Stopping Pneumonia Antibiotherapy Regimen Early

NCT06291012 | Not Yet Recruiting Phase 4

• 2 other identifiers: RECHMPL22_03992024-512236-30-00
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 1

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.

Conditions

Community-acquired Pneumonia; Child, Only

Keywords

Antibiotics management; Amoxicillin

Outcome Measures

Primary Outcomes (1)

• Therapeutic failure rate D7

  Day 0 (D0) is defined as the 1st day of taking amoxicillin. The rate of therapeutic failure on day 7 (D7) defined by: * A change in antibiotherapy necessary before D7 due to a lack of satisfactory clinical response or clinical deterioration of the pneumonia. * A decision to resume or continue antibiotic therapy after D7 in connection with the pneumonia. * Hospitalization or death due to clinical deterioration related to community-acquired pneumonia. This definition is based on that already used in a clinical trial carried out in Israel (6. 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. Pediatr Infect Dis J. 2014 Feb;33(2):136-42).

  Day 7

Secondary Outcomes (4)

• Therapeutic failure rate on D30

  Day 30

• Adverse effects

  Day 0, Day 3, Day 7 and Day 30

• Compliance

  Day 7, or Day 30 in case of therapeutic failure

• Duration of antibiotic therapy

  Day 7 and Day 30

Study Arms (2)

Short arm

EXPERIMENTAL

Antibiotic therapy for 3 to 5 days depending on response

Drug: Quick response: Amoxicillin for 3 days; Drug: Delayed response: Amoxicillin for 5 days

Long arm

ACTIVE COMPARATOR

Antibiotic therapy for 5 to 7 days depending on response

Drug: Quick response: Amoxicillin for 5 days; Drug: Delayed response: Amoxicillin for 7 days

Interventions

Quick response: Amoxicillin for 3 days 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)

Also known as: Quick response (3 days)

Short arm

Delayed response: Amoxicillin for 5 days 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

Also known as: Delayed response (5 days)

Short arm

Quick response: Amoxicillin for 5 days 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)

Also known as: Quick response (5 days)

Long arm

Delayed response: Amoxicillin for 7 days 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

Also known as: Delayed response (7 days)

Long arm

Eligibility Criteria

• Age: 3 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Absence of hospitalization criteria

You may not qualify if:

• 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
• Allergy or contraindication to penicillin
• History of more than 2 bacterial pneumonias per year
• Associated infection requiring more than 3 days of antibiotics
• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Direction Générale de l'Offre de Soins: collaborator

Study Sites (1)

CHU de Montpellier

Montpellier, 34295, France

Location

Related Publications (11)

• 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.

  PMID: 18425930 BACKGROUND

• 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.

  PMID: 12243918 BACKGROUND

• 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.

  PMID: 32609979 BACKGROUND

• 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.

  PMID: 32609987 BACKGROUND

• 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.

  PMID: 23989106 BACKGROUND

• 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.

  PMID: 29290229 BACKGROUND

• 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.

  PMID: 34158156 BACKGROUND

• 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.

  PMID: 32525203 BACKGROUND

• 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.

  PMID: 21282489 BACKGROUND

• 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.

  PMID: 26093673 BACKGROUND

• 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.

  PMID: 24532543 BACKGROUND

Related Links

• WHO declared antimicrobial resistance one of the 10 biggest public health threats facing humanity
• ANSM: All committed to better use of antibiotics (2021, November)
• Review on antimicrobial resistance. Tackling drug-resistant infections globally: Final report and recommendations. (2016 May)
• General principles and advice for prescribing antibiotics as a first resort (2014, February)

MeSH Terms

Conditions

Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Sarah DUTRON, MD

  University Hospital, Montpellier

  STUDY DIRECTOR

Central Study Contacts

Sarah DUTRON, MD

CONTACT

+334.67.33.66.34; s-dutron@chu-montpellier.fr

Carine JAILLET, CRA

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The randomization will be carried out by minimization with stratification on the investigating center and age (\< 1 year and ≥ 1 year)

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)