen. The primary endpoint chosen is the one already used in an international clinical trial on this disease in children, which has been agreed upon.

In order to meet the objective of the study, 1100 patients will be included.

* At D0, patients will be included and randomized by the investigator, and will begin their treatment: Short arm: treatment by amoxicillin 80-100 mg/kg/d for 3 days if rapid response or 5 days if delayed response; or Long arm: treatment by amoxicillin 80-100 mg/kg/d for 5 days if rapid response or 7 days if delayed response. A prescription and follow-up diary will be given to the family.
* At D3, the doctor will assess the response to the treatment. If the response is assessed as rapid, then the investigator will reduce the duration of antibiotic treatment depending on the arm to which the child has been randomized. Parents will continue to complete the follow-up diary until D7.
* At the D7 visit, the investigator evaluates the primary endpoint and some of the secondary endpoints.
* At the D30 visit, the investigator assesses of last secondary endpoints.

Given the non-inferiority design, data will be analyzed on a per protocol basis for the primary analysis. The per-protocol population will be defined by radiologist of pneumonia diagnosis, at least one dose of amoxicillin, and having primary endpoint assessment data at 7 days. Non-inferiority will be declared if the lower bound of the confidence interval of the difference in failure rate between the 3-day and 5-day arms is less than 3.5%.

Eligibility criteria: Inclusion Criteria:

* Child with a diagnosis of community-acquired alveolar pneumonia defined as an association of 3 major criteria + at least 3/5 minor criteria:

  * Major criteria: Fever (\> 38°C), Polypnea and Chest x-ray
  * Minor criteria: Localized crackles, C-Reactive Protein (CRP) \> 80mg/L, Alteration of general condition, Cough and Pulmonary condensation syndrome.
* Child with an episode that began less than 7 days before inclusion, in the community.
* Absence of hospitalization criteria

Exclusion Criteria:

* Pre-existing underlying pathology: acquired or hereditary immune deficiencies, cardiac pathologies, chronic respiratory failure or pulmonary malformations, neurological or muscular diseases at risk of respiratory decompensation, serious chronic kidney diseases and nephrotic syndromes, sickle cell anemia, diabetes, chronic liver diseases, oncological pathologies and hematological, organ and hematopoietic stem cell transplants, inflammatory and/or autoimmune diseases receiving immunosuppressive treatment, people infected with HIV, obese people with a body mass index (BMI) ≥ the 97th percentile
* Asthma with basic treatment
* Wheezing during the episode
* Presence of pleural effusion on radiography
* Presence of toxin signs
* Antibiotic therapy within 48 hours before inclusion
* Anti-inflammatory therapy within 48 hours before inclusion
* Allergy or contraindication to penicillin
* History of more than 2 bacterial pneumonias per year
* Associated infection requiring more than 3 days of antibiotics
* Patient hospitalized within 15 days before inclusion
* Failure to obtain informed consent by the legal representative(s)
* Patient whose legal representatives are unable to read/write french language
* Patient not affiliated with or not benefiting from a national health insurance scheme
* Patient participating in another interventional research involving human person

Primary outcomes:
measure: Therapeutic failure rate D7
timeFrame: Day 7
Secondary outcomes:
measure: Therapeutic failure rate on D30
timeFrame: Day 30
measure: Adverse effects
timeFrame: Day 0, Day 3, Day 7 and Day 30
measure: Compliance
timeFrame: Day 7, or Day 30 in case of therapeutic failure
measure: Duration of antibiotic therapy
timeFrame: Day 7 and Day 30
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHU de Montpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Sarah DUTRON, MD
role: STUDY_DIRECTOR
References:
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