Trial document




drksid header

  DRKS00011159

Trial Description

start of 1:1-Block title

Title

Therapeutic drug monitoring-based dose optimisation of piperacillin in patients with severe sepsis or septic shock to investigate effects on organ functions and survival: a prospective, multicenter, randomized controlled trial

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

Trial Acronym

Target

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

URL of the Trial

[---]*

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

Brief Summary in Lay Language

Antibiotic therapy is one of the most important measures in sepsis treatment. Increasing evidence indicates that antibiotic dosing in critically ill patients is inadequate with fixed-dose regimens. Hence, the primary study goal is to investigate whether a daily therapeutic drug monitoring (TDM) - based dose optimization of piperacillin positively affects outcome in patients with severe sepsis or septic shock.

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

Brief Summary in Scientific Language

Administration of antibiotics active against the infecting organism is a cornerstone of effective sepsis management. Management is however complicated by increasing antimicrobial resistance with shortage of new antimicrobial substances. Given the paucity of new antibacterial agents to optimize antimicrobial use and bring out the best of the currently available agents is indispensable. Increasing evidence indicates however that antibiotic dosing in critically ill patients is inadequate with fixed-dose regimens. Pharmacokinetic (PK) and pharmacodynamic (PD) studies during pharmaceutical registration trials are usually conducted in healthy, normal weighted young adults in most instances. However, critically ill patients have a gross physiological derangement, which profoundly impacts PK. Patients with sepsis are known to become hyperdynamic, causing increased clearance of ß-lactams; end-organ dysfunction can lead to impaired drug clearances and capillary leak syndrome results in increased interstitial fluid volumes. Inadequate concentrations, however, negatively affect infection-related patient outcomes and promote the development of antibiotic resistance. Methods to optimize administration of ß-lactam antibiotics in these patients are urgently required. The primary study goal is to investigate whether an
optimisation of antimicrobial therapy by individual dose adjustment of the test substance Piperacillin has a beneficial impact on organ function in severe sepsis or septic shock and whether it is superiour to dosage following prescribing information. This should be examined on the basis of global morbidity measurement (mean total SOFA-score).

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00011159
  •   2016/10/10
  •   [---]*
  •   yes
  •   Approved
  •   4825-06/16, 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

  •   2016-000136-17 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   R65.1 -  Systemic Inflammatory Response Syndrome of infectious origin with organ failure
  •   R57.2 -  Septic shock
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Daily measurement of piperacillin blood concentration with individual dosing based on the minimal inhibitory concentration of the infecting organism beginning on 1st day after randomization

    optional: Measurement of the blood concentration of piperacillin and individual drug dosage already on day of randomisation (day 0)

    duration of therapy with piperacillin/tazobactam is at the discretion of the treating physician, intervention (TDM + dose adjustment) for a maximum of 10 days

  •   standard piperacillin/tazobactam therapy, dosing based on summary of product characteristics
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

It should be investigated whether TDM-based piperacillin therapy results in a benefit regarding patient`s organ function.

primary Endpoint: mean total SOFA (Sequential Organ Failure Assessment) Score – from 1st day after randomization until ICU discharge or death, but only until day 10 after randomization

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

Secondary Outcome

• SOFA-Subscores
• 28-day mortality
• duration and cumulative dosage of antibiotic therapy
• number of dose adjustment / therapy cycle
• days without antibiotic, maximum day 14
• Length of ICU stay, maximum day 28
• Length of hospital stay, maximum day 28
• days without vasopressor, maximum day 14
• days without renal replacement therapy until day 28
• days without mechanical ventilation until day 28
• safety (side effects)
• antibiotic therapy costs

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

Recruitment

  •   Actual
  •   2017/01/26
  •   276
  •   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

• Patients with severe sepsis or septic shock
• onset of severe sepsis or septic shock not longer than 24 hours prior
to randomization
• Antimicrobial therapy with piperacillin planned or started
• age ≥18 years
• written informed consent of the patient or legal representative

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

Exclusion Criteria

• pregnant or breast-feeding women
• anamnestic known hypersensitivity against beta-lactam antibiotics or another part of the investigational medicinal product
• previous treatment with piperacillin (in combination with tazobactam) > 24 hours before randomization
• participation in another interventional clinical trial
• previous participation (TARGET)
• limits of therapy or cessation
• impaired liver function (Child-Pugh C)
• life expectancy < 28 day due to accompanying illnesses
• piperacillin-measurement impossible within 24 hours after randomization

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

Addresses

  • start of 1:1-Block address primary-sponsor
    • Friedrich-Schiller-Universität Jena
    • Postfach
    • 07737  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 other
    • Integriertes Forschungs- und Behandlungszentrum (IFB) SepsisCenter for Sepsis Control and Care (CSCC)
    • Erlanger Allee 101, 07747 Jena
    • Germany
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • Integriertes Forschungs- und Behandlungszentrum Sepsis undSepsisfolgen (CSCC) Zentrum für Infektionsmedizin und Krankenhaushygiene Universitätsklinikum Jena
    • Mr.  Dr. med.  Stefan  Hagel 
    • Erlanger Allee 101
    • 07747  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
    • Integriertes Forschungs- und Behandlungszentrum Sepsis und Sepsisfolgen (CSCC) Zentrum für Infektionsmedizin undKrankenhaushygiene Universitätsklinikum Jena
    • Mr.  Dr. med.  Stefan  Hagel 
    • Erlanger Allee 101
    • 07747  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 Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • 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 ongoing
  •   [---]*
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.