mNGS -Guided Antimicrobial Treatment Versus Conventional Antimicrobial Treatment in Early Severe Community-Acquired Pneumonia Among Immunocompromised Patients
Phase: NA
Conditions: Severe Acute Respiratory Infection, Community-acquired Pneumonia, Respiratory Tract Infections, Pneumonia, Infections
Sponsor: Qilu Hospital of Shandong University

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Official title: mNGS -Guided Antimicrobial Treatment Versus Conventional Antimicrobial Treatment in 
Early Severe Community-Acquired Pneumonia among Immunocompromised Patients 
(MATESHIP)  
 
NCT number: 05290454 
 
Document date:19/8/2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study protocol: 
Participants in this study will be randomly allocated to receive mNGS-guided treatment based on both 
results of mNGS and conventional microbiologial tests (CMT) (the experimental arm); or conventional 
treatment only based on the results of CMT (the control arm). 
NO intervention arm: Conventional treatment group 
In the conventional treatment group, clinicians will alter or confirm definitive treatment based on the 
results of CMT.  Participants will undergo CMT using appropriate LRT specimens and other necessary 
specimens (such as blood, pleural fluid, urine, et al.). LRT specimens including endotracheal aspiration, 
bronchoalveolar lavage fluid (BALF), and protected specimen brush, will be obtained within 24 h of 
participants entering the ICU. Blood samples, mid-stream urine, pleural fluid, and other respiratory 
specimens will be collected as soon as possible after admission and, preferably, before antimicrobial 
therapy begins. CMT, including bacterial/fungal stains and cultures, single or multiple RT-PCR, blood 
culture, serum and urine pathogen-specific antigen tests, and serum pathogen-specific antibody tests, 
will be performed according to the consensus 
statement regarding the management of 
immunocompromised patients with CAP and participant conditions. 
Experimental arm: mNGS- guided treatment group 
In the mNGS-guided treatment group, clinicians will alter or confirm definitive treatment based on 
both mNGS and CMT results. Participants will undergo mNGS test using appropriate LRT specimens. 
CMT will also be carried out using appropriate LRT specimens and other necessary specimens (such as 
blood, pleural fluid, urine, et al.), as described for the control group. LRT specimens will be divided into 
aliquots and used for both mNGS tests and CMT. 
Microbiological tests 
Conventional routine microbiological tests will be performed in local laboratories. LRT samples for 
mNGS tests will be transferred to the same professional genomic laboratory independently by 
cold-chain transportation; the genomic laboratory will perform nucleic acid extraction, library 
construction, amplification and sequencing, bioinformatic analysis, and data interpretation. During our 
study period, the professional genomic laboratory will use the consistent mNGS detection protocol 
among the samples of enrolled patients. An independent multidisciplinary panel of senior experts, 
including one infectious disease specialist, an intensivist, and a microbiologist, independently adjudicate 
the causative microorganisms for each patient after reviewing the mNGS results and necessary clinical 
data. 
Participants management 
During hospitalization, participants will receive personalized therapy according to 2019ATS/IDSA 
CAP guidelines, Pneumonia Severity Index (PSI) score, and participants’ conditions. Once participants 
combine with sepsis or septic shock, they will be managed according to International Guidelines for 
Management of Sepsis and Septic Shock 2021. 
Statistical analysis plan: 
(1) Statistical software: All statistical analysis is mainly conducted by SAS 9.4 and R 3.6.0. 
(2) 
1) Full analysis set (FAS): includes cases that have been randomly assigned to the group and have 
follow-up records. Cases missing main evaluation indicators or lost to follow-up will be excluded from 
FAS. 
2) Per-Protocol set (PPS): it is a subset of the ITT data set, that is, all those who complete relevant 
observations according to the requirements of the plan and meet the following conditions, refer to those 

whose compliance is between 80% and 120%, Did not seriously violate the research plan, completed all 
the visits, and completed the CRF, the main evaluation indicators and most other evaluation indicators 
are not missing. 
3) Safety set (SS): All groups who have been randomized and used at least one diagnosis method 
constitute the safety set of this study. All safety information records from the subjects will be evaluated, 
including adverse events, serious adverse events, and abnormal changes in safety indicators that have 
clinical significance. 
4) The efficacy indicators were analyzed by FAS and PPS population respectively. Safety analysis 
adopts SS population analysis. 
5) Stratified analysis: According to the center, stratified analysis is carried out on the 28-day mortality 
rate, and mNGS-guided treatment are explored for related effects on the prognosis of patients with 
severe community-acquired pneumonia. 
（3）Statistical analysis content 
Statistical analysis content 
1). General principles of statistical analysis 
All statistical tests use two-sided tests. After P value is adjusted by FDT, Q value ≤ 0.05 will be 
considered as statistically significant (unless otherwise specified). The description of quantitative 
indicators will calculate the mean, standard deviation, median, minimum, maximum, lower quartile(Q1), 
upper quartile (Q3), and classification indicators to describe the number of cases and percentages of 
each category. The general comparison of the two groups will be analyzed by appropriate methods 
according to the types of indicators. The comparison of quantitative data between groups will be based 
on the data distribution using group t test (homogeneity of variance, normal distribution) or Wilcoxon 
rank sum test, The classification data uses the chi-square test or the exact probability method (if the 
chi-square test is not applicable), and the rank data uses the Wilcoxon rank sum test or the CMH test. 
Kaplan–Meier description, Log-rank test and Cox regression were used for the survival time data of the 
study subjects. The research results of each research center are evaluated by meta-analysis to evaluate 
the heterogeneity and the overall research merger effect. The potential confounding bias (treatment, 
service, management, etc.) of each research center is analyzed using a multi-layered mixed model. 
2). Baseline and demographic characteristics  
Summarize the number of enrollment and make a list of dropped cases. The size of the data set in 
each group, the distribution of cases in each center, the comparison of the total dropout rate, and a 
detailed list of the reasons for termination. 
The demographic characteristics (age, sex, height, body mass index, vital signs, etc.), history of 
allergies, etc. of the subjects were statistically described. According to the numerical characteristics of 
the variables, the t-test/Wilcoxon rank sum test was used to compare the quantitative data of the two 
groups of subjects such as age, height, and body mass index; the chis-quare test/exact probability 
method was used to determine the gender of the subjects, post medical history, allergy history and other 
categorical variables for comparison. 
Analysis of dropped cases: Cases that meet the criteria for dropped cases and the subjects withdrew 
from the study should be included in the dropped case analysis. The total dropout rate between groups 
and the dropout due to adverse events were compared using the chi-square test. 
3). Effectiveness analysis 
(1) Baseline index: Describe the baseline of each curative effect index, refer to general statistical 
methods for the comparison method between groups. A stratified analysis was performed based on the 

center. 
(2) Main efficacy indicators: The relative change in SOFA score from randomization to day 5, day 7, 
day 10, or the day of ICU discharge/death; and the consumption of antimicrobial agents during ICU stay 
(expressed as defined daily doses). Simultaneous FAS analysis and PPS analysis. 
(3) Secondary curative effect index 
①days from randomization to initiation of definitive antimicrobial treatment 
②overall antimicrobial agent use and cost; 
③total cost of hospitalization; 
④length of ICU stay; 
⑤28- and 90-day mortality; and clinical cure rate. 
For all the outcome indicators, first conduct independent evaluation in each research center in 
accordance with general principles. Then meta-analyze the research results of each research center. 
Assess the heterogeneity and the combined effect of the overall study. Finally, a multivariate stratified 
mixed model was used to adjust the potential bias.