SepsismiRNA-SepsisNCT02544490
Defining Circulating Micro-RNA Biomarkers for the Early Diagnosis and Prognosis of Sepsis
An observational study of Sepsis, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
The objectives are to: 1. derive and validate a panel of miRNAs that are consistently differentially expressed in the plasma of patients with and without sepsis 2. investigate the prognostic and predictive values of the panel of miRNAs to guide treatment 3. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sepsis
- How many people
- 450 participants
- Where
- 1 siteSingapore
- Study dates
- Sep 2013to Dec 2018
- 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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This research project will be a prospective observational cohort study of controls without infection and patients along the entire sepsis continuum the Emergency Department (ED). Admitted patients will be followed-up in the inpatient units including the intensive care unit (ICU) and general wards. Healthy controls and those with systemic inflammatory response syndrome (SIRS) but without evidence of infection will also be recruited to demonstrate differentiation of biomarkers for early diagnosis. The reference standards for infection and sepsis will be positive cultures (e.g. from blood, urine, endotracheal tube, sputum) and final discharge diagnoses.
Who may be able to join
- Adults 21 years and above
- Has condition unrelated to any infective cause
- Adults 21 years and above
- Clinical/radiological suspicion or confirmation of infection
Who cannot join
- Underlying chronic inflammatory condition (e.g. inflammatory bowel disease)
- Underlying autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus)
- Pre-existent immunological disorder
- Age below 21 years
- Prisoners
- Known pregnancy
Show all 12Show fewer
- Do-not-attempt resuscitation status
- Requirement for immediate surgery
- Active chemotherapy
- Hematological malignancy
- Treating physician deems aggressive care unsuitable
- Unable to provide informed consent or comply with study requirements
Trial locations and contacts
1 site in 1 country.
About this study
The objectives are to:
- derive and validate a panel of miRNAs that are consistently differentially expressed in the plasma of patients with and without sepsis
- investigate the prognostic and predictive values of the panel of miRNAs to guide treatment
- investigate the roles of these differentially-expressed circulating miRNAs in immune modulation during sepsis
The methodology involves sampling of blood from controls and subjects in the sepsis continuum at their earliest presentation in the emergency department longitudinally to hospitalization. The investigators will develop panels of miRNAs that are specific to early and late stages of sepsis, and correlate clinical, biochemical and microbiological outcomes with these miRNAs.
Read the detailed description
Prospective observational cohort of patients along the entire sepsis continuum in National University Hospital Emergency Department (ED) will be enrolled along with non-infective controls. Whole blood samples will be separated immediately into plasma and serum for storage at the Tissue Repository. Those who are subsequently admitted to the general ward, high dependency (HD) or intensive care unit (ICU) will have their 2nd and 3rd samples obtained at 24-48 hours and 48-72 hours respectively. The 2nd and 3rd samples will be used as prognostic markers (Objective #2). Patients who are discharged directly from the ED will be tracked for any clinical recurrence of their disease within 28 days to ensure the diagnostic accuracy of the first sample of biomarkers that are extracted.
Samples will be batch-processed via the circulating miRNA profiling workflow comprising of the pre-analytics, analytics, and data processing and analysis phases. This qPCR-based miRNA profiling has much smaller feature to sample ratio thus allowing a global sequential forward selection to optimally combine a host of features with complementary prediction strengths to form the biomarker panel which has the least number of components and the maximized classification power (ROC AUC). Panel robustness measurement using computational generated noises and validation with a larger set of blinded samples will be performed.
The final objective will be assessed by measuring the concentrations of secreted cytokines, chemokines and reactive oxygen species after synthesis and transfection the newly-derived miRNA panel into monocytes and monocytic cell lines.
- Conditions
- Sepsis
- Keywords
- Sepsis, MicroRNAs, Diagnosis, Prognosis
- Medical subject headings
- Sepsis, Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold changes of miRNA expression
Fold changes of differentially-expressed miRNA in log2 scale in comparison to the severity of sepsis (control vs. sepsis vs. septic shock) and adjudicated requirement for hospitalization (yes vs. no)
Measured: 3 years
Secondary outcomes (1)
MiRNA panel test performance metrics
Sensitivity, specificity and likelihood ratios of capability of miRNA panel to distinguish different severity of sepsis (i.e. requirement for inpatient management) and against standard clinical parameters, C-reactive protein, procalcitonin, and inflammatory cytokines (interleukin-6, interleukin-8).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study startSep 2013
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National University of Singapore, MiRXES Pte Ltd, A*Star
- Responsible party
- Principal investigator, Emergency, National University Hospital, Singapore
- Investigators
- Win Sen Kuan, MBBS, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544490
- Sponsor's protocol ID
- TA/0029/2014
- Acronym
- miRNA-Sepsis
- Status last verified
- Mar 2019
- First submitted
- 29 Aug 2015
- Last updated
- 13 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Circulating Micro-RNA Biomarkers for the Early Diagnosis and Prognosis of Sepsis
- ClinicalTrials.gov ID
- NCT02544490
- Acronym / sponsor ID
- miRNA-Sepsis / TA/0029/2014
- Conditions
- Sepsis
- Keywords
- Sepsis, MicroRNAs, Diagnosis, Prognosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 450 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National University of Singapore, MiRXES Pte Ltd, A*Star
- Study start
- Sep 2013 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 9 Sep 2015 (estimated)
- 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.
The objectives are to:
- derive and validate a panel of miRNAs that are consistently differentially expressed in the plasma of patients with and without sepsis
- investigate the prognostic and predictive values of the panel of miRNAs to guide treatment
- investigate the roles of these differentially-expressed circulating miRNAs in immune modulation during sepsis
The methodology involves sampling of blood from controls and subjects in the sepsis continuum at their earliest presentation in the emergency department longitudinally to hospitalization. The investigators will develop panels of miRNAs that are specific to early and late stages of sepsis, and correlate clinical, biochemical and microbiological outcomes with these miRNAs.
Detailed description
Prospective observational cohort of patients along the entire sepsis continuum in National University Hospital Emergency Department (ED) will be enrolled along with non-infective controls. Whole blood samples will be separated immediately into plasma and serum for storage at the Tissue Repository. Those who are subsequently admitted to the general ward, high dependency (HD) or intensive care unit (ICU) will have their 2nd and 3rd samples obtained at 24-48 hours and 48-72 hours respectively. The 2nd and 3rd samples will be used as prognostic markers (Objective #2). Patients who are discharged directly from the ED will be tracked for any clinical recurrence of their disease within 28 days to ensure the diagnostic accuracy of the first sample of biomarkers that are extracted.
Samples will be batch-processed via the circulating miRNA profiling workflow comprising of the pre-analytics, analytics, and data processing and analysis phases. This qPCR-based miRNA profiling has much smaller feature to sample ratio thus allowing a global sequential forward selection to optimally combine a host of features with complementary prediction strengths to form the biomarker panel which has the least number of components and the maximized classification power (ROC AUC). Panel robustness measurement using computational generated noises and validation with a larger set of blinded samples will be performed.
The final objective will be assessed by measuring the concentrations of secreted cytokines, chemokines and reactive oxygen species after synthesis and transfection the newly-derived miRNA panel into monocytes and monocytic cell lines.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This research project will be a prospective observational cohort study of controls without infection and patients along the entire sepsis continuum the Emergency Department (ED). Admitted patients will be followed-up in the inpatient units including the intensive care unit (ICU) and general wards. Healthy controls and those with systemic inflammatory response syndrome (SIRS) but without evidence of infection will also be recruited to demonstrate differentiation of biomarkers for early diagnosis. The reference standards for infection and sepsis will be positive cultures (e.g. from blood, urine, endotracheal tube, sputum) and final discharge diagnoses.
Key inclusion criteria (4 listed)
- Adults 21 years and above
- Has condition unrelated to any infective cause
- Adults 21 years and above
- Clinical/radiological suspicion or confirmation of infection
Key exclusion criteria (12 listed)
- Underlying chronic inflammatory condition (e.g. inflammatory bowel disease)
- Underlying autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus)
- Pre-existent immunological disorder
- Age below 21 years
- Prisoners
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Fold changes of miRNA expression
Time frame: 3 years
Fold changes of differentially-expressed miRNA in log2 scale in comparison to the severity of sepsis (control vs. sepsis vs. septic shock) and adjudicated requirement for hospitalization (yes vs. no)
1 secondary outcome
MiRNA panel test performance metrics
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2019.
Related trials for Sepsis
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Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
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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.
Win Sen Kuan, MBBS principal investigator
National University Hospital, Singapore
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 Sepsis, run by National University Hospital, Singapore at 1 site in Singapore.
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 4 inclusion and 12 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: finished, as of the sponsor's last update on 13 Mar 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 Singapore. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold changes of miRNA expression (time frame: 3 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 13 Mar 2019.