Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06325293
Other study ID # 2023-01295
Secondary ID 207286
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date July 1, 2024
Est. completion date June 30, 2028

Study information

Verified date June 2024
Source University Children's Hospital, Zurich
Contact Patrick M Meyer Sauteur, PD Dr. Dr. med.
Phone 0041 44 266 78 96
Email patrick.meyersauteur@kispi.uzh.ch
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 376
Est. completion date June 30, 2028
Est. primary completion date June 30, 2028
Accepts healthy volunteers No
Gender All
Age group 3 Years to 17 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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
Control comparator arm: 5 days of placebo

Locations

Country Name City State
Switzerland Children's Hospital Aarau, Switzerland Aarau Aargau
Switzerland University of Basel Children's Hospital, Switzerland Basel Basel-Stadt
Switzerland Institute of Pediatrics of Southern Switzerland, EOC, Bellinzona, Switzerland Bellinzona Ticino
Switzerland University Children's Hospital Bern, Switzerland Bern
Switzerland Department of Pediatrics, Cantonal Hospital Graubuenden, Switzerland Chur Graubünden
Switzerland Department of Pediatrics, Fribourg Hospital, Switzerland Fribourg
Switzerland Children's Hospital of Geneva, University Hospitals of Geneva, Switzerland Geneva
Switzerland Department of Pediatrics, Department Mother-Woman-Child, Lausanne University Hospital, Switzerland Lausanne Vaud
Switzerland Children's Hospital of Central Switzerland, Switzerland Luzern
Switzerland Children's Hospital of Eastern Switzerland St. Gallen St. Gallen Saint Gallen
Switzerland Department of Pediatrics, Cantonal Hospital Winterthur, Switzerland Winterthur Zurich
Switzerland Department of Pediatrics, Triemli Hospital Zurich, Switzerland Zurich
Switzerland University Children's Hospital Zurich, Switzerland Zurich

Sponsors (1)

Lead Sponsor Collaborator
Christoph Berger

Country where clinical trial is conducted

Switzerland, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Length of hospital stay (LOS) LOS (days) in hospitalized patients after index hospitalization. From enrollment assessed up to 28 days.
Other Number of unscheduled medical visits Number of unscheduled medical visits (apart from the study) until day 28. From enrollment assessed up to 28 days.
Other Proportion of patients (re-)treated with antibiotics for any reason 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.
Other Side effects/AEs/serious AE (SAE)s of investigational medicinal product (IMP) Side effects/AEs/SAEs of IMP. From enrollment until end of treatment at 5 days.
Other Microbiological indicators 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 Other additional outcome independent of study intervention: Degree of usefulness of informational video about the study 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.
Primary 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.
Primary 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 Overall clinical outcome 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.
Secondary Time (days) to normalization of CAP-related symptoms 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.
Secondary Quality of Life (QoL) Assessment assessing impact of the child's pneumonia on the family's social and health-related well-being 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.
Secondary Time (days) to return to daily routine 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.
Secondary Incidence of Mp-associated extrapulmonary manifestations development in patients assessed by clinical examination and/or parent report 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.
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06348095 - Effect of Probiotics on Mycoplasma Pneumoniae Pneumonia N/A
Recruiting NCT02618057 - Effects of Oral Steroid in Mycoplasma Pneumoniae Pneumonia Phase 4
Not yet recruiting NCT04296383 - Xiyanping Injection Combined With Azithromycin VS Azithromycin for Children With pneumoniaProtozoal Pneumonia N/A
Completed NCT02303587 - Methylprednisolone for Children With Severe Mycoplasma Pneumoniae Pneumonia (MCMP) N/A