AzTrials
AzTrials

Severe Acute Respiratory InfectionMATESHIPNCT05290454

mNGS -Guided Antimicrobial Treatment in Early Severe Community-Acquired Pneumonia Among Immunocompromised Patients

A study testing mNGS-guided treatment in people with Severe Acute Respiratory Infection and Community-acquired Pneumonia, run by Qilu Hospital of Shandong University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Severe Community-acquired pneumonia (SCAP) is a leading global infectious cause of intensive care unit (ICU) admission (approximately 20%-30%), and the primary reason of mortality and morbidity in immunocompromised patients. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
mNGS-guided treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
342 participants
Where
1 siteChina
Study dates
19 Aug 2022to 1 Sep 2024
Phase
Interventional
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Meet the diagnostic criteria of sever community acquired pneumonia (SCAP).
  • SCAP is defined as:
  • With either one major criterion or at least three minor criteria of the IDSA/ATS CAP severity criteria.
  • Admission in ICU.
  • Time from SCAP diagnosis to ICU admission<24 h.
  • Patients with Immunocompromised conditions.
Show all 16Show fewer
  • Immunocompromised conditions are defined as:
  • Use of long-term (>3 months) or high-dose (>0.5 mg/kg/d) steroids.
  • Use of other immunosuppressant drugs.
  • Solid organ transplantation.
  • Solid tumor requiring chemotherapy in the last 5 years.
  • Hematologic malignancy regardless of time since diagnosis and received treatments.
  • Primary immune deficiency.
  • HIV infection with a cluster of differentiation 4 (CD 4) T-lymphocyte count <200 cells/ml or percentage <14%.
  • Laboratory tests show absolute neutrophil count < 1,000 cells/µl on ICU admission.
  • Other immunosuppression status judged by the physicians.

Who cannot join

  • Age<18 years old.
  • Pregnant or lactating women.
  • Those who are expected to die within 72 h.
  • Receiving palliative therapy or supportive treatment only.

Trial locations and contacts

1 site in 1 country.

Wang Hao associate professor contact

18560081013

wanghao34@126.com

China1 site, 1 recruiting
  • Qilu Hospital of Shandong university

    Jinan, Shandong, 250000

    Hao Wang, Doctor, 18560081013, wanghao34@126.com

    Wang Hao associate professor

    Recruiting

Other trials in China

About this study

Official title: mNGS -Guided Antimicrobial Treatment Versus Conventional Antimicrobial Treatment in Early Severe Community-Acquired Pneumonia Among Immunocompromised Patients

Severe Community-acquired pneumonia (SCAP) is a leading global infectious cause of intensive care unit (ICU) admission (approximately 20%-30%), and the primary reason of mortality and morbidity in immunocompromised patients. There is a global increase of patients with distinct immunocompromised conditions due to the advance of cancer treatment, increasing biologics, and immunosuppressants for autoimmune diseases and growing organ transplant recipients, and it has been estimated that patients with immunocompromised conditions account for approximately 35% of all intensive care unit (ICU) admissions. Immunocompromised patients with SCAP have more factors to complicate with sepsis, respiratory failure, acute respiratory distress syndrome, and the mortality rate can be up to 50%. With the aim to apply early accurate antimicrobial therapy to improve clinical prognosis of SCAP patients with immunocompromised conditions, timely identification of pathogen is particularly important. Conventional microbiological diagnostic methods such as standard microbiologic cultures, microscopy, polymerase chain reaction (PCR), respiratory virus multiplex PCR, as well as pathogen-specific antigens and antibody assays, are currently commonly used to detect pathogens, although they have various limitations. However, conventional antimicrobial therapy depends on the results of conventional diagnostic methods, which may delay timely accurate antimicrobial therapy at the initial stage, and the mortality of immunocompromised patients with SCAP may be increased. Metagenomic next-generation sequencing (mNGS), which can determine pathogens more quickly (usually within 24h) and accurately comparing with conventional diagnostic methods by analyzing cell-free nucleic acid fragments of pathogens using appropriate lower respiratory tract (LRT) specimen, is increasingly used in severe respiratory infectious disease, especially among immunocompromised patients. This study aims to determine whether mNGS (using LRT specimen) guided antimicrobial treatment improves clinical prognosis of SCAP patients with immunocompromised conditions when compared with conventional antimicrobial treatment.

Read the detailed description

Severe Community-acquired pneumonia (SCAP) is an emergence infection disease of lung parenchyma that acquired outside of a hospital setting. SCAP is a leading global infectious cause of intensive care unit (ICU) admission (approximately 20%-30%), and the primary reason of mortality and morbidity in immunocompromised patients. There is a global increase of patients with distinct immunocompromised conditions due to the advance of cancer treatment, increasing biologics, and immunosuppressants for autoimmune diseases and growing organ transplant recipients, and it has been estimated that patients with immunocompromised conditions account for approximately 35% of all intensive care unit (ICU) admissions. Immunocompromised patients, who always at risk of mixed and unusual pathogens infection, have more factors to complicate with sepsis, respiratory failure, acute respiratory distress syndrome, and the mortality rate can be up to 50%. Moreover, the outcomes in immunocompromised patients with SCAP not only related to disease severity but also related to delays initiation of receiving appropriate therapy. 2019American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) community-acquired pneumonia (CAP) guideline recommends that administering appropriate antimicrobials as soon as possible is the most effective measure to improve clinical prognosis and reduce mortality rate for SCAP patients. Therefore, timely identification of pathogenic microorganisms is particularly crucial for antimicrobial treatment in immunocompromised patients with SCAP.

Conventional microbiology diagnostic methods, such as standard microbiologic cultures, microscopy, polymerase chain reaction (PCR), respiratory virus multiplex PCR, as well as pathogen-specific antigens and antibody assays, are associated with relevant limitations: (1) long culture cycle and low positive rate; (2) usually only one pathogen can be detected at a time; (3) inability to detect fastidious or difficult culture organisms; (4) pathogen antibody-based testing may be unreliable in immunocompromised patients who are unable to mount antibody responses. Conventional diagnostic methods make big challenge for pathogens diagnosis of SCAP among immunocompromised patients due to above limitations and the complicated causative microorganisms. However, conventional antimicrobial therapy based on the results of conventional microbiology diagnostic techniques, which may delay timely accurate antimicrobial therapy at the initial stage, and the mortality of immunocompromised patients with SCAP may be increased. Metagenomic next-generation sequencing (mNGS), which can quickly (usually within 24h) detect a wide array of bacteria, viruses and fungi in an unbiased manner at the same time by analyzing cell-free nucleic acid (DNA) fragments of pathogens using appropriate lower respiratory tract (LRT) specimen, is increasingly used in severe infectious disease, especially among immunocompromised patients. This study speculates that mNGS (using LRT specimen) can guide early and accurate antimicrobial treatment for immunocompromised patients with SCAP. This multi-center, opening, randomized, controlled trail will enroll SCAP patients with immunocompromised conditions to determine whether mNGS-guided antimicrobial treatment improve the clinical prognosis and increase the clinical cure rate. The purpose of this study is to characterize the effect of mNGS-guided antimicrobial treatment for SCAP versus conventional treatment among immunocompromised patients. It is postulated that mNGS-guided antimicrobial treatment for immunocompromised patients with SCAP will improve clinical outcomes among these patients.

Being tested
mNGS-guided treatment
Keywords
Metagenomic next generation sequencing, Community-acquired Pneumonia, Severe community acquired pneumonia, Conventional microbiology diagnosis technology, Antimicrobial therapy, Pneumonia, Respiratory Tract Infections
Medical subject headings
Community-Acquired Pneumonia, Respiratory Tract Infections, Pneumonia, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mNGS-guided treatmentOther

    mNGS detect the causative microorganisms using appropriate lower respiratory tract (LRT) specimen. LRT specimen, such as endotracheal aspiration (ETA), bronchoalveolar lavage fluid (BALF), or protected specimen brush (PSB), will be obtained within 24 hours after the participants entering the ICU. Clinicians apply the definitive treatment based on mNGS results, as well as results of conventional microbiology diagnostic techniques.

Study groups in NCT05290454
Study groupRoleWhat they receive
mNGS-guided treatment groupExperimentalIn mNGS-guided treatment group, participants undergo mNGS, using appropriate lower respiratory tract (LRT) specimen, and conventional microbiological diagnostic tests. LRT specimen, such as endotracheal aspiration (ETA), bronchoalveolar lavage fluid (BALF), or protected specimen brush (PSB), will be obtained within 24 hours after the participants entering the ICU. Conventional microbiology diagnostic techniques will be also applied using appropriate LRT specimens and other necessary specimens (such as blood, pleural fluid, urine, et al.). Clinicians alter or confirm the definitive treatment based on mNGS results, as well as results from conventional microbiology diagnostic techniques.
Receives: Other: mNGS-guided treatment
Conventional treatment groupNo interventionIn conventional treatment group, participants undergo conventional microbiological tests using appropriate LRT specimen, and other necessary specimens (such as blood, pleural fluid, urine, et al.). LRT specimen, such as endotracheal aspiration (ETA), bronchoalveolar lavage fluid (BALF), or protected specimen brush (PSB), will be obtained within 24 hours after the participants entering the ICU. Based on results of conventional microbiology diagnostic techniques, clinicians alter or confirm the definitive treatment of participants.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death

    Relative Changes in sequential organ failure assessment (SOFA) score at day 5,day 7 and day 10,or the day of ICU discharge/death after randomization when compared with day 0. Sequential organ failure assessment (SOFA) score is used to describe quantitatively and as objectively as possible the degree of organ dysfunction/failure over time. We will record the worst value from randomization until day 10 or the day of ICU discharge/death. The score value is among 0-24, and the higher score value means the worse outcome.

    Measured: at day 5, day 7,and day 10 after randomization or the day of ICU discharge/death

  2. the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses)

    The consumption of antimicrobial agent during participants' ICU stay, and the consumption will be calculated by in terms of defined daily doses (DDD) available from the World Health Organization (WHO).

    Measured: at 28-day and 90-day after randomization

Secondary outcomes (5)
  1. days from randomization to initiation of definitive antimicrobial treatment

    The duration from SCAP diagnosis to the first dose of appropriate definitive antibiotic usage.

    Measured: during 28 days after randomization

  2. overall antimicrobial agent use and cost

    The consumption and cost of antimicrobial agent from admission to discharge of hospital or death

    Measured: at 28-day and 90-day after randomization

  3. length of ICU stay

    The duration from admission to discharge of ICU or death.

    Measured: at 28-day and 90-day after randomization

  4. 28- and 90-day all-cause mortality

    Mortality at 28- and 90-day after randomization.

    Measured: at 28-day and 90-day after randomization

  5. Clinical cure rate

    Clinical cure is defined as resolution of clinical signs and symptoms, and no requirement for continue antimicrobial treatment.

    Measured: at 28-day and 90-day after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2022
  2. Study start19 Aug 2022
  3. Primary completion1 Jun 2024 (estimated)
  4. Study completion1 Sep 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
342 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05290454
Sponsor's protocol ID
Wang Hao Qilu
Acronym
MATESHIP
Status last verified
Jan 2023
First submitted
3 Mar 2022
Last updated
31 Jan 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Study protocol and informed consent form will be shared with other researchers when start this trial.

Publications

  • Fan S, Si M, Xu N, Yan M, Pang M, Liu G, Gong J, Wang H. Metagenomic next-generation sequencing-guided antimicrobial treatment versus conventional antimicrobial treatment in early severe community-acquired pneumonia among immunocompromised patients (MATESHIP): A study protocol. Front Microbiol. 2022 Aug 2;13:927842. doi: 10.3389/fmicb.2022.927842. eCollection 2022.

    PubMed 35983331

Questions about this trial

What is this clinical trial studying?

A study testing mNGS-guided treatment in people with Severe Acute Respiratory Infection and Community-acquired Pneumonia, run by Qilu Hospital of Shandong University 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 16 inclusion and 4 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 31 Jan 2023. 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 Wang Hao associate professor (18560081013, wanghao34@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death (time frame: at day 5, day 7,and day 10 after randomization or the day of ICU discharge/death). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05290454, which also lists 1 linked publication.

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 31 Jan 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in