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

NCT ID: NCT06325293

Last Updated: 2025-03-30

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

RECRUITING

Clinical Phase

NA

Total Enrollment

376 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-28

Study Completion Date

2028-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Community Acquired Pneumonia in Children Mycoplasma Pneumoniae Mycoplasma Pneumoniae Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Azithromycin Pfizer®

Intervention Type DRUG

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 arm

5 days of placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Control comparator arm: 5 days of placebo

Interventions

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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

Intervention Type DRUG

Placebo

Control comparator arm: 5 days of placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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

• None.


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

* 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).
Minimum Eligible Age

3 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SNF Swiss National Foundation

UNKNOWN

Sponsor Role collaborator

Swiss Clinical Trial Organisation

UNKNOWN

Sponsor Role collaborator

SwissPedNet

UNKNOWN

Sponsor Role collaborator

Christoph Berger

OTHER

Sponsor Role lead

Responsible Party

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Christoph Berger

Prof. Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Christoph Berger, Prof. Dr. med.

Role: STUDY_CHAIR

University Children's Hospital, Zurich

Locations

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Children's Hospital Aarau, Switzerland

Aarau, Canton of Aargau, Switzerland

Site Status ACTIVE_NOT_RECRUITING

University of Basel Children's Hospital, Switzerland

Basel, Canton of Basel-City, Switzerland

Site Status RECRUITING

University Children's Hospital Bern, Switzerland

Bern, Canton of Bern, Switzerland

Site Status RECRUITING

Department of Pediatrics, Fribourg Hospital, Switzerland

Fribourg, Canton of Fribourg, Switzerland

Site Status NOT_YET_RECRUITING

Children's Hospital of Geneva, University Hospitals of Geneva, Switzerland

Geneva, Canton of Geneva, Switzerland

Site Status NOT_YET_RECRUITING

Children's Hospital of Central Switzerland, Switzerland

Lucerne, Canton of Lucerne, Switzerland

Site Status RECRUITING

Children's Hospital of Eastern Switzerland St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status RECRUITING

Department of Pediatrics, Department Mother-Woman-Child, Lausanne University Hospital, Switzerland

Lausanne, Canton of Vaud, Switzerland

Site Status NOT_YET_RECRUITING

Department of Pediatrics, Cantonal Hospital Winterthur, Switzerland

Winterthur, Canton of Zurich, Switzerland

Site Status RECRUITING

University Children's Hospital Zurich, Switzerland

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Department of Pediatrics, Triemli Hospital Zurich, Switzerland

Zurich, Canton of Zurich, Switzerland

Site Status NOT_YET_RECRUITING

Institute of Pediatrics of Southern Switzerland, EOC, Bellinzona, Switzerland

Bellinzona, Canton Ticino, Switzerland

Site Status NOT_YET_RECRUITING

Department of Pediatrics, Cantonal Hospital Graubuenden, Switzerland

Chur, Kanton Graubünden, Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Patrick M Meyer Sauteur, PD Dr. Dr. med.

Role: CONTACT

0041 44 266 78 96

Margarete Von Wantoch, Dr. rer. nat.

Role: CONTACT

0041 044 266 38 32

Facility Contacts

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Julia A Bielicki, PD Dr. Dr. med.

Role: primary

0041 61 704 12 12

Philipp Agyeman, PD Dr. med.

Role: primary

0041 31 632 21 11

Petra Zimmermann, PD Dr. Dr. med.

Role: primary

0041 26 306 00 00

Noémie Wagner, Dr. med.

Role: primary

0041 22 372 40 00

Alex Donas, Dr. med.

Role: primary

0041 41 205 31 66

Anita Niederer-Loher, Dr. med.

Role: primary

0041 71 243 71 11

Ludivine Coulon, Dr. med.

Role: primary

0041 21 314 11 11

Andreas Jung, Dr. med.

Role: primary

0041 52 266 41 44

Michelle Seiler, PD Dr. med

Role: primary

0041 44 266 71 11

Maren Tomaske, Prof. Dr. med.

Role: primary

0041 44 416 11 11

Lisa Kottanattu, Dr. med.

Role: primary

0041 91 811 91 11

Beate Deubzer, Dr. med.

Role: primary

0041 81 256 61 11

References

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Meyer Sauteur PM, Krautter S, Ambroggio L, Seiler M, Paioni P, Relly C, Capaul R, Kellenberger C, Haas T, Gysin C, Bachmann LM, van Rossum AMC, Berger C. Improved Diagnostics Help to Identify Clinical Features and Biomarkers That Predict Mycoplasma pneumoniae Community-acquired Pneumonia in Children. Clin Infect Dis. 2020 Oct 23;71(7):1645-1654. doi: 10.1093/cid/ciz1059.

Reference Type BACKGROUND
PMID: 31665253 (View on PubMed)

Meyer Sauteur PM, Truck J, van Rossum AMC, Berger C. Circulating Antibody-Secreting Cell Response During Mycoplasma pneumoniae Childhood Pneumonia. J Infect Dis. 2020 Jun 16;222(1):136-147. doi: 10.1093/infdis/jiaa062.

Reference Type BACKGROUND
PMID: 32034406 (View on PubMed)

Meyer Sauteur PM, Seiler M, Truck J, Unger WWJ, Paioni P, Relly C, Staubli G, Haas T, Gysin C, M Bachmann L, van Rossum AMC, Berger C. Diagnosis of Mycoplasma pneumoniae Pneumonia with Measurement of Specific Antibody-Secreting Cells. Am J Respir Crit Care Med. 2019 Oct 15;200(8):1066-1069. doi: 10.1164/rccm.201904-0860LE. No abstract available.

Reference Type BACKGROUND
PMID: 31251669 (View on PubMed)

Meyer Sauteur PM, Beeton ML; European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycoplasma and Chlamydia Infections (ESGMAC), and the ESGMAC Mycoplasma pneumoniae Surveillance (MAPS) study group. Mycoplasma pneumoniae: delayed re-emergence after COVID-19 pandemic restrictions. Lancet Microbe. 2024 Feb;5(2):e100-e101. doi: 10.1016/S2666-5247(23)00344-0. Epub 2023 Nov 23. No abstract available.

Reference Type BACKGROUND
PMID: 38008103 (View on PubMed)

Kutty PK, Jain S, Taylor TH, Bramley AM, Diaz MH, Ampofo K, Arnold SR, Williams DJ, Edwards KM, McCullers JA, Pavia AT, Winchell JM, Schrag SJ, Hicks LA. Mycoplasma pneumoniae Among Children Hospitalized With Community-acquired Pneumonia. Clin Infect Dis. 2019 Jan 1;68(1):5-12. doi: 10.1093/cid/ciy419.

Reference Type BACKGROUND
PMID: 29788037 (View on PubMed)

Williams DJ, Edwards KM, Self WH, Zhu Y, Arnold SR, McCullers JA, Ampofo K, Pavia AT, Anderson EJ, Hicks LA, Bramley AM, Jain S, Grijalva CG. Effectiveness of beta-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia. JAMA Pediatr. 2017 Dec 1;171(12):1184-1191. doi: 10.1001/jamapediatrics.2017.3225.

Reference Type BACKGROUND
PMID: 29084336 (View on PubMed)

Biondi E, McCulloh R, Alverson B, Klein A, Dixon A, Ralston S. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014 Jun;133(6):1081-90. doi: 10.1542/peds.2013-3729.

Reference Type BACKGROUND
PMID: 24864174 (View on PubMed)

Gardiner SJ, Gavranich JB, Chang AB. Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children. Cochrane Database Syst Rev. 2015 Jan 8;1(1):CD004875. doi: 10.1002/14651858.CD004875.pub5.

Reference Type BACKGROUND
PMID: 25566754 (View on PubMed)

Meyer Sauteur PM, Seiler M, Tilen R, Osuna E, von Wantoch M, Sidorov S, Aebi C, Agyeman P, Barbey F, Bielicki JA, Coulon L, Deubzer B, Donas A, Heininger U, Keitel K, Kohler H, Kottanattu L, Lauener R, Niederer-Loher A, Posfay-Barbe KM, Tomaske M, Wagner N, Zimmermann P, Zucol F, von Felten S, Berger C. 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. Trials. 2024 Oct 3;25(1):655. doi: 10.1186/s13063-024-08438-6.

Reference Type DERIVED
PMID: 39363201 (View on PubMed)

Other Identifiers

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207286

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2023-01295

Identifier Type: -

Identifier Source: org_study_id

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