Next Generation SequencingNCT03953638
Application of Next Generation Sequencing Technique in Pediatric Bacterial Meningitis
An observational study of Next Generation Sequencing and Pediatric Bacterial Meningitis, run by Beijing Children's Hospital at 1 site in China.
Trial summary
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. Read more about this study
- Who is it for?
- Ages 28 days to 18 years
- Conditions the study is for
- Next Generation Sequencing, Pediatric Bacterial Meningitis
- What is being tested?
- Next Generation Sequencing
- How many people
- 500 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2018to 31 Jul 2020
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients that are highly suspected of bacterial meningitis.
Who may be able to join
- Patients highly suspected of bacterial meningitis
Who cannot join
- Non-bacterial infectious central nervous system (CNS) confirmed by viral meningitis, tuberculous meningitis cryptococcal meningitis and so on
- Autoimmune encephalitis cases
- Central nervous system affected by neoplastic disease
- Hemorrhagic cerebrospinal fluid
- Less than 1ml cerebrospinal fluid
- Refusal to enter the group
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Children's Hospital
Beijing, Beijing Municipality, 100045
Gang Liu, 008613370115008, liugang10@hotmail.com
About this study
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, cerebrospinal fluid (CSF) culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. The emergence of powerful next-generation sequencing (NGS) technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Previous reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.
Read the detailed description
Bacterial meningitis, also known as purulent meningitis, is caused by a variety of bacterial infections. Although the incidence in infants and children has decreased since the use of conjugated vaccines targeting Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitides (N. meningitides), bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The causative pathogens of bacterial meningitis depend on different age of the patient and predisposing factors.
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, CSF culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. Although non-culture methods including multiplex PCR and latex agglutination, etc. have been used in clinical microbiology, only one or several specific pathogens could be targeted by these kinds of technology, let alone rare pathogens.
In recent years, the emergence of powerful NGS technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Wilson et al presented a case of neuroleptospirosis, resulting in a dramatic clinical improvement with intravenous penicillin after identifying leptospira infection in the CSF by unbiased NGS technology. Unbiased NGS could facilitate identification of all the potential pathogens in a single assay theoretically. Herpes simplex virus1, herpes simplex virus 2 and human herpes virus type 3 were detected using NGS technology from four cases with clinically suspected viral meningoencephalitis respectively. And the results were further validated using polymerase chain reaction (PCR). Further, Yao et al detected Listeria monocytogenes in CSF from three patients with meningoencephalitis by NGS. These reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.
- Being tested
- Next Generation Sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Next Generation SequencingDiagnostic test
To provide rapid etiological diagnosis of patients by means of next-generation sequencing.
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of next-generation sequencing in the pathogen detection of Pediatric Bacterial Meningitis
We aim to collect samples cerebrospinal fluid from patients with Pediatric Bacterial Meningitis. Next-generation sequencing will be performed on the collected samples. Our analysis of the sequencing results will focus on the analysis and identification of pathogen genes and will compare the diagnostic performance of next-generation sequencing with conventional etiological diagnostic methods. We anticipate that next-generation sequencing in Pediatric Bacterial Meningitis will show a greater diagnostic value than the traditional methods (including culture, special pathogen antigen, PCR detection of nucleic acids, etc.).
Measured: 2 years
Secondary outcomes (1)
Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of traditional methods in the pathogen detection of infectious diseases
We aim to collect CSF samples from patients with pediatric bacterial meningitis. Traditional methods including culture, special pathogen serology, PCR detection of nucleic acids, etc, will be performed on the collected samples. Our analysis aims to study the diagnostic power of the traditional diagnostic methods in infectious diseases.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start1 Feb 2018
- Primary completion31 Jan 2020 (estimated)
- Study completion31 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Next Generation SequencingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Beijing Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Xingtai People's Hospital, Baoding Children's Hospital, Children's Hospital Affiliated to Shandong University, Liaocheng People's Hospital, Nanjing Children's Hospital, Shenzhen Baoan Maternal and Child Care Service Centre, Jiangxi Province Children's Hospital, Kunming Children's Hospital, First Affiliated Hospital of Xinjiang Medical University, Children's Hospital Affiliated to Suzhou University
- Responsible party
- Principal investigator, Gang Liu, Beijing Children's Hospital
- Investigators
- Gang Liu, Principal investigator, Beijing Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03953638
- Sponsor's protocol ID
- 20190514
- Status last verified
- May 2019
- First submitted
- 15 May 2019
- Last updated
- 16 May 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Next Generation Sequencing Technique in Pediatric Bacterial Meningitis
- ClinicalTrials.gov ID
- NCT03953638
- Acronym / sponsor ID
- 20190514
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Beijing Children's HospitalUniversity, hospital or other
- Collaborators
- Xingtai People's Hospital, Baoding Children's Hospital, Children's Hospital Affiliated to Shandong University, Liaocheng People's Hospital, Nanjing Children's Hospital, Shenzhen Baoan Maternal and Child Care Service Centre, Jiangxi Province Children's Hospital, Kunming Children's Hospital, First Affiliated Hospital of Xinjiang Medical University, Children's Hospital Affiliated to Suzhou University
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 31 Jan 2020 (estimated)
- Study completion
- 31 Jul 2020 (estimated)
- First posted
- 16 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, cerebrospinal fluid (CSF) culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. The emergence of powerful next-generation sequencing (NGS) technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Previous reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.
Detailed description
Bacterial meningitis, also known as purulent meningitis, is caused by a variety of bacterial infections. Although the incidence in infants and children has decreased since the use of conjugated vaccines targeting Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitides (N. meningitides), bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The causative pathogens of bacterial meningitis depend on different age of the patient and predisposing factors.
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, CSF culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. Although non-culture methods including multiplex PCR and latex agglutination, etc. have been used in clinical microbiology, only one or several specific pathogens could be targeted by these kinds of technology, let alone rare pathogens.
In recent years, the emergence of powerful NGS technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Wilson et al presented a case of neuroleptospirosis, resulting in a dramatic clinical improvement with intravenous penicillin after identifying leptospira infection in the CSF by unbiased NGS technology. Unbiased NGS could facilitate identification of all the potential pathogens in a single assay theoretically. Herpes simplex virus1, herpes simplex virus 2 and human herpes virus type 3 were detected using NGS technology from four cases with clinically suspected viral meningoencephalitis respectively. And the results were further validated using polymerase chain reaction (PCR). Further, Yao et al detected Listeria monocytogenes in CSF from three patients with meningoencephalitis by NGS. These reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 28 days to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients that are highly suspected of bacterial meningitis.
Key inclusion criteria (1 listed)
- Patients highly suspected of bacterial meningitis
Key exclusion criteria (6 listed)
- Non-bacterial infectious central nervous system (CNS) confirmed by viral meningitis, tuberculous meningitis cryptococcal meningitis and so on
- Autoimmune encephalitis cases
- Central nervous system affected by neoplastic disease
- Hemorrhagic cerebrospinal fluid
- Less than 1ml cerebrospinal fluid
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Next Generation SequencingTo provide rapid etiological diagnosis of patients by means of next-generation sequencing. | Diagnostic test | – |
Primary outcome
Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of next-generation sequencing in the pathogen detection of Pediatric Bacterial Meningitis
Time frame: 2 years
We aim to collect samples cerebrospinal fluid from patients with Pediatric Bacterial Meningitis. Next-generation sequencing will be performed on the collected samples. Our analysis of the sequencing results will focus on the analysis and identification of pathogen genes and will compare the diagnostic performance of next-generation sequencing with conventional etiological diagnostic methods. We anticipate that next-generation sequencing in Pediatric Bacterial Meningitis will show a greater diagnostic value than the traditional methods (including culture, special pathogen antigen, PCR detection of nucleic acids, etc.).
1 secondary outcome
Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of traditional methods in the pathogen detection of infectious diseases
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gang Liu principal investigator
Beijing Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Next Generation Sequencing and Pediatric Bacterial Meningitis, run by Beijing Children's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gang Liu (008613370115008, liugang10@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of next-generation sequencing in the pathogen detection of Pediatric Bacterial Meningitis (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2019.