A randomized controlled non-inferiority trial of placebo versus macrolide antibiotics for Mycoplasma pneumoniae infection in children with community-acquired pneumonia: trial protocol for the MYTHIC Study.

Humans Pneumonia, Mycoplasma / drug therapy Child Community-Acquired Infections / drug therapy Double-Blind Method Anti-Bacterial Agents / therapeutic use Child, Preschool Adolescent Mycoplasma pneumoniae / drug effects Treatment Outcome Equivalence Trials as Topic Azithromycin / therapeutic use Switzerland Multicenter Studies as Topic Time Factors Female Male Age Factors Macrolides / therapeutic use

Anti-inflammatory Antimicrobial Atypical pneumonia Azithromycin Carriage Colonization Diagnosis Resistance Respiratory tract infection Stewardship

Journal

Trials

ISSN: 1745-6215

Titre abrégé: Trials

Pays: England

ID NLM: 101263253

Informations de publication

Date de publication:
03 Oct 2024

Historique:

received: 22 05 2024

accepted: 27 08 2024

medline: 4 10 2024

pubmed: 4 10 2024

entrez: 3 10 2024

Statut: epublish

Résumé

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required.

DISCUSSION CONCLUSIONS

This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance.

TRIAL REGISTRATION BACKGROUND

ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024.

Identifiants

DOI: 10.1186/s13063-024-08438-6 PMID: 39363201

pubmed: 39363201

doi: 10.1186/s13063-024-08438-6

pii: 10.1186/s13063-024-08438-6

doi:

Substances chimiques

Anti-Bacterial Agents 0

Azithromycin 83905-01-5

Macrolides 0

Banques de données

ClinicalTrials.gov

['NCT06325293']

Types de publication

Journal Article Clinical Trial Protocol Comparative Study

Langues

eng

Sous-ensembles de citation

Pagination

655

Informations de copyright

Références

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