- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04043325
Diagnosis of Mycoplasma Pneumoniae Infection With Detection of Specific Antibody-secreting Cells in Community-acquired Pneumonia (CAP) Patients of the Randomised Placebo-controlled Multi-centre Effectiveness Trial of Adjunct Betamethasone Therapy (myKIDS-STEP)
Diagnosis of Mycoplasma Pneumoniae Infection With Detection of Specific Antibody-secreting Cells in Community-acquired Pneumonia (CAP) Patients of the Randomised Placebo-controlled Multi-centre Effectiveness Trial of Adjunct Betamethasone Therapy (myKIDS-STEP)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Community-acquired pneumonia (CAP) is a common serious infection and a leading cause of hospitalisation in children. Knowledge about the underlying pathogen is a major unmet clinical need, particularly in CAP caused by Mycoplasma pneumoniae (Mp). Timely and reliable identification is critical for initiating effective and tailored antimicrobial treatment. However, determining the causative pathogen of childhood CAP is complicated by the low yield of blood cultures and difficulty obtaining specimens from the lower respiratory tract of children. Therefore, clinicians attempt to detect potential pathogens in upper respiratory tract (URT) specimens, knowing that children carry viruses and bacteria in their URT that may or may not be causative for the current pneumonia episode. Consequently, the interpretation of diagnostic tests performed with URT specimens is limited and may lead to unnecessary antimicrobial prescriptions.
The hurdle in differentiating infection from carriage was documented recently for Mp, a frequently reported pathogen underlying CAP in children worldwide (up to 20-40% during epidemics). Current diagnostic tests, including polymerase chain reaction (PCR) of URT specimens or serology, do not reliable differentiate between Mp infection and carriage. Mp is found in the URT in up to 56% of healthy children. These findings challenge recent epidemiological data indicating Mp as the most common bacterial cause of CAP, in up to 23% of hospitalized U.S. children aged 10-17 years. A ≥4-fold increase in IgG antibody levels is still considered the "gold standard" for diagnosing M. pneumoniae infection, but has low sensitivity when e.g. compared with IgM seroconversion and/or a 2-fold IgM increase. In fact, such a definition is also not helpful in acute clinical management, as it requires acute and convalescent sera.
Circulating antigen-specific B cell responses have been investigated in vaccine studies and demonstrated to be more rapid and shorter lived than antibody responses. After exposure, antigen-specific B cells proliferate and differentiate into antibody-secreting cells (ASCs) and memory B cells. ASCs transiently circulate in the peripheral blood in the first days after an antigen encounter. In a recent observational pilot study of children with CAP and healthy controls, we showed that the detection of Mp-specific immunoglobulin (Ig) M ASCs by enzyme-linked immunospot (ELISpot) assay re-classified 15% of PCR-positive and 12% of IgM-seropositive study participants (https://doi.org/10.1164/rccm.201904-0860LE). Thus, the measurement of specific IgM ASCs by ELISpot assay is an innovative, minimally invasive, and rapid test method that optimises diagnosis of Mp CAP in children.
In view of these promising first results, the aim of this study is to establish the diagnosis of Mp infection by the measurement of Mp-specific ASCs by ELISpot in CAP patients enroled in the randomised placebo-controlled multi-centre effectiveness trial of adjunct betamethasone therapy (KIDS-STEP study, Protocol ID: NCT03474991).
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Patrick M. Meyer Sauteur, MD PhD
- Phone Number: +41442667896
- Email: patrick.meyer@kispi.uzh.ch
Study Locations
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Zürich, Switzerland, 8032
- Recruiting
- University Children's Hospital Zurich
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Contact:
- Patrick M. Meyer Sauteur, MD PhD
- Phone Number: +41442667896
- Email: patrick.meyer@kispi.uzh.ch
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Contact:
- Christoph Berger, MD
- Phone Number: +41442667840
- Email: christoph.berger@kispi.uzh.ch
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- At least 12 months of age and younger than 10 years of age
- Body weight between 7 kg and 35 kg
- Admission to hospital (i.e. assignment of an inpatient case number)
- Clinical diagnosis of CAP (according to predefined criteria)
- Parent and/or child (as age-appropriate) willing to accept all possible randomised allocations and to be contacted by telephone weekly up to and including at 4 weeks after randomisation
- Informed consent form for trial participation signed by parent
Exclusion Criteria:
- Presence of local chest complications
- Chronic underlying disease associated with an increased risk of very severe CAP or CAP of unusual aetiology
- Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection affecting the medium airways, i.e. not pneumonia)
- Inability to tolerate oral medication
- Documented allergy or any other known contraindication to any trial medication
- Subacute or chronic conditions requiring higher betamethasone equivalent or known primary or secondary adrenal insufficiency
- Known diabetes mellitus (type 1)
- Hospitalisation within the last two weeks preceding current admission
- Exposure to systemic corticosteroids with completion of treatment <2 weeks from enrolment (courses of up to 7 days) or <4 weeks from enrolment (courses of >7 days)
- Transfer for any reason to a non-participating hospital directly from the paediatric emergency department
- Parent are unlikely to be able to reliably participate in telephone follow-up because of significant language barriers
- Participation in another study with investigational drug within the 30 days preceding and during the present study,
- Previous enrolment into the current study,
- Enrolment of the investigator, his/her family members, and other dependent persons.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Detection of Mp-specific IgM ASCs by ELISpot assay
Time Frame: Day 1 (at enrolment)
|
Diagnosis of Mp infection in CAP patients of the KIDS-STEP study with the detection of Mp-specific IgM ASCs by ELISpot assay at enrolment (day 1).
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Day 1 (at enrolment)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
No detection of Mp-specific IgM ASCs by ELISpot assay
Time Frame: Day 28
|
Longitudinal assessment of levels of Mp-specific IgM ASCs by ELISpot assay.
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Day 28
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Detection of Mp-specific DNA by PCR
Time Frame: Day 28
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Longitudinal assessment of levels of Mp-specific DNA by PCR.
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Day 28
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Detection of Mp-specific IgM by ELISA
Time Frame: Day 28
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Longitudinal assessment of levels of Mp-specific IgM by ELISA.
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Day 28
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Detection of specific IgM ASCs against other pathogens by ELISpot assay
Time Frame: Day 1
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Diagnosis of infection with other respiratory pathogens than Mp in CAP patients of the KIDS-STEP study with the detection of specific IgM ASCs by ELISpot assay at enrolment (day 1).
|
Day 1
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Pneumonia, Bacterial
- Mycoplasmatales Infections
- Mycoplasma Infections
- Pneumonia
- Pneumonia, Mycoplasma
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
Other Study ID Numbers
- 2019-00425
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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