FC Change From Day 1 to Day 3 Associated With SALD

Liver Dysfunction Clinical Trial

— 2024-04-22  

Official title:

The Dynamic Change of Fecal Calprotectin From Day 1 to Day 3 Was Associated With Sepsis-associated Liver Dysfunction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06403553
• Other study ID #: 2024-04-22
• Status: Completed
• Start date: January 1, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: January 2023
• Source: Chinese Medical Association
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

As defined by sepsis 3.0, sepsis is a clinical syndrome caused by disordered host response to serious infection，leading to multiple organ dysfunction1. Sepsis-associated liver dysfunction (SALD) is one of the most frequently complication in sepsis, possessing high morbidity and mortality2. A close relationship exists between the gut and the liver, and their bidirectional interaction was commonly known as the 'gut-liver' axis3. Systemic inflammation and hypoperfusion play a crucial role in the pathophysiological processes of acute gastrointestinal injury (AGI) in sepsis4. The translocation of bacteria and toxins due to gut barrier injury during AGI can promote the entry of bacteria and their products into the liver through the portal circulation and lymphatic system, leading to the occurrence of SALD. Our previous study found that septic patients with abdominal infections and SALD suffered a higher incidence of AGI when compared with patients without SALD5. Faecal calprotectin (FC) is a convenient, non-invasive biomarker that has a good correlation with gut inflammation6. The FC concentration is proportional to neutrophil migration to the gut and correlates well with fecal leukocyte excretion7. Study found that FC concentrations were significantly higher in septic patients complicated with AGI than those without, and it can be used as an early indicator for the diagnosis of AGI8. However, the relationship between FC concentration and SALD in septic patient is unclear. We conducted a prospective study to explore the potential association between FC concentration and SALD in septic patients. The dynamic changes in the FC concentration from day 1 to 3 after enrollment were also investigated.

Description:

Study participants This was a single-center prospective observational study enrolling consecutive adult patients with sepsis (≥18 years) admitted to Nanjing Drum Tower Hospital between January 2023 to March 2024. The study protocol was approved by the Medical Ethics Committee of local institution (number: 2023-396-03). All patients or their immediate family members provided the informed consent and all study procedures were in line with the Declaration of Helsinki. Exclusion criteria were: 1. had diseases originating in the gastrointestinal tract, such as gastrointestinal malignancies and inflammatory bowel disease (IBD); 2. complicated by severe chronic liver diseases, such as decompensated cirrhosis and advanced liver cancer; 3. hospitalization for primary hepatobiliary disease, such as trauma, hepatitis and hepatic abscess; 4. already diagnosed SALD at enrollment; 5. were discharged or died within 72 hours after enrollment; 6. were pregnant. All eligible patients were treated according to the sepsis 3.0 guidelines, including: control the source of infection, used antibiotic early and other supportive therapies to maintain organ function. Patients were divided into non-SALD and SALD groups according to SALD whether or not diagnosed during intensive care units (ICU) stay. Eligible patients also be excluded if the following occurs during the study period: 1. deviation from the study protocol for any reason; 2. have other causes of liver injury, such as drugs and poisons; 3. diagnosis of SALD within 72 hours after enrollment; 4. patients or their relatives decided to withdraw from the study. Data collection and outcomes The primary study outcome was the FC concentration (<50.00 μg/g), which reflect the severity of gut inflammation. Fecal samples were collected from patients on days 1 and 3 after inclusion using sterile tubes and stored at 4°C, and FC was measured within 48 hours of collection using commercial ELISA (KAPEPKT849, Beijing North Institute of Biotechnology Co.,Ltd., Beijing, China) following the manufacturer's instruction. The following information were collected within the first 24 hours of enrollment, including: demographic characteristics, including age, gender and comorbidity; the sources of infection; disease severity scores, including Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score; complications, including respiratory failure, septic shock, acute kidney injury (AKI), and AGI; inflammatory factors, including interleukin (IL)-1β,IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, interferon (IFN)-α，IFN-γand tumor necrosis factor (TNF); other indicators, including human leukocyte antigen (HLA)-DR, albumin, platelet and D-dimer were also recorded. The following indicators were collected on days 1 and 3 after enrollment: white blood cell (WBC) count, neutrophil count, lymphocyte count, C-reactive protein, procalcitonin and IL-6. Prognostic indicators included ICU length of stay (LOS) and ICU mortality were also recorded. Definitions Sepsis and septic shock were diagnosed based on criteria established by the Sepsis 3.0 guidelines1. SALD was diagnosed when patients meet either of the following two criteria under sepsis condition9: 1. Serum aminotransaminase levels > 800 IU/L, including alanine aminotransferase and aspartate aminotransferase; 2. Total bilirubin > 2 mg/dL. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes clinical practice guidelines10. The diagnosis of AGI was based on the ESICM recommendations in 201211. The term 'FC1' was used to represent the FC concentration on day 1 and 'FC3' on day 3. The term 'ΔFC' was used to represent the concentration of the FC3 minus the concentration of the FC1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• adult patients with sepsis

Exclusion Criteria:

• had diseases originating in the gastrointestinal tract, such as gastrointestinal malignancies and inflammatory bowel disease (IBD);
• complicated by severe chronic liver diseases, such as decompensated cirrhosis and advanced liver cancer;
• hospitalization for primary hepatobiliary disease, such as trauma, hepatitis and hepatic abscess;
• already diagnosed SALD at enrollment;
• were discharged or died within 72 hours after enrollment;
• were pregnant.

Related Conditions & MeSH terms

• Liver Diseases
• Liver Dysfunction

Intervention

Diagnostic Test:
• Fecal Calprotectin
Fecal Calprotectin measurement on days 1and 3

Locations

Country	Name	City	State
China	Drum Tower Hospital	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Medical Association

Country where clinical trial is conducted

China, 

References & Publications (2)

Li J, Ren Y, Gao C, Zhang K, Zheng F, Kang J. Evaluation of Fecal Calprotectin, D-Lactic Acid and Bedside Gastrointestinal Ultrasound Image Data for the Prediction of Acute Gastrointestinal Injury in Sepsis Patients. Front Med Technol. 2021 Nov 1;3:733940 — View Citation

Zhang B, Chen X, He C, Su T, Cao K, Li X, Duan J, Chen M, Zhu Z, Yu W. Acute gastrointestinal injury and altered gut microbiota are related to sepsis-induced cholestasis in patients with intra-abdominal infection: a retrospective and prospective observational study. Front Med (Lausanne). 2023 Jul 27;10:1144786. doi: 10.3389/fmed.2023.1144786. eCollection 2023. Erratum In: Front Med (Lausanne). 2023 Aug 29;10:1280907. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of SALD	whether SALD occurs	30 days after ICU admission
Secondary	mortality	death or not	30 days after ICU admission