- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05628493
Gut Microbiota Analysis in IAI Patients With Sepsis-associated Liver Dysfunction (2022-11-09)
Gut Microbiota Analysis With Next-generation 16S rRNA Gene Sequencing in IAI Patients With Sepsis-associated Liver Dysfunction
With the rapid development of intensive care medicine, the mortality of patients with sepsis has decreased over the past decade, but it is still the leading cause of death in intensive care unit (ICU). As an important immune and metabolic organ, the liver plays a crucial role in host defense against invading pathogens and endotoxins, as well as maintenance of metabolic and immunological homeostasis. Some studies indicate that sepsis-associated liver dysfunction (SALD) has a substantial impact on the severity and prognosis of sepsis.
Intra-abdominal infections (IAI) are the second leading source of infection for sepsis after pneumonia in ICU, and are often related to high morbidity and mortality rates. Studies had found that the incidence of SALD in IAI patients was considerably higher than that of general population with sepsis. Moreover, the incidence of acute gastrointestinal injury (AGI) in IAI patients was also much higher than that in sepsis patients with other site infections, as well as the degree of AGI was more serious according to guidelines proposed by the European Society of Intensive Care Medicine (ESICM) in 2012. IAI can directly cause AGI, and a subset of patients usually progress to increased intra-abdominal pressure, which further aggravates AGI.
The pathogenesis of SALD remains unclear so far, and its mechanism is complicated and elusive. Nevertheless, the unique anatomical structure of the liver make it has close association with the gut, growing evidence indicates that the gut microbiota and related metabolites are related to several liver disease. In case of sepsis, gut microbiota disorder and low microbial diversity can cause severe liver injury. An important mechanism for this phenotype is the gut-liver axis, which refers to gut microbial metabolites and nutrients are transported to the liver through the portal vein and hepatic artery to maintain the healthy metabolism of liver.
Therefore, we initially conducted a retrospective study to investigate the relationship between the occurrence of AGI and SALD among IAI patients. Subsequently, a prospective study was performed to analyze and compare the diversity and composition of gut microbiota in IAI patients with or without SALD, respectively, and the dynamic changes in the gut microbiota during the first week after ICU admission were also investigated.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Jiangsu
-
Nanjing, Jiangsu, China, 210008
- Nanjing Drum Tower hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adult patients (≥18 years)
- Diagnosed as Intra-abdominal infections (IAH)
- Diagnosed as sepsis 3.0
Exclusion Criteria:
- Discharged or died within 48 hours afterenrollment
- Known serious chronic liver disease, such as decompensated cirrhosis and end-stage liver cancer
- Hospitalization due to primary hepatobiliary disease, such as trauma, hepatitis, cholelithiasis, etc;
- Other causes of liver injury include: drugs, poisons, etc
- Pregnancy.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
The non-SALD group
The patient did not meet the SALD diagnosis during the study observation period.
SALD was diagnosed when the level of serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1000IU/L, or total bilirubin (TBIL) level >3mg/dL during hospitalization.
|
fecal samples were collected per patient on days 1,3 and 7 after ICU admission.
All eligible patients were given antibiotics therapy, actively control infection source by puncture drainage or surgery if necessary, as well as other supportive therapy to maintain organ function.
|
The SALD group
The patient's maximum values of ALT, AST, or TBIL during hospitalization reached any of the SALD criteria.
|
fecal samples were collected per patient on days 1,3 and 7 after ICU admission.
All eligible patients were given antibiotics therapy, actively control infection source by puncture drainage or surgery if necessary, as well as other supportive therapy to maintain organ function.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
mortality
Time Frame: Day28 after enrollment
|
28day-mortality
|
Day28 after enrollment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gastrointestinal function
Time Frame: through study completion, an average of 7 days
|
acute gastrointestinal injury (AGI)
|
through study completion, an average of 7 days
|
Gut microbiota
Time Frame: days 1,3 and 7 after enrollment
|
analysis of gut microbiota by 16S rRNA sequencing
|
days 1,3 and 7 after enrollment
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Wenkui Yu, Ph.D., Study concept and study design
Publications and helpful links
General Publications
- Guo K, Ren J, Wang G, Gu G, Li G, Wu X, Chen J, Ren H, Hong Z, Wu L, Chen G, Youming D, Li J. Early Liver Dysfunction in Patients With Intra-Abdominal Infections. Medicine (Baltimore). 2015 Oct;94(42):e1782. doi: 10.1097/MD.0000000000001782.
- Yang XJ, Liu D, Ren HY, Zhang XY, Zhang J, Yang XJ. Effects of sepsis and its treatment measures on intestinal flora structure in critical care patients. World J Gastroenterol. 2021 May 21;27(19):2376-2393. doi: 10.3748/wjg.v27.i19.2376.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2022-11-09
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intra-abdominal Infections
-
Iterum Therapeutics, International LimitedCompletedIntra Abdominal InfectionsUnited States, Bulgaria, Estonia, Georgia, Hungary, Latvia, Poland
-
Michael Cohen-WolkowiezThe Emmes Company, LLCCompleted
-
PfizerInnovative Medicines Initiative (IMI) COMBACTE-CARECompletedComplicated Intra-Abdominal Infections, cIAIsSpain, France, Germany
-
Merck Sharp & Dohme LLCCompleted
-
University of BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaCompletedIntra-Abdominal InfectionItaly
-
Kaohsiung Medical University Chung-Ho Memorial...CompletedIntra-abdominal InfectionTaiwan
-
Merck Sharp & Dohme LLCCompletedComplicated Intra-abdominal InfectionsChina
-
Novartis PharmaceuticalsTerminatedIntra-abdominal InfectionsUnited States
-
BayerCompletedInfection, Intra-abdominalChina, Hong Kong, Indonesia, Korea, Republic of, Malaysia, Taiwan
Clinical Trials on Gut microbiota Analysis
-
Xinjiang Medical UniversityCompleted
-
Russian Academy of Medical SciencesRecruitingMelanoma Stage Iii | Melanoma, SkinRussian Federation
-
Herlev HospitalUniversity of ArkansasUnknownMicrobial Colonization | Delirium of Mixed Origin
-
Istituto Ortopedico RizzoliCompleted
-
The Catholic University of KoreaRecruiting
-
Shanghai Jiao Tong University School of MedicineFudan University; Shanghai 10th People's HospitalCompleted
-
University of BolognaActive, not recruitingDiffuse Large B Cell LymphomaItaly
-
Fondazione Don Carlo Gnocchi OnlusUniversity of FlorenceRecruiting
-
Zhujiang HospitalRecruitingSepsis | Septic ShockChina