Stopping Pneumonia Antibiotherapy Regimen Early

NCT ID: NCT06291012

Last Updated: 2024-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-01

Study Completion Date

2027-09-01

Brief Summary

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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

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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%.

Conditions

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Community-acquired Pneumonia Child, Only

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The randomization will be carried out by minimization with stratification on the investigating center and age (\< 1 year and ≥ 1 year)
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Caregivers

Study Groups

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Short arm

Antibiotic therapy for 3 to 5 days depending on response

Group Type EXPERIMENTAL

Quick response: Amoxicillin for 3 days

Intervention Type DRUG

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of rapid response\*: Immediate stop of antibiotherapy (after 9 complete doses)

\*A rapid response is determined by a favorable clinical evolution (MASCOT 2002 study)

Delayed response: Amoxicillin for 5 days

Intervention Type DRUG

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of delayed response: Continuation of antibiotic therapy for up to 5 days

Long arm

Antibiotic therapy for 5 to 7 days depending on response

Group Type ACTIVE_COMPARATOR

Quick response: Amoxicillin for 5 days

Intervention Type DRUG

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of rapid response\*: Continuation of antibiotherapy for up to 5 days

\*A rapid response is determined by a favorable clinical evolution (MASCOT 2002 study)

Delayed response: Amoxicillin for 7 days

Intervention Type DRUG

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of delayed response: Continuation of antibiotic therapy for up to 7 days

Interventions

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Quick response: Amoxicillin for 3 days

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of rapid response\*: Immediate stop of antibiotherapy (after 9 complete doses)

\*A rapid response is determined by a favorable clinical evolution (MASCOT 2002 study)

Intervention Type DRUG

Delayed response: Amoxicillin for 5 days

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of delayed response: Continuation of antibiotic therapy for up to 5 days

Intervention Type DRUG

Quick response: Amoxicillin for 5 days

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of rapid response\*: Continuation of antibiotherapy for up to 5 days

\*A rapid response is determined by a favorable clinical evolution (MASCOT 2002 study)

Intervention Type DRUG

Delayed response: Amoxicillin for 7 days

Once the diagnosis of community-acquired alveolar pneumonia has been made, the investigator taking charge of the child writes a prescription for amoxicillin at a dosage of 80-100 mg/kg/day in 3 oral doses (morning, noon and evening), for a period of 4 days, before delivery of treatment to the family. The investigator will carry out a clinical re-evaluation on day 3 (D3), during which he will decide on the final duration of treatment.

In case of delayed response: Continuation of antibiotic therapy for up to 7 days

Intervention Type DRUG

Other Intervention Names

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Quick response (3 days) Delayed response (5 days) Quick response (5 days) Delayed response (7 days)

Eligibility Criteria

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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
Minimum Eligible Age

3 Months

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Direction Générale de l'Offre de Soins

OTHER_GOV

Sponsor Role collaborator

University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarah DUTRON, MD

Role: STUDY_DIRECTOR

University Hospital, Montpellier

Locations

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CHU de Montpellier

Montpellier, , France

Site Status

Countries

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France

Central Contacts

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Sarah DUTRON, MD

Role: CONTACT

+334.67.33.66.34

Carine JAILLET, CRA

Role: CONTACT

Facility Contacts

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Sarah DUTRON, MD

Role: primary

References

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Haider BA, Saeed MA, Bhutta ZA. Short-course versus long-course antibiotic therapy for non-severe community-acquired pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005976. doi: 10.1002/14651858.CD005976.pub2.

Reference Type BACKGROUND
PMID: 18425930 (View on PubMed)

Pakistan Multicentre Amoxycillin Short Course Therapy (MASCOT) pneumonia study group. Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. Lancet. 2002 Sep 14;360(9336):835-41. doi: 10.1016/S0140-6736(02)09994-4.

Reference Type BACKGROUND
PMID: 12243918 (View on PubMed)

Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Phiri M, Schmicker R, Hwang J, Ndamala CB, Phiri A, Lufesi N, May S. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. N Engl J Med. 2020 Jul 2;383(1):13-23. doi: 10.1056/NEJMoa1912400.

Reference Type BACKGROUND
PMID: 32609979 (View on PubMed)

Chang AB, Grimwood K. Antibiotics for Childhood Pneumonia - Do We Really Know How Long to Treat? N Engl J Med. 2020 Jul 2;383(1):77-79. doi: 10.1056/NEJMe2016328. No abstract available.

Reference Type BACKGROUND
PMID: 32609987 (View on PubMed)

Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: a double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J. 2014 Feb;33(2):136-42. doi: 10.1097/INF.0000000000000023.

Reference Type BACKGROUND
PMID: 23989106 (View on PubMed)

Cohen R, Angoulvant F, Biscardi S, Madhi F, Dubos F, Gillet Y. Antibiotic treatment of lower respiratory tract infections. Arch Pediatr. 2017 Dec;24(12S):S17-S21. doi: 10.1016/S0929-693X(17)30513-4.

Reference Type BACKGROUND
PMID: 29290229 (View on PubMed)

Gauzit R, Castan B, Bonnet E, Bru JP, Cohen R, Diamantis S, Faye A, Hitoto H, Issa N, Lebeaux D, Lesprit P, Maulin L, Poitrenaud D, Raymond J, Strady C, Varon E, Verdon R, Vuotto F, Welker Y, Stahl JP. Anti-infectious treatment duration: The SPILF and GPIP French guidelines and recommendations. Infect Dis Now. 2021 Mar;51(2):114-139. doi: 10.1016/j.idnow.2020.12.001. Epub 2020 Dec 31. No abstract available.

Reference Type BACKGROUND
PMID: 34158156 (View on PubMed)

Same RG, Amoah J, Hsu AJ, Hersh AL, Sklansky DJ, Cosgrove SE, Tamma PD. The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children. J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):267-273. doi: 10.1093/jpids/piaa055.

Reference Type BACKGROUND
PMID: 32525203 (View on PubMed)

Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. Mayo Clin Proc. 2011 Feb;86(2):156-67. doi: 10.4065/mcp.2010.0639.

Reference Type BACKGROUND
PMID: 21282489 (View on PubMed)

Angoulvant F, Cohen R, Doit C, Elbez A, Werner A, Bechet S, Bonacorsi S, Varon E, Levy C. Trends in antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharyngeal flora in children with acute otitis media in France before and after 13 valent pneumococcal conjugate vaccine introduction. BMC Infect Dis. 2015 Jun 21;15:236. doi: 10.1186/s12879-015-0978-9.

Reference Type BACKGROUND
PMID: 26093673 (View on PubMed)

Angoulvant F, Levy C, Grimprel E, Varon E, Lorrot M, Biscardi S, Minodier P, Dommergues MA, Hees L, Gillet Y, Craiu I, Zenkhri F, Dubos F, Guen CG, Launay E, Martinot A, Cohen R. Early impact of 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in children. Clin Infect Dis. 2014 Apr;58(7):918-24. doi: 10.1093/cid/ciu006. Epub 2014 Feb 13.

Reference Type BACKGROUND
PMID: 24532543 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://www.who.int/fr/news-room/fact-sheets/detail/pneumonia

WHO declared antimicrobial resistance one of the 10 biggest public health threats facing humanity

https://ansm.sante.fr/actualites/tous-engages-pour-un-meilleur-usage-des-antibiotiques

ANSM: All committed to better use of antibiotics (2021, November)

https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf

Review on antimicrobial resistance. Tackling drug-resistant infections globally: Final report and recommendations. (2016 May)

https://www.has-sante.fr/upload/docs/application/pdf/2014-02/conseils_prescription_antibiotiques_rapport_d_elaboration.pdf

General principles and advice for prescribing antibiotics as a first resort (2014, February)

Other Identifiers

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2024-512236-30-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

RECHMPL22_0399

Identifier Type: -

Identifier Source: org_study_id

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