A Trial of Placebo Versus Macrolide for Mycoplasma Pneumoniae Childhood Pneumonia: MYTHIC Study (MYTHIC)

April 29, 2026 updated by: Christoph Berger

A Randomized Controlled Non-inferiority Trial of Placebo Versus Macrolide Antibiotics for Mycoplasma Pneumoniae Infection in Children With Community-acquired Pneumonia - the MYTHIC Study

The goal of this clinical trial is to compare a placebo (a look-alike substance that contains no active drug) with a commonly used antibiotic in children with Mycoplasma pneumoniae (a specific bacterium) induced community-acquired pneumonia. The main question it aims to answer is:

Is antibiotic treatment needed in Mycoplasma pneumoniae (a specific bacterium) induced pneumonia?

Participants will receive either a placebo or a antibiotic treatment and track their symptoms and vital signs until they are healthy.

Researchers will then compare the length of symptoms between the placebo and the antibiotic group.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Mycoplasma pneumoniae (M. pneumoniae) is the most frequently detected bacterial pathogen in community-acquired pneumonia (CAP) in hospitalized U.S. children. Prior to the COVID-19 pandemic, M. pneumoniae was responsible for 8-28% of childhood CAP and thus was substantially contributes to CAP being a leading cause of hospitalization in high-income settings and worldwide morbidity and mortality. After the corona virus disease (COVID)-19 pandemic, M. pneumoniae and its delayed re-emergence remains a thread to children's health. CAP accounts for more treatment days with antibiotics in children's hospitals in the U.S. than any other condition. Macrolides are the first-line treatment for M. pneumoniae infection. Still, there is a lack of evidence for macrolides' the effectiveness in the treatment of M. pneumoniae induced CAP; simultaneously there is an alarmingly increasing antimicrobial resistance among M. pneumoniae. Therefore, childhood CAP, and especially M. pneumoniae, is an important target for antimicrobial stewardship efforts and cost-effectiveness considerations.

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 for a M. pneumoniae infection with Immunoglobulin M (IgM) lateral flow assay. Patients will be randomized 1:1 to receive a 5-day-treatment of macrolides (azithromycin) or placebo.

Study Type

Interventional

Enrollment (Estimated)

376

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
    • Canton Ticino
      • Bellinzona, Canton Ticino, Switzerland, 6500
        • Not yet recruiting
        • Institute of Pediatrics of Southern Switzerland, EOC, Bellinzona, Switzerland
        • Contact:
        • Principal Investigator:
          • Lisa Kottanattu, Dr. med.
    • Canton of Aargau
      • Aarau, Canton of Aargau, Switzerland, 5001
        • Active, not recruiting
        • Children's Hospital Aarau, Switzerland
    • Canton of Basel-City
      • Basel, Canton of Basel-City, Switzerland, 4056
        • Recruiting
        • University of Basel Children's Hospital, Switzerland
        • Contact:
        • Principal Investigator:
          • Julia A Bielicki, PD Dr. Dr. med.
        • Sub-Investigator:
          • Ulrich Heiniger, Prof. Dr. med.
    • Canton of Bern
      • Bern, Canton of Bern, Switzerland, 3010
        • Recruiting
        • University Children's Hospital Bern, Switzerland
        • Contact:
        • Principal Investigator:
          • Philipp Agyeman, PD Dr. med.
        • Sub-Investigator:
          • Kristina Keitel, PD Dr. Dr. med.
    • Canton of Fribourg
      • Fribourg, Canton of Fribourg, Switzerland, 1708
        • Not yet recruiting
        • Department of Pediatrics, Fribourg Hospital, Switzerland
        • Contact:
        • Principal Investigator:
          • Petra Zimmermann, PD Dr. Dr. med.
    • Canton of Geneva
      • Geneva, Canton of Geneva, Switzerland, 1205
        • Not yet recruiting
        • Children's Hospital of Geneva, University Hospitals of Geneva, Switzerland
        • Contact:
        • Principal Investigator:
          • Noémie Wagner, Dr. med.
    • Canton of Lucerne
      • Lucerne, Canton of Lucerne, Switzerland, 6000
        • Recruiting
        • Children's Hospital of Central Switzerland, Switzerland
        • Contact:
        • Principal Investigator:
          • Alex Donas, Dr. med.
    • Canton of St. Gallen
      • Sankt Gallen, Canton of St. Gallen, Switzerland, 9006
        • Recruiting
        • Children's Hospital of Eastern Switzerland St. Gallen
        • Contact:
        • Principal Investigator:
          • Anita Niederer-Loher, Dr. med.
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Switzerland, 1011
        • Not yet recruiting
        • Department of Pediatrics, Department Mother-Woman-Child, Lausanne University Hospital, Switzerland
        • Contact:
        • Principal Investigator:
          • Ludivine Coulon, Dr. med.
    • Canton of Zurich
      • Winterthur, Canton of Zurich, Switzerland, 8401
        • Recruiting
        • Department of Pediatrics, Cantonal Hospital Winterthur, Switzerland
        • Contact:
        • Principal Investigator:
          • Andreas Jung, Dr. med.
      • Zurich, Canton of Zurich, Switzerland, 8032
        • Recruiting
        • University Children's Hospital Zurich, Switzerland
        • Contact:
        • Principal Investigator:
          • Michelle Seiler, PD Dr. med
      • Zurich, Canton of Zurich, Switzerland, 8063
        • Not yet recruiting
        • Department of Pediatrics, Triemli Hospital Zurich, Switzerland
        • Contact:
        • Principal Investigator:
          • Maren Tomaske, Prof. Dr. med.
    • Kanton Graubünden
      • Chur, Kanton Graubünden, Switzerland, 7000
        • Recruiting
        • Department of Pediatrics, Cantonal Hospital Graubuenden, Switzerland
        • Contact:
        • Principal Investigator:
          • Beate Deubzer, Dr. med.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion criteria for screening phase:

  • Children aged 3-17 years (from 3rd up to 18th birthday) presenting to the emergency department (ED) who will be managed ambulatory or will be admitted to general ward.

  • Clinical diagnosis of CAP:

    1. Diagnosis defined as the treating physician's documented diagnosis of CAP; AND
    2. Fever ≥38.0°C (measured by any method [i.e., ear, axillary, rectal, or forehead site] in the ED or via parent report observed in the last 24h); AND
    3. Tachypnea (defined as respiratory rate (RR) above age-specific reference value) during the assessment in ED (triage or clinical examination).
  • Written screening consent for participation in screening phase signed by parents/legal guardians and the patient if ≥14 years of age.

Additional inclusion criteria for intervention phase:

  • Positive Mp screening test result with the Mp IgM lateral flow assay (LFA) (grade 2 or 3).
  • Written informed consent for participation in intervention phase signed by parents or legal guardians and the patient if ≥14 years of age.

Exclusion criteria:

Exclusion criteria for screening phase:

• None.

Exclusion criteria for intervention phase:

  • Contraindication to azithromycin: Documented allergy to azithromycin; cardiovascular disease, including bradycardia, arrhythmias, and/or QT-interval prolongation*; myasthenia gravis.

    *Co-medication with arrhythmogenic or QT-interval-prolonging drug (www.qtdrugs.org) is no exclusion criteria but will be discussed with the local investigators and/or trial management team (TMT).

  • Underlying comorbidities: Cystic fibrosis or other chronic lung disorders (excluding asthma), primary or secondary immunodeficiency, sickle-cell anemia, or severe cerebral palsy.
  • History of recurrent pneumonia (two or more episodes) or severe pneumonia (ICU admission or complications of CAP such as lung abscess, effusion, and empyema) in lifetime.
  • Antibiotic treatment against Mp within the previous 7 days, including macrolides, tetracyclines, or fluoroquinolones.
  • Referral to ICU directly from the ED.
  • Inability to take oral medication.
  • Parents are unlikely to reliably complete follow up (FUP) visits and questionnaires (e.g., due to language barriers or living far from the study site).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IMP arm

Azithromycin Pfizer® powder for oral suspension:

1 daily dose for 5 days, 10mg/kg/day on day 1 and 5mg/kg/day on days 2-5
Drug: Azithromycin Pfizer®
Azithromycin Pfizer® powder for oral suspension will be used in the active comparator arm: 1 daily dose for 5 days, 10mg/kg/day on day 1 and 5mg/kg/day on days 2-5
Placebo Comparator: Placebo arm
5 days of placebo
Drug: Placebo
Control comparator arm: 5 days of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Co-primary outcome: days to normalization of all vital signs
Time Frame: From enrollment until normalization of all vital signs for at least 24h assessed up to 28 days.
Time (days) to normalization of all vital signs for at least 24h (efficacy), defined as temperature <38.0°C, respiratory rate and heart rate within age-specific reference ranges, and peripheral oxygen saturation (SpO2) on room air ≥93% assessed up to 28 days.
From enrollment until normalization of all vital signs for at least 24h assessed up to 28 days.
Co-primary outcome: community-acquired pneumonia(CAP)-related change in patient care status
Time Frame: From enrollment assessed up to 28 days.
CAP-related change in patient care status within 28 days (safety), such as (re-)admission or ICU transfer assessed up to 28 days.
From enrollment assessed up to 28 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall clinical outcome
Time Frame: From enrollment until end of treatment at 5 days.
Overall clinical outcome based on benefits and harms (DOOR/RADAR approach) according to documentation of clinical response (normalization of all VS) and solicited adverse events (AEs) 1x/24h at the end of treatment (day 5) and each FUP visit.
From enrollment until end of treatment at 5 days.
Time (days) to normalization of CAP-related symptoms
Time Frame: From enrollment until normalization of CAP-related symptoms assessed up to 28 days.
Time (days) to normalization of CAP-related symptoms assessed up to 28 days.
From enrollment until normalization of CAP-related symptoms assessed up to 28 days.
Quality of Life (QoL) Assessment assessing impact of the child's pneumonia on the family's social and health-related well-being
Time Frame: From enrollment assessed up to 28 days.
QoL assessment of the patient's family with the pediatric quality of life inventory TM (PedsQLTM) family impact module and generic core scales questionnaire until day 28.
From enrollment assessed up to 28 days.
Time (days) to return to daily routine
Time Frame: From enrollment assessed up to 28 days.
Time (days) to return to daily routine, defined as return to childcare/school/work of patients and their families.
From enrollment assessed up to 28 days.
Incidence of Mp-associated extrapulmonary manifestations development in patients assessed by clinical examination and/or parent report
Time Frame: From enrollment assessed up to 28 days.
Development of Mp-associated extrapulmonary manifestations within 28 days after randomization based on clinical examination and/or parent report.
From enrollment assessed up to 28 days.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of hospital stay (LOS)
Time Frame: From enrollment assessed up to 28 days.
LOS (days) in hospitalized patients after index hospitalization.
From enrollment assessed up to 28 days.
Number of unscheduled medical visits
Time Frame: From enrollment assessed up to 28 days.
Number of unscheduled medical visits (apart from the study) until day 28.
From enrollment assessed up to 28 days.
Proportion of patients (re-)treated with antibiotics for any reason
Time Frame: From enrollment assessed up to 28 days.
Proportion of patients (re-)treated with antibiotics for any reason until 28 days and total antibiotic exposure in days up to 28 days.
From enrollment assessed up to 28 days.
Side effects/AEs/serious AE (SAE)s of investigational medicinal product (IMP)
Time Frame: From enrollment until end of treatment at 5 days.
Side effects/AEs/SAEs of IMP.
From enrollment until end of treatment at 5 days.
Microbiological indicators
Time Frame: From enrollment assessed up to 28 days.
Microbiological indicators (proportion of patients who cleared Mp in the upper respiratory tract (URT) within 28 days, proportion of patients in which Mp became resistant to macrolides within 28 days, proportion of patients with change in co-detecting pathogens in the URT at day 3 and 28) and inflammatory indicators (biomarker and cytokine profiling at day 3 and 28).
From enrollment assessed up to 28 days.
Other additional outcome independent of study intervention: Degree of usefulness of informational video about the study
Time Frame: From enrollment assessed up to 28 days.
Degree of usefulness of informational video about the study on a five-point Likert scale. Low scores indicate a low degree of usefulness and high scores indicate a high degree of usefulness.
From enrollment assessed up to 28 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christoph Berger

Collaborators

Swiss National Science Foundation
Swiss Clinical Trial Organisation
SwissPedNet

Investigators

  • Study Chair: Christoph Berger, Prof. Dr. med., University Children's hospital, Zürich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2025

Primary Completion (Estimated)

November 30, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

March 15, 2024

First Posted (Actual)

March 22, 2024

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-01295
  • 207286 (Other Grant/Funding Number: Swiss National Science Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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