Clinical trial NCT03676777: Study Of Bacterial/Fungal Infections in Hospitalized Patients With Liver Cirrhosis in China
Official title: Prospective, Non-interventional, Multicenter Observational Study of Bacterial/Fungal Infections in Hospitalized Patients With Liver Cirrhosis in China
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cirrhosis
Keywords: Bacterial infection
Fungal infection
Cirrhosis
Multi-drug resistance
Antibiotic treatment
Clinical outcome
Organ failure
Acute-on-chronic liver failure
Decompensated cirrhosis
Complications of cirrhosis
Acute kidney injury
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2018-09-19
Enrollment: 1232
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hospitalized patients with cirrhosis evaluated in a dedicated and organized tertiary-care center (Liver Unit, Department of infectious diseases, Department of Gastroenterology, emergency department) across China.

Brief summary: This is a national, investigator-initiated, multicenter, prospective, observational, web-based registry in hospitalized patients with cirrhosis across China.

The overarching aim of this study is to investigate the epidemiology and clinical impact of bacterial/fungal infections in hospitalized patients with liver cirrhosis in China within the collaborative network. We also aimed to build up the national prospective cohort of hospitalized cirrhosis in China to stand in the future for the backbone of various research programs focused on infection, other complications of cirrhosis, organ failure, the ACLF syndrome, end-stage liver disease and beyond.

Detailed description: Patients with cirrhosis are prone to infections due to the abnormal bacterial translocation and immune dysfunction. Infections are more common when these patients are admitted into the hospital. Infections are life-threatening complications of cirrhosis which can precipitate hepatic encephalopathy, acute kidney injury, and the acute-on-chronic liver failure (ACLF) syndrome. The survival rate is significantly decreased once infections set in, especially when the first-line empirical antibiotic therapy is insufficient or inappropriate. Moreover, the prevalence of multi-drug-resistant organism (MDRO) is naturally increasing across the world due to the overuse of antibiotics. Patients with cirrhosis, especially those at the decompensated stage are at high risk of developing MDRO due to recurrent hospitalizations and repeatedly exposed to antibiotics either for treatment or prophylactic purposes. Empiric antibiotic therapy could be very difficult without understanding the profile of antibiotic resistance and could be varied significantly among different areas.

The issue of infection in patients with cirrhosis has been recently highlighted by International Club of Ascites with its "GLOBAL" study (ILC2018, GS-001) showing that the global prevalence of MDRO across the world was 34% (95% CI=31-37%). The prevalence of MDRO varies across the world with the highest in India followed by South America and other Asian countries. The source of acquisition (Community acquire, health-care related or nosocomial origin), site of infection (Spontaneous bacterial peritonitis, urinary tract, blood, respiratory tract, etc.) and category of the organism (Gram negative or positive) had an influence on the prevalence of MDRO and response to empirical antibiotic treatment. The results highlight the need to develop different empirical antibiotic strategies across different continents and countries, although China was not included in this study. Epidemiology data and investigation on the role of bacterial/fungal infection in patients with cirrhosis from China is therefore urgently needed.

The overarching aim of this study is to investigate the epidemiology and clinical impact of bacterial/fungal infections in hospitalized patients with liver cirrhosis in China within the collaborative network. We also aimed to build up the national prospective cohort of hospitalized cirrhosis in China to stand in the future for the backbone of various research programs focused on infection, other complications of cirrhosis, organ failure, the ACLF syndrome, end-stage liver disease and beyond.

Eligibility criteria: Inclusion Criteria:

* Inpatient with cirrhosis as confirmed either by the histological scoring system, imaging technique (abdominal Ultrasound, CT or MRI), endoscopic findings or a combination of biochemical and clinical manifestation.
* Admitted for at least one of the following reasons:

  1. Bacterial infection/fungal infection
  2. Overt Ascites (Grade II-III)
  3. Gastrointestinal bleeding
  4. Hepatic encephalopathy
  5. Jaundice (Total bilirubin ≥5 mg/dL) with coagulation dysfunction (INR ≥1.5)

Exclusion Criteria:

* 1. Age below 16 or over 80 years
* 2. Lactation/ Pregnancy women
* 3. HIV infection
* 4. Admitted for scheduled procedures (e.g., band ligation, splenectomy, transjugular intrahepatic portosystemic shunting, liver biopsy) or re-examination or multidisciplinary consultation)
* 5. Hepatocellular carcinoma (HCC) outside Milan criteria or other disseminated malignancies
* 6. Previous liver transplantation
* 7. With previously known severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease; severe chronic pulmonary disease, psychiatric disorders)
* 8. Taking immunosuppressive or anticoagulation drugs for the treatment of extra-hepatic disease.
* 9. Patient' s refusal to participation
* 10. Failure to provide prior informed consent or with documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent

Primary outcomes:
measure: 28-day transplantation-free Survival
timeFrame: From admission to 28-day post-admission
Secondary outcomes:
measure: Characteristics of bacterial/fungal infection including the prevalence of infection, the source of acquisition, type of infection, multidrug resistance rate, antibiotic treatment efficiency and efficacy in relation to disease course and outcome
timeFrame: From admission to discharge, an average of 28-day
measure: Association between bacterial/fungal infection between other complications of cirrhosis、organ failure、AKI or ACLF.
timeFrame: From admission to discharge, an average of 28-day
measure: Difference in type of organ failure between bacterial/fungal infection and other precipitating events.
timeFrame: From admission to discharge, an average of 28-day
measure: ACLF and each sub-type organ failure development at 28-day
timeFrame: From admission to discharge, an average of 28-day
measure: Transplantation-free Survival at 90-day
timeFrame: From admission to 90 day post-admission
measure: Overall survival at 28-、90-day
timeFrame: From admission to 90 day post-admission
measure: Readmission and further decompensations rate at 90-day post discharge
timeFrame: From admission to 90 day post-discharge
Other outcomes:
Locations:
city: Hefei
country: China
facility: First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Department of Critical Care Medicine of Liver Disease, Beijing You'an Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Department of severe Liver Diseases, Fuzhou Municipal Infectious Disease Hospital, Mengchao Hepatobiliary Hospital of Fujian Medical University,
state: Fujian
city: Xiamen
country: China
facility: Xiamen Hospital of Traditional Chinese Medicine
state: Fujian
city: Lanzhou
country: China
facility: Department of Infectious Disease, The First Hospital of Lanzhou University
state: Gansu
city: Lanzhou
country: China
facility: The First People's Hospital of Lanzhou City
state: Gansu
city: Guilin
country: China
facility: The Third People's Hospital of Guilin
state: Guangxi
city: Nanning
country: China
facility: Department of Infectious Disease, The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University
state: Hebei
city: Changzhou
country: China
facility: Department of Liver Diseases, The Third People's Hospital of Changzhou
state: Jiangsu
city: Suzhou
country: China
facility: Department of Infectious Diseases, the Fifth People's Hospital of Suzhou
state: Jiangsu
city: Wuxi
country: China
facility: The Fifth People's Hospital of Wuxi, Affiliated to Jiangnan University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Shanghai
country: China
facility: Department of Hepatology and Infection, Tongren Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Xi'an
country: China
facility: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University.
state: Shanxi
city: Hangzhou
country: China
facility: Department of Infectious Diseases, Zhejiang Provincial People's Hospital
state: Zhejiang
city: Jiaxing
country: China
facility: The first Hospital of Jiaxing
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo no.2 Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: First Affiliated Hospital, Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Ruijin Hospital
name: Qing Xie, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: