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

NCT06325293 | Recruiting DMC

• 2 other identifiers: 2023-01295207286
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Community Acquired Pneumonia in Children; Mycoplasma Pneumoniae; Mycoplasma Pneumoniae Pneumonia

Keywords

Mycoplasma pneumoniae; community-acquired pneumonia; randomized controlled trial; Investigator Initiated Clinical Trial (IICT); Paediatric pneumonia; children; placebo; macrolides

Outcome Measures

Primary Outcomes (2)

• Co-primary outcome: days to normalization of all vital signs

  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

  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 Outcomes (5)

• Overall clinical outcome

  From enrollment until end of treatment at 5 days.

• Time (days) to normalization of CAP-related symptoms

  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

  From enrollment assessed up to 28 days.

• Time (days) to return to daily routine

  From enrollment assessed up to 28 days.

• Incidence of Mp-associated extrapulmonary manifestations development in patients assessed by clinical examination and/or parent report

  From enrollment assessed up to 28 days.

Other Outcomes (6)

• Length of hospital stay (LOS)

  From enrollment assessed up to 28 days.

• Number of unscheduled medical visits

  From enrollment assessed up to 28 days.

• Proportion of patients (re-)treated with antibiotics for any reason

  From enrollment assessed up to 28 days.

Study Arms (2)

IMP arm

ACTIVE COMPARATOR

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®

Placebo arm

PLACEBO COMPARATOR

5 days of placebo

Drug: Placebo

Interventions

Azithromycin Pfizer® 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

IMP arm

Placebo DRUG

Control comparator arm: 5 days of placebo

Placebo arm

Eligibility Criteria

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

You may qualify if:

• 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:
• Diagnosis defined as the treating physician's documented diagnosis of CAP; AND
• 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
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Swiss National Science Foundation: collaborator
• Christoph Berger: lead
• Swiss Clinical Trial Organisation: collaborator
• SwissPedNet: collaborator

Study Sites (13)

Children's Hospital Aarau, Switzerland

Aarau, Canton of Aargau, 5001, Switzerland

ACTIVE NOT RECRUITING

University of Basel Children's Hospital, Switzerland

Basel, Canton of Basel-City, 4056, Switzerland

RECRUITING

University Children's Hospital Bern, Switzerland

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

Department of Pediatrics, Fribourg Hospital, Switzerland

Fribourg, Canton of Fribourg, 1708, Switzerland

NOT YET RECRUITING

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

Geneva, Canton of Geneva, 1205, Switzerland

NOT YET RECRUITING

Children's Hospital of Central Switzerland, Switzerland

Lucerne, Canton of Lucerne, 6000, Switzerland

RECRUITING

Children's Hospital of Eastern Switzerland St. Gallen

Sankt Gallen, Canton of St. Gallen, 9006, Switzerland

RECRUITING

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

Lausanne, Canton of Vaud, 1011, Switzerland

NOT YET RECRUITING

Department of Pediatrics, Cantonal Hospital Winterthur, Switzerland

Winterthur, Canton of Zurich, 8401, Switzerland

RECRUITING

University Children's Hospital Zurich, Switzerland

Zurich, Canton of Zurich, 8032, Switzerland

RECRUITING

Department of Pediatrics, Triemli Hospital Zurich, Switzerland

Zurich, Canton of Zurich, 8063, Switzerland

NOT YET RECRUITING

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

Bellinzona, Canton Ticino, 6500, Switzerland

NOT YET RECRUITING

Department of Pediatrics, Cantonal Hospital Graubuenden, Switzerland

Chur, Kanton Graubünden, 7000, Switzerland

RECRUITING

Related Publications (9)

• 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.

  PMID: 31665253 BACKGROUND

• 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.

  PMID: 32034406 BACKGROUND

• 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.

  PMID: 31251669 BACKGROUND

• 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.

  PMID: 38008103 BACKGROUND

• 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.

  PMID: 29788037 BACKGROUND

• 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.

  PMID: 29084336 BACKGROUND

• 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.

  PMID: 24864174 BACKGROUND

• 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.

  PMID: 25566754 BACKGROUND

• 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.

  PMID: 39363201 DERIVED

MeSH Terms

Conditions

Pneumonia, Mycoplasma; Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Mycoplasma Infections; Mycoplasmatales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections

Study Officials

• Christoph Berger, Prof. Dr. med.

  University Children's Hospital, Zurich

  STUDY CHAIR

Central Study Contacts

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

CONTACT

0041 44 266 78 96; patrick.meyersauteur@kispi.uzh.ch

Margarete Von Wantoch, Dr. rer. nat.

CONTACT

0041 044 266 38 32; Margarete.VonWantoch@kispi.uzh.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: This is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial.

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 22, 2024
• Study Start: January 28, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (13)