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

NCT05290454 | Unknown

• 1 other identifier: Wang Hao Qilu
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Severe Acute Respiratory Infection; Community-acquired Pneumonia; Respiratory Tract Infections; Pneumonia; Infections

Keywords

Metagenomic next generation sequencing; Community-acquired Pneumonia; Severe community acquired pneumonia; Conventional microbiology diagnosis technology; Antimicrobial therapy; Pneumonia; Respiratory Tract Infections

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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).

  at 28-day and 90-day after randomization

Secondary Outcomes (5)

• days from randomization to initiation of definitive antimicrobial treatment

  during 28 days after randomization

• overall antimicrobial agent use and cost

  at 28-day and 90-day after randomization

• length of ICU stay

  at 28-day and 90-day after randomization

• 28- and 90-day all-cause mortality

  at 28-day and 90-day after randomization

• Clinical cure rate

  at 28-day and 90-day after randomization

Study Arms (2)

mNGS-guided treatment group

EXPERIMENTAL

In 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.

Other: mNGS-guided treatment

Conventional treatment group

NO INTERVENTION

In 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.

Interventions

mNGS-guided treatment OTHER

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.

mNGS-guided treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead
• Jinan Central Hospital: collaborator

Study Sites (1)

Qilu Hospital of Shandong university

Jinan, Shandong, 250000, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 35983331 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Respiratory Tract Infections; Pneumonia; Infections

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Respiratory Tract Diseases; Lung Diseases

Study Officials

• Wang Hao associate professor

  Qilu Hospital of Shandong University

  STUDY DIRECTOR

Central Study Contacts

Wang Hao associate professor

CONTACT

18560081013; wanghao34@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 22, 2022
• Study Start: August 19, 2022
• Primary Completion: June 1, 2024
• Study Completion: September 1, 2024
• Last Updated: January 31, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Study protocol and ICF will be shared with other researchers when start this trial for five years.
• Access Criteria: Ever researchers can access our study protocol and ICF from the web of clinical trials.gov.

Locations

CN (1)