Gut Microbiota2022-11-09NCT05628493
Gut Microbiota Analysis in IAI Patients With Sepsis-associated Liver Dysfunction
An observational study of Gut Microbiota and Intra-abdominal Infections, run by Chinese Medical Association at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gut Microbiota, Intra-abdominal Infections, Acute Gastrointestinal Injury
- What is being tested?
- Gut microbiota Analysis
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 3 Jan 2022to 14 Sep 2022
- How long will I take part?
- 28 Days
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients diagnosed with intra-abdominal infection (IAI). IAI was diagnosed according to the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated inflammatory indicators in peripheral blood and positive culture of intra-abdominal specimens.
Who may be able to join
- Adult patients (≥18 years)
- Diagnosed as Intra-abdominal infections (IAH)
- Diagnosed as sepsis 3.0
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the detailed description
A retrospective cohort study was conducted involving sepsis patients with IAI treated in ICU department of Nanjing Drum Tower Hospital between April 2020 to April 2020. Adult patients (≥18 years) with IAI who met the criteria for sepsis 3.0 were included. The exclusion criteria included: discharged or died within 48 hours after ICU admission; 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; and pregnancy.The following data were collected within 24 hours after ICU admission: demographic Information: age, sex and comorbidity; the score of disease severity: Acute Physiology and Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA) score; the primary site of abdominal infection: upper or lower gastrointestinal tract, pancreas and others; laboratory indicators: white blood cells (WBC), percentage of neutrophils (N%), C-reactive protein (CRP), procalcitonin (PCT), human leukocyte antigen (HLA)-DR. Date during hospitalization were also collected: complications: respiratory failure, septic shock, acute kidney injury (AKI) and AGI; pathogenic bacteria of ascites culture; bacteremia or not; total parenteral nutrition (TPN) was given or not. Prognostic indicators included ICU length of stay (LOS), hospital LOS, ICU mortality, in-hospital mortality, and 28-day mortality were also recorded.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. IAI was diagnosed according to the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated inflammatory indicators in peripheral blood and positive culture of intra-abdominal specimens. Sepsis 3.0 and septic shock were diagnosed according to Third International Consensus Definition for Sepsis and Septic Shock in 2016. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. AGI diagnosis and grading are based on the ESICM recommendations in 2012.To further clarify the relationship between gut microbiota and SALD, we conducted a prospective observational study between April 2020 to April 2020 in our center. Eligible patients must fulfill the same criteria as above. Other exclusion criteria also include: with expected ICU LOS < 1 week; had participated in any other clinical trial; underwent enterostomy surgery; had chronic inflammatory bowel disease. 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. Moreover, fecal samples were collected per patient on days 1,3 and 7 after ICU admission. Other data collection and the definition of related diseases are the same as the above.
- Conditions
- Gut Microbiota, Intra-abdominal Infections, Acute Gastrointestinal Injury, Sepsis-associated Liver Dysfunction
- Being tested
- Gut microbiota Analysis
- Medical subject headings
- Intraabdominal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gut microbiota AnalysisBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Behavioral: Gut microbiota Analysis | |
| The SALD group | The patient's maximum values of ALT, AST, or TBIL during hospitalization reached any of the SALD criteria. Receives: Behavioral: Gut microbiota Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
28day-mortality
Measured: Day28 after enrollment
Secondary outcomes (2)
Gastrointestinal function
acute gastrointestinal injury (AGI)
Measured: through study completion, an average of 7 days
Gut microbiota
analysis of gut microbiota by 16S rRNA sequencing
Measured: days 1,3 and 7 after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2022
- Study start3 Jan 2022
- Primary completion9 Sep 2022
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gut MicrobiotaStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (actual)
- Target duration
- 28 Days
Sponsor and investigators
- Lead sponsor
- Chinese Medical Association
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Wenkui Yu, Ph.D., Study chair, Study concept and study design
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05628493
- Sponsor's protocol ID
- 2022-11-09
- Acronym
- 2022-11-09
- Status last verified
- Mar 2022
- First submitted
- 9 Nov 2022
- Last updated
- 28 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 26496306Yang 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.
PubMed 34040329
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Microbiota Analysis With Next-generation 16S rRNA Gene Sequencing in IAI Patients With Sepsis-associated Liver Dysfunction
- ClinicalTrials.gov ID
- NCT05628493
- Acronym / sponsor ID
- 2022-11-09 / 2022-11-09
- Conditions
- Gut Microbiota, Intra-abdominal Infections, Acute Gastrointestinal Injury, Sepsis-associated Liver Dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Chinese Medical AssociationResearch network
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- 9 Sep 2022 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 28 Nov 2022 (actual)
- 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.
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.
Detailed description
A retrospective cohort study was conducted involving sepsis patients with IAI treated in ICU department of Nanjing Drum Tower Hospital between April 2020 to April 2020. Adult patients (≥18 years) with IAI who met the criteria for sepsis 3.0 were included. The exclusion criteria included: discharged or died within 48 hours after ICU admission; 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; and pregnancy.The following data were collected within 24 hours after ICU admission: demographic Information: age, sex and comorbidity; the score of disease severity: Acute Physiology and Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA) score; the primary site of abdominal infection: upper or lower gastrointestinal tract, pancreas and others; laboratory indicators: white blood cells (WBC), percentage of neutrophils (N%), C-reactive protein (CRP), procalcitonin (PCT), human leukocyte antigen (HLA)-DR. Date during hospitalization were also collected: complications: respiratory failure, septic shock, acute kidney injury (AKI) and AGI; pathogenic bacteria of ascites culture; bacteremia or not; total parenteral nutrition (TPN) was given or not. Prognostic indicators included ICU length of stay (LOS), hospital LOS, ICU mortality, in-hospital mortality, and 28-day mortality were also recorded.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. IAI was diagnosed according to the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated inflammatory indicators in peripheral blood and positive culture of intra-abdominal specimens. Sepsis 3.0 and septic shock were diagnosed according to Third International Consensus Definition for Sepsis and Septic Shock in 2016. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. AGI diagnosis and grading are based on the ESICM recommendations in 2012.To further clarify the relationship between gut microbiota and SALD, we conducted a prospective observational study between April 2020 to April 2020 in our center. Eligible patients must fulfill the same criteria as above. Other exclusion criteria also include: with expected ICU LOS < 1 week; had participated in any other clinical trial; underwent enterostomy surgery; had chronic inflammatory bowel disease. 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. Moreover, fecal samples were collected per patient on days 1,3 and 7 after ICU admission. Other data collection and the definition of related diseases are the same as the above.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 28 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| The non-SALD group | – | Behavioral: Gut microbiota AnalysisThe 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. |
| The SALD group | – | Behavioral: Gut microbiota AnalysisThe patient's maximum values of ALT, AST, or TBIL during hospitalization reached any of the SALD criteria. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients diagnosed with intra-abdominal infection (IAI). IAI was diagnosed according to the 2005 International Sepsis Forum Consensus Conference. Briefly, the patient present with abdominal symptoms and signs, such as fever (≥38℃), tenderness, rebound pain, etc; elevated inflammatory indicators in peripheral blood and positive culture of intra-abdominal specimens.
Key inclusion criteria (3 listed)
- Adult patients (≥18 years)
- Diagnosed as Intra-abdominal infections (IAH)
- Diagnosed as sepsis 3.0
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gut microbiota Analysisfecal 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. | Behavioural | The SALD group, The non-SALD group |
Primary outcome
mortality
Time frame: Day28 after enrollment
28day-mortality
2 secondary outcomes
Gastrointestinal function
Time frame: through study completion, an average of 7 days
Gut microbiota
Time frame: days 1,3 and 7 after enrollment
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 28 Nov 2022.
- Results publication: PubMed 26496306Guo 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.
- Results publication: PubMed 34040329Yang 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.
- Individual participant dataSharing planned: No
Related trials for Gut Microbiota
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Active, not recruiting
SweetSpot - The Effect of Non-nutritive Sweeteners on Health
Healthy Adult
Enrolling by invitation
Dance-Based Exercise for Cancer-Related Fatigue in Breast Cancer Patients
Breast Neoplasms
Recruiting
The Effect of a Synbiotic on Intestinal Barrier Function and Microbiota Modulation in Middle-aged to Elderly Individuals
Gastrointestinal Microbiome (Focus), Gastrointestinal Symptoms
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.
Wenkui Yu, Ph.D. study chair
Study concept and study design
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 Gut Microbiota and Intra-abdominal Infections, run by Chinese Medical Association 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 3 inclusion and 5 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 28 Nov 2022. 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?
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?
mortality (time frame: Day28 after enrollment). 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 NCT05628493, which also lists 2 linked publications.
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 28 Nov 2022.