Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00000631

Trial Description

start of 1:1-Block title

Title

Prognostic and Diagnostic Relevance of Bacterial DNA Detection in Patients with Liver Cirrhosis and Ascites at Risk for Spontaneous Bacterial Peritonitis (ACTION) - a prospective multicenter Study

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

ACTION

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

http://www.cscc.uniklinikum-jena.de/cscc/en/Research/Klinische+Forschung/ACTION.html

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Ascites is an abnormal accumulation of fluid in the abdomen that often occurs in patients with liver cirrhosis, the end-stage of chronic liver disease. The spontaneous infection of ascites (spontaneous bacterial peritonitis) is a severe complication in patients with liver cirrhosis that is associated with a high mortality despite antibiotic and supportive treatment. To diagnose an infection of the ascitic fluid, an abdominal tap (paracentesis) is necessary to collect and analyze ascitic fluid, especially in patients with abdominal discomfort, renal failure, elevated white blood cell count, acidosis, and mental alterations (hepatic encephalopathy). Bacterial cultures from ascitic fluid often fail to identify bacteria that have caused spontaneous bacterial peritonitis. With molecular genetic methods it is possible to identify constituent parts of bacteria such as bacterial genetic information (DNA).
There is evidence that patients with liver cirrhosis in the absence of infection that are positive for bacterial DNA have a worse prognosis than patients without bacterial DNA in ascites. In this study we will assess whether patients with liver cirrhosis and signs of infection have a shorter survival when bacterial DNA was detected. Additionally, we will determine conditions that are associated with the translocation of bacterial parts from the gut to blood and ascites in these patients.
For this study a sample of blood and ascitic fluid is necessary. Abdominal tap is a safe procedure with a complication rate of less than 2 per cent and will be performed according to current guidelines. Approximately 100 mL of ascitic fluid are necessary for the analysis of bacterial components, inflammatory cells, and markers of infection and inflammation. Additionally, approximately 50 mL of blood will be drawn to analyze for bacterial components and markers of infection and inflammation.
Within this study we will also evaluate, wether human genetic variants promote translocation of bacteria and bacterial components from the gut into the ascitic fluid in patients with liver cirrhosis and ascites.
Patients with liver cirrhosis and ascites included in this study will be monitored for survival within 3 months with respect to the presence of bacterial DNA in their ascitic fluid.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

The detection of bacterial DNA in Serum and Ascites has been reported to be an independent predictor of mortality in patients with liver cirrhosis in the absence of infection. However, the relevance and prognostic significance of this marker of bacterial translocation has not been evaluated in cirrhotic patients with systemic inflammatory response syndrome (SIRS), bacterial infections, and variants of spontaneous bacterial peritonitis (SPB) including culture-negative neutrocytic ascites and monomicrobial bacterascites. It is not clear, whether different methods of bacterial DNA detection are equivalent and how they correlate with other surrogate markers of bacterial translocation and endotoxemia. In this multicenter cohort study we will derive risk factors for bacterial translocation and endotoxemia in patients with liver cirrhosis and ascites. To validate the clinical relevance of these findings the primary goal of this study is to determine whether the detection of bacterial DNA is associated with an increased mortality in patients with liver cirrhosis, ascites, and signs of inflammation or infection.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00000631
  •   2010/12/03
  •   [---]*
  •   yes
  •   Approved
  •   2880-08/10, Ethikkommission der Friedrich-Schiller-Universität Jena an der Medizinischen Fakultät
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   K74 -  Fibrosis and cirrhosis of liver
  •   R65 -  [---]*
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Multicenter Arm: Inclusion of patients with liver cirrhosis, ascites, and signs of infection. Analysis of blood and ascites for bacterial DNA, markers of inflammation and endotoxemia, and genetic risk factors.
  •   Validation Arm (monocenter): Inclusion of patients with liver cirrhosis and non-neutrocytic ascites without signs of infection. Analysis of blood and ascites for bacterial DNA, markers of inflammation and endotoxemia, and genetic risk factors.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Non-interventional
  •   Observational study
  •   Other
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Diagnostic
  •   Other
  •   N/A
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

90-day mortality of hospitalized patients with liver cirrhosis, ascites, and signs of infection with respect to positive bacterial DNA result in ascitic fluid and in blood

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

-­ In-hospital mortality with respect to bacterial DNA result
-­ 12-month mortailty with respect to bacterial DNA result
- Correlation of bacterial DNA with markers of inflammation and endotoxemia, stage of liver disease, comorbidities, medical procedures, and genetic risk alleles of innate immunity
-­ Diagnostic sensitivity of multiplex PCR for the detection of pathogens in spontaneous bacterial peritonitis

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2010/09/01
  •   220
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Liver cirrhosis defined by clinical, analytical, or histological criteria.
2. Presence of ascites accessible to diagnostic abdominal paracentesis.
3. Age ≥18 Jahre
4. Written informed consent
5. For multicenter arm at least one of the following criteria a. or b.:
a. At least 2 fulfilled criteria of systemic inflammatory response syndrome (SIRS) within the last 24 hours: [i] Body temperature <36 °C or ≥38 °C, [ii] Heart rate ≥90 beats per minute, [iii] Respiratory rate >20 breaths per minute or a PaCO2 less than 32 mm Hg (4.3 kPa), [iv] White blood cell count ≤4,000/mm³ (Leukopenia) or >12,000/mm³ (Leukozytosis) or greater than 10% immature band forms.
b. Bacterial infection within the last 14 days with at least one of the following criteria fulfilled: [i] Positive blood culture result (Septicemia), [ii] Positive urinary culture or leukocyturia ≥20 per high power field (Urinary tract infection), [iii] Pulmonary infiltrates on chest X-ray or CT scan (Pneumonia), [iv] Inflammatory skin lesion (Skin infection), [v] PMN count in ascitic fluid ≥250 /μl (Spontaneous bacterial peritonitis), or [vi] other bacterial infection according to clinical, microbiological, or imaging criteria (e.g. cholangitis)

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Peritoneal carcinomatosis.
2. Secondary peritonitis, i.e. surgically treatable intra-abdominal source of infection including postoperative peritonitis after abdominal surgery.
3. Acute pancreatitis.
4. Tuberculous peritonitis.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Jena, Integriertes Forschungs- und Behandlungszentrum (IFB) Sepsis und Sepsisfolgen Center for Sepsis Control and Care (CSCC)
    • Mr.  Dr. med.  Tony  Bruns 
    • Erlanger Allee 101
    • 07740  Jena
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universitätsklinikum Jena, Integriertes Forschungs- und Behandlungszentrum (IFB) Sepsis und Sepsisfolgen Center for Sepsis Control and Care (CSCC)
    • Mr.  Dr. med.  Tony  Bruns 
    • Erlanger Allee 101
    • 07740  Jena
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address scientific-contact
    • Klinik für Innere Medizin II, Abteilung Gastroenterologie/Hepatologie/Infektiologie, Universitätsklinikum Jena
    • Mr.  Prof. Dr. med.  Andreas  Stallmach 
    • Erlanger Allee 101
    • 07740  Jena
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Klinik für Innere Medizin II Abteilung Gastroenterologie, Hepatologie, Infektiologie Universitätsklinikum Jena
    • Mr.  Dr. med.  Tony  Bruns 
    • Erlanger Allee 101
    • 07740  Jena
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Hannoversche Straße 28-30
    • 10115  Berlin
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up continuing
  •   2012/12/03
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.